TWENTIETH INTERNATIONAL CONFERENCE ON ADVANCES IN CRITICAL CARE NEPHROLOGY February 16-19, 2016 Manchester Grand Hyatt San Diego, California

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2 AKI&CRRT 2016 TWENTIETH INTERNATIONAL CONFERENCE ON ADVANCES IN CRITICAL CARE NEPHROLOGY February 16-19, 2016 Manchester Grand Hyatt San Diego, California TABLE OF CONTENTS CME Information and Faculty Disclosure Statements 2 Organizing Committee and Faculty List 5 Acknowledgements 9 Abstract Index 23 Schedule Pages (guides to presentation outlines if available) ELECTIVE WORKSHOPS - PW1, PW2 (Electives, CME Available) TUESDAY, February 16 PW1: Changing Paradigms in Acute Kidney Injury: From Mechanisms to Management 10 PW2: Practice Based Learning in CRRT: The Science and the Art 11 PLENARY SESSIONS - Mini-Symposia (CME Available for Plenary 1-6) WEDNESDAY, February 17 SESSION I: PATIENT CHARACTERISTICS Plenary 1 1:10pm-3:30pm 12 Plenary 2 4:00pm-6:00pm 13 THURSDAY, February 18 SESSION II: CONTROVERSIES IN CRITICAL CARE NEPHROLOGY Plenary 3 10:00am-12:15pm 14 SESSION III: EMERGING CONCEPTS IN AKI AND RRT Plenary 4 1:45pm-3:30pm 15 Plenary 5 4:00pm-6:00pm 16 FRIDAY, February 19 SESSION IV: IMPROVING OUTCOMES IN AKI Plenary 6 8:00am-10:40am 17 STANDARD WORKSHOPS (CME Available) WEDNESDAY, February 17 Workshop Group 1-8:00am-9:30am - A01, B02, C03, D04, E05, F06, G07 19 Workshop Group 2-10:00am-11:30am - A08, B09, C10, D11, E12, F13, G14 20 THURSDAY, February 19 Workshop Group 3-8:00am-9:30am - A15, B16, C17, D18, E19, F20, G21 21 MEET THE EXPERT BREAKFAST (Electives, CME Available) WEDNESDAY, February 17 ME1 - How do I Manage Patients with High Risk for AKI in the ICU - 7:00am-8:00am 22 ME2 - How do I Assess and Follow Up Patients After an Episode of AKI - 7:00am-8:00am 22 THURSDAY, February 19 ME3 - How I Assess Patients in the ICU and My Approach to Oliguria - 7:00am-8:00am 22 ME4 - How I Use the KDIGO AKI Guidelines to Manage Patients - 7:00am-8:00am 22 LUNCH SYMPOSIA WEDNESDAY, February 17-11:30am-1:00pm A. New Kids on the Block: Emerging Biomarkers in AKI, CKD and Cardiorenal Syndrome (CME Available) 22 B. Fluid Management of the Critically Ill Patient: Crystalloids, Colloids and Blood Products (CME Available) 22 C. Novel Approaches for Recognition and Mgmt of Life Threatening Complications of AKI & CKD (CME Available) 22 THURSDAY, February 19-12:15pm-1:45pm D. Injury Matters: The Role of Risk Assessment and Early Intervention in AKI (CME Available) 22 E. Improving Outcomes in AKI and CRRT: Does Quality Matter? (CME Available) 22 F. Winning The War Against Critical Illness: Role of Post-ICU Quality of Life (CME Available) 22 1

3 CME AKI&CRRT 2016 CONFERENCE DESCRIPTION AND LEARNER OBJECTIVES The CRRT conference provides a comprehensive review of advances in clinical care, research and technology in critical care medicine with a focus on the kidney and renal support techniques. The conference is designed to facilitate interdisciplinary interactions among caregivers involved in the management of patients in intensive care units. Physicians, nurses, pharmacists, nutritionists and other allied personnel from industry have opportunities to learn from each other. The conference utilizes a combination of invited lectures; case based small group workshops, debates, hands-on interactive based workshops. Attendees have an opportunity to interact with the faculty through focused panel discussions and symposia. Oral and poster presentations and pre-conference hands-on workshops provide a wide variety of opportunities to earn credits. At the end of this conference attendees should be able to: 1. Describe the recent advances in the pathophysiology and management of critically ill patients with a focus on fluid and drug management of shock, multi-organ failure, infections, liver failure. 2. Discuss the optimal ways to diagnose, treat and follow up patients with acute kidney injury utilizing biomarkers, imaging and lab studies and use educational tools to raise awareness of AKI. 3. Describe the principles and practice of renal replacement techniques including CRRT, IHD and Plasma ACCREDITATION STATEMENT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of The University of California, San Diego School of Medicine and CRRT, Inc. The University of California, San Diego School of Medicine is accredited by the ACCME to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this live activity for a maximum of 29.0 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. BRN: For the purpose of recertification, the American Nurses Credentialing Center accepts AMA PRA Category 1 Credits issued by organizations accredited by the ACCME. For the purpose of relicensure, the California Board of Registered Nursing accepts AMA PRA Category 1 Credits (report up to 29.0 hours of credit and list "CME Category 1" as the provider number). NEEDS ASSESSMENT Several sources of information were utilized to identify the practice gaps prompting this educational conference. These include literature review of multiple publications in Pubmed, publications from the American Society of Nephrology, International Society of Nephrology, published KDIGO and European Best Practice and NICE guidelines and feedback from participants and faculty at prior CRRT conferences and discussions with the organizing committee. TARGET AUDIENCE The CRRT target audience includes: MD/DOs, NP/PA/Nurses, Dieticians, Industry, Pharmacists, Residents and Fellows. Specialties include: Anesthesiology, Cellular & Molecular Medicine, Critical Care, Emergency Medicine, Family & Preventive Medicine, Geriatrics, and Internal Medicine. CULTURAL AND LINGUISTIC COMPETENCY This activity is in compliance with California Assembly Bill 1195 which requires continuing medical education activities with patient care components to include curriculum in the subjects of cultural and linguistic competency. Cultural competency is defined as a set of integrated attitudes, knowledge, and skills that enables health care professionals or organizations to care effectively for patients from diverse cultures, groups, and communities. Linguistic competency is defined as the ability of a physician or surgeon to provide patients who do not speak English or who have limited ability to speak English, direct communication in the patient s primary language. Cultural and linguistic competency was incorporated into the planning of this activity. Additional resources on cultural and linguistic competency and information about AB1195 can be found on the UCSD CME website at CME ACTIVITIES The following Workshops/Symposia, Plenary Sessions and Meet the Expert Sessions qualify for CME Credit: Tuesday Electives PW1 Changing Paradigms in AKI PW2 Practice Based Learning in CRRT, Wednesday MEET THE EXPERT SESSIONS, LUNCH SYMPOSIA - A, B & C GROUP 1 - SIMULTANEOUS STANDARD WORKSHOPS GROUP 2 - SIMULTANEOUS STANDARD WORKSHOPS OPENING SESSION I: PATIENT CHARACTERISTICS 2 Thursday MEET THE EXPERT SESSIONS LUNCH SYMPOSIA - D, E, & F GROUP 3 - SIMULTANEOUS STANDARD WORKSHOPS SESSION II: CONTROVERSIES IN CRITICAL CARE NEPHROLOGY SESSION III: EMERGING CONCEPTS IN AKI AND RRT Friday SESSION IV: IMPROVING OUTCOMES IN AKI

4 FACULTY DISCLOSURES AKI&CRRT 2016 Faculty Disclosure Summary 21 st International Conference on Advances in Critical Care Nephrology AKI & CRRT February 16-19, 2016 It is the policy of the University of California, San Diego School of Medicine and CRRT, Inc to ensure balance, independence, objectivity and scientific rigor. All persons involved in the selection, development and presentation of content are required to disclose any real or apparent conflicts of interest. All conflicts of interest will be resolved prior to an educational activity being delivered to learners through one of the following mechanisms 1) altering the financial relationship with the commercial interest, 2) altering the commercial interest, and/or 3) validating the activity content through independent peer review. All persons are also required to disclose any discussions of off label/unapproved uses of drugs or devices. Persons who refuse or fail to disclose are disqualified from participating in the CME activity. Participants will be asked to evaluate whether the interests reflect a possible bias in the planning or presentation of the activity. This information is used to plan future activities. Speaker Name Name of Commercial Interest Nature of Relevant Relationship David Askenazi, Asst. Prof. BTG, Baxter, AKI Foundation Speaker Linda Awdishu, PharmD, MAS International Serious Adverse Grant, Research Support Effects Consortium Sean Bagshaw, Asst. Prof. Baxter Grants/Research Recipient, Advisor, Emmanuel Burdmann, MD, PhD Abbvie, Baxter Scientific Consulting Lakhmir Chawla, MD Abbvie, Alere, Battelle, NxStage Consulting Medical, La Jolla Pharma, Astute Medical Research Support, Sponsored Research George Washington University Patent UPMC Grants/grants pending NuVox Pharmaceuticals Stock/stock options Noel Gibney, MB, FRCP(C) Baxter Member of Expert Panel Stuart Goldstein, MD AM Pharma, Akebia, Bellco, Consultant La Jolla Pharmaceuticals Baxter-Gambro Hemametrics Otsuka Grant Support, Consultant, Stock Shareholder Consultant/Study Steering Committee Member Michael Joannidis, MD Fresenius Kabi Research Support John Kellum, MD Alere, Baxter, Bard, Fresenius, Consultant, Grants/Research Grifols Astute Medical Consultant, Grants/Research Licensed Technology Jay Koyner, Assist. Prof Abbott, Thrasos, Clinical Trials Astute Consultant, Clinical Trials Pfizer Consultant, Medical Advisory Board NxStage, Satellite Healthcare Research Funding Argutus Medical Patent Alan Maisel, MD Alere, Critical Diagnostics, Consultant Sphingotec Alere, Abbott, Thermofisher Research Alere Speaker Cardero Therapeutics, My Life Diagnostics Co-Founder Ravindra Mehta, MBBS, MD, DM, FACP Abbvie, AM-Pharma, Astute Advisory Board Eli Lilly Baxter, Ferring, Gambro, Consultant Gilead Sciences, ISIS Thrasos Grifols Grant Alexion Focus Group Allocure, Cytopherx, Spectral Clinical Trials Ardea Inc. Advisor or Review Panel Member Fresenius Kabi Speaker, Advisor Bruce Mueller, PharmD,FCCP,FASN Astellas, Theravance Grant Funding NxStage Baxter Speaker Bureau 3 continued

5 FACULTY DISCLOSURES AKI&CRRT 2016 Patrick Murray, MD Abbott Research Grant, Consultant, Speaker Alere, EKF Diagnostics Research Grant AM-Pharma, FAST Diagnostics Scientific Advisory Board Thrasos, Astellas, Pfizer Consultant EMAS Pharma Mitra Nadim Baxter, Consultant Mallinckrodt Pharmaceuticals Eisei Noiri, MD Asahi Kasei Medical, A-Step Research AMED Paul Palevsky, MD Baxter Consultant Stealth Biotheraeputics Advisory Panel Peter Pickkers, Prof. AM Pharma Consultant, Honorarium John Prowle, MD Baxter-Gambro Renal Consultant, Speaker's Honorarium Nikkiso Europe GmbH Development Support Andrew Shaw, MB, FRCA, FFICM, FCC Astute, Baxter, FAST Consultant Thrasos Trial Steering Committee Member Joshua Thurman, MD Alexion Pharmaceuticals Royalty Recipient Ashita Tolwani, MD Baxter-Gambro Consultant, Grant, Patent NxStage Educational Grants James Tumlin, MD Medtronic, Galectin Therapeutics Consultant, Grant Volker Vallon, MD AstraZeneca,Fresenius Grant Boehringer Ingelheim Janssen, Intarcia Therapeutics Consultant Manjeri Venkatachalam, MBBS Astellas Pharma Advisory/Review Panel Member Ron Wald, MD Alere Grant, Honorarium Baxter Grant, Honorarium, Consultant Thrasos Scientific Advisory Board David Ward, MD TerumoBCT Honorarium for Lectures/Consultant Paul Wischmeyer, MD Abbott, Fresenius Kabi Inc, Consultant, Grant, Honorarium Medtronic Baxter Grant, Honorarium Nestle Consultant The following speakers have no relevant financial relationships to disclose: Anupam Agarwal, MD Steven Alexander, MD Amelia Allsteadt, BSN,RN,CNN Simon Atkinson, PhD Ian Baldwin, RN, PhD, ACCCN Rajit Basu, MD Josee Bouchard, MD Vincenzo Cantaluppi, MD Jorge Cerda, MD, FACP, FASN Rajasekara Chakravarthi, MD DNB Rolando Claure-Del Granado, MD Michael Conner, MD Dinna Cruz, MD Andrew Davenport, MD Judy E. Davidson, DNP, RN, FCCM Xiaoqiang Ding, Prof. Kent Doi, MD Zheng Dong, PhD Prasad Devarajan, MD, FAAP Zoltan Endre, Prof Geoffrey Fleming, MD Thomas Golper, MD Patty Graham, RN, MS, CCRN, CS Raymond Harris, MD Hiroyuki Hirasawa, MD Patrick Honoré, MD Eric Hoste, MD, PhD Luis Juncos, MD Patrick Kamath, MD Kianoush B. Kashani, MD Gilbert Kinsey, PharmD, PhD Chris Laing, MD David Leaf, MD, MMSc, FASN Andrew Lewington, MD Eileen Lischer, MA, BSN, RN Etienne Macedo, MD, PhD Isagani Marquez, RN Peter McCullough, MD, MPH Theresa Mottes, RN Noel Oabel, SN, RN, CNN Mark Okusa, Prof Marlies Ostermann, MD William Reeves, MD Claudio Ronco, MD Mitchell Rosner, Assit Prof. Amber Sanchez, MD Miet Schetz, MD, PhD Nick Selby, MD Teri Shell, RN Scott Sutherland, Peds Neph Jordan Symons, MD Jean-Louis Vincent, MD, PhD David Warnock, MD Francis Perry Wilson, MD, MSCE Li Yang, MD Karen Yeates, MD Motoko Yanagita, MD, PhD The CME staff, meeting planners, planning committee and CME committee reviewers do not have any relevant financial relationships to disclose. This educational activity may contain discussion of unlabeled and/or investigational uses of agents that are not approved by the FDA. Please consult the prescribing information for each product. The views and opinions expressed in this activity are those of the faculty and do not necessarily reflect the views of the University of California, San Diego. 4

6 AKI&CRRT 2016 ORGANIZING COMMITTEE CHAIRMAN Ravindra L. Mehta, MBBS, MD, DM, FACP, FRCP(UK) USA Steven R. Alexander, MD Linda Awdishu, PharmD, MAS Jorge Cerda, MD, FACP, FASN Dinna N. Cruz, MD, MPH, FASN Stuart Goldstein, MD Thomas A. Golper, MD Patricia Graham, MS, RN, CCRN, CS John Kellum, MD Eileen Lischer, MA, BSN, RN, CNN Bruce Mueller, PharmD, FCCP Ashita Tolwani, MD David M. Ward, MD, FRCP CANADA Noel Gibney, MD Ron Wald, MD SOUTH AMERICA Emmanuel Burdmann, MD, PhD EUROPE Andrew Davenport, MD, FRCP Patrick Honoré, MD, PhD Claudio Ronco, MD Miet Schetz, MD, PhD JAPAN Kent Doi, MD, PhD, FASN Hiroyuki Hirasawa, MD, PhD AUSTRALIA Zoltan Endre, MD, PhD CHINA Xiaoquing Ding, MD Li Yang, MD INDIA Rajasekara Chakravarthi, MD, DNB AKI&CRRT 2016 FACULTY COURSE DIRECTOR Ravindra L. Mehta, MBBS, MD, DM, FACP Professor of Clinical Medicine University of California, San Diego School of Medicine Associate Chair for Clinical Research, Department of Medicine Director, Clinical Nephrology and Dialysis Programs UCSD Medical Center San Diego, CA USA FACULTY Anupam Agarwal, MD Division of Nephrology University of Alabama at Birmingham Birmingham, AL USA Steven Alexander, MD Professor of Pediatrics Chief, Pediatric Nephrology Lucile Packard Children's Hospital at Stanford Stanford University Medical Center Stanford, CA USA Amelia Allsteadt, BSN, RN, CNN Nurse Manager Texas Childrens Hospital Houston, TX USA David Askenazi, MD, MSPH Children's of Alabama University of Alabama at Birmingham Division of Pediatric Nephrology Birmingham, AL USA Simon Atkinson, PhD Indiana University Purdue University Indianapolis Indianapolis, IN USA 5 Linda Awdishu, PharmD, MAS Associate Clinical Professor of Pharmacy and Medicine The Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD Asst. Clinical Professor, School of Pharmacy, UCSF San Diego, CA USA Sean Bagshaw, MD, MSc, FRCPC Division of Critical Care Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton, Al CANADA Ian Baldwin, RN, PhD, FACCCN Professor of Intensive Care Nursing Department of Intensive Care, Austin Hospital RMIT University Deakin University Melbourne, Vi AUSTRALIA Rajit Basu, MD MMI Center for Acute Care Nephrology Division of Critical Care Cincinnati Children's Hospital Medical Center Cincinnati, OH USA Josee Bouchard, MD Hopital du Sacre-Coeur de Montreal Universite de Montreal Montreal, Qu CANADA Emmanuel Burdmann, MD, PhD Associate Professor, Division of Nephrology University of Sao Paulo Medical School Sao Paulo, SP BRAZIL Vincenzo Cantaluppi, MD Associate Professor of Nephrology University of Eastern Piedmont Maggiore della Carita University Hospital Novara, NO ITALY

7 AKI&CRRT 2016 FACULTY Jorge Cerda, MD, FACP, FASN Clinical Professor of Medicine Albany Medical College Capital District Renal Physicians Albany, NY USA Rajasekara Chakravarthi, MD, DNB (Nephrology) Director Nephrology Services Care Hospitals Institute of Medical Sciences Hyderabad, AP INDIA Lakhmir Chawla, MD Associate Professor of Medicine George Washington University Medical Center Washington, DC USA Rolando Claure-Del Granado, MD, FASN Professor of Medicine School of Medicine Universidad Mayor de San Simon Cochabamba, Co BOLIVIA Michael Connor, MD Assistant Professor Critical Care Medicine & Nephrology Division of Pulmonary, Allergy, Critical Care, & Sleep Medicine Emory University Atlanta, GA USA Dinna Cruz, MD, MPH Division of Nephrology-Hypertension University of California San Diego San Diego, CA USA Andrew Davenport, MD, FRCP Consultant Nephrologist Honorary Reader Royal Free Hospital University College London Medical School London, ENGLAND Judy Davidson, DNP, RN, FCCM, FAAN EBP/Research Nurse Liaison UC San Diego Health San Diego, CA USA Prasad Devarajan, MD, FAAP Director of Nephrology and Hypertension Cincinnati Children's Hospital Medical Center University of Cincinnati College of Medicine Cincinnati, OH USA Xiaoquiang Ding, Prof Medical College Fudan University Shanghai, CHINA Kent Doi, MD Department of Emergency and Critical Care Medicine The University of Tokyo Tokyo, TK JAPAN Zheng Dong, PhD Medical College of Georgia and Charlie Norwood VAMC Augusta, GA USA Geoffrey Fleming, MD Vanderbilt University Medical Center Department of Pediatrics Division of Critical Care Nashville, TN USA Noel Gibney, MB FRCP(C) Professor Division of Critical Care Medicine Faculty of Medicine and Dentistry, University of Alberta Edmonton, AB CANADA Stuart Goldstein, MD Professor of Pediatrics, University of Cincinnati College of Medicine Division of Nephrology and Hypertension & The Heart Institute Director, Center for Acute Care Nephrology Cincinnati Children's Hospital Medical Center Cincinnati, OH USA Patty Graham, RN, MS, CCRN, CS UCSD Medical Center San Diego, Ca USA Raymond Harris, MD Division of Nephrology and Hypertension Department of Medicine Vanderbilt University Medical Center Nashville, TN USA Patrick Honore, MD, PhD Professor of Medicine & Head of Clinics Intensive Care Department UZ Brussel VUB University Brussels Jette, Br BELGIUM Eric Hoste, MD, PhD Department of Intensive Care Medicine Ghent University Hospital Gent, Oo BELGIUM Michael Joannidis, Prof. MD Division of Intensive Care and Emergency Medicine Department of Internal Medicine Medical University Innsbruck Innsbruck, AUSTRIA Luis Juncos, MD Division of Nephrology University of Mississippi Medical Center Jackson, MS USA Patrick Kamath, MD Professor of Medicine Mayo Clinic, College of Medicine Rochester, MN USA Kianoush Kashani, MD Mayo Clinic Rochester, MN USA John Kellum, MD Professor, Critical Care Medicine University of Pittsburgh School of Medicine Pittsburgh, PA USA Gilbert Kinsey, PharmD, PhD University of Virginia Department of Medicine - Division of Nephrology Center for Immunity, Inflammation and Regenerative Medicine Crozet, VA USA Jay Koyner, MD University of Chicago Chicago, IL USA Chris Laing, Dr Royal Free London NHS Foundation Trust University College London London AKI Network London, Gr UK 6

8 AKI&CRRT 2016 FACULTY David Leaf, MD, MMSc, FASN Division of Renal Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA USA Andrew Lewington, MD Renal Association Leeds, YK UNITED KINGDOM Etienne Macedo, MD, PhD University of Sao Paulo Sao Paolo, SP BRAZIL Alan Maisel, MD Professor of Medicine University of California, San Diego San Diego, CA USA Isagani Marquez, BSN, RN University of California San Diego Medical Center San Diego, CA USA Peter McCullough, MD, MPH Baylor University Medical Center Dallas, TX USA Ravindra Mehta, MBBS, MD, DM, FACP Professor of Clinical Medicine University of California, San Diego School of Medicine Associate Chair for Clinical Research, Department of Medicine Director, Clinical Nephrology and Dialysis Programs UCSD Medical Center San Diego, CA USA Theresa Mottes, BSN, RN, CDN Research Nurse Center for Acute Care Nephrology Cincinnati Children's Hospital Medical Center Cincinnati, OH USA Bruce Mueller, PharmD Associate Dean for Academic Affairs and Professor Dept. of Clinical Pharmacy, College of Pharmacy Associate Director, Department of Pharmacy Services, University Hospital University of Michigan Ann Arbor, MI USA Patrick Murray, MD Dean, School of Medicine & Medical Science University College Dublin Consultant in Nephrology & Clinical Pharmacology Mater Misericordiae University Hospital Dublin, D IRELAND Mitra Nadim, MD University of Southern California Los Angeles, CA USA Eisei Noiri, MD., PhD. The University of Tokyo Hospital Tokyo, JAPAN Noel Oabel, BSN, RN, CNN Acute Nephrology Programs University of California San Diego Medical Center San Diego, CA USA Mark Okusa, MD Division of Nephrology University of Virginia Charlottesville, VA USA Marlies Ostermann, MD Guy's & St Thomas Hospital Department of Nephrology & Critical Care London, Gr UNITED KINGDOM 7 Paul Palevsky, MD VA Pittsburgh Healthcare System University of Pittsburgh School of Medicine Sewickley, PA USA Peter Pickkers, MD, PhD Department of Intensive Care Medicine Radboud University Medical Centre Nijmegen, Netherlands John Prowle, MA MSc MD FRCP FFICM Senior Lecturer in Intensive Care Medicine Barts and the London School of Medicine and Dentistry Queen Mary, University of London London, UK W. Brian Reeves, MD Division of Nephrology Penn State College of Medicine Hershey, PA USA Claudio Ronco, MD Director, Department of Nephrology International Renal Research Institute Vicenza St. Bortolo Hospital Vicenza, ITALY Mitchell Rosner, MD Division of Nephrology University of Virginia Charlottesville, VA USA Amber Sanchez, MD University of California San Diego Medical Center San Diego, CA USA Miet Schetz, MD, PhD Associate Professor of Medicine Department of Intensive Care University Hospital KULeuven Leuven, BELGIUM Nick Selby, MD Centre for Kidney Research and Innovation Division of Medical Sciences and Graduate Entry Medicine University of Nottingham Derby, UK Andrew Shaw, MB, FRCA, FFICM, FCC Professor and Executive Vice Chair Department of Anesthesiology VUMC Nashville, TN USA Teri Shell, RN University Of Alabama Birmingham, Al USA Scott Sutherland, MD Lucile Packard Children's Hospital Stanford University Medical Center Stanford, CA USA Jordan Symons, MD Division of Pediatric Nephrology Seattle Children's Hospital Seattle, WA USA Joshua Thurman, MD University of Colorado Anschutz Medical Campus Aurora, CO USA Ashita Tolwani, MD Professor, Division of Nephrology University of Alabama at Birmingham Birmingham, AL USA

9 AKI&CRRT 2016 FACULTY James Tumlin, MD University of Tennessee College of Medicine Chattanooga, TN USA Volker Vallon, MD Departments of Medicine and Pharmacology Division of Nephrology & Hypertension UC San Diego and VASDHCS San Diego, CA USA Manjeri Venkatachalam, MBBS Department of Pathology University of Texas Health Science Center San Antonio, TX USA Jean-Louis Vincent, MD PhD Consultant Department of Intensive Care Erasme Hospital Universite Libre de Bruxelles Brussels, NA BELGIUM Francis Perry Wilson, MD, MSCE Yale University School of Medicine Department of Medicine New Haven, CT USA Paul Wischmeyer, MD Department of Anesthesiology and Pediatrics Denver, CO USA Motoko Yanagita, MD, PhD Department of Nephrology Kyoto University Graduate School of Medicine Kyoto, Ky JAPAN Li Yang, MD Renal Division Peking University First Hospital Beijing, CHINA Karen Yeates, MD Glenburnie, On CANADA David Ward, MD, FRCP University of California San Diego San Diego, CA USA David Warnock, MD University of Alabama at Birmingham Birmingham, AL USA 8

10 ACKNOWLEDGEMENTS AKI&CRRT 2016 ACKNOWLEDGEMENTS of EDUCATIONAL GRANTS AND CORPORATE CONTRIBUTIONS We would like to offer a very special thank you to the following companies for their educational grant support as of February 5, 2016 FINANCIAL SUPPORT AM Pharma B.V. Astute Medical, Inc. Baxter Healthcare Corporation Fresenius Medical Care Renal Therapies Group, LLC Grifols USA, LLC Pfizer Relypsa, Inc. sphingotec, LLC ZS Pharma FELLOWS IN TRAINING SUPPORT Baxter Healthcare Corporation ACKNOWLEDGEMENT of EXHIBITORS Would like to acknowledge the following companies and organizations for exhibiting at this conference: Baxter Healthcare Corporation Alexion Pharmaceuticals, Inc. Astute Medical, Inc. NxStage Medical, Inc. B. Braun Medical, Inc. Mallinckrodt Pharmaceuticals Bard Access Systems Clinical Nephrology Fresenius Medical Care - Inpatient Services International Society of Nephrology Karger Publishers Nikkiso America, Inc. 9

11 ELECTIVE WORKSHOPS AKI&CRRT 2016 PROGRAM/INDEX TUESDAY, FEBRUARY 16 PW1 PRE-CONFERENCE AKI SYMPOSIUM 7:55am-5:30pm Changing Paradigms in Acute Kidney Injury: From Mechanisms to Management Presented by UAB/UCSD O Brien Center for AKI Research 7:55 am Opening Remarks - Ravindra Mehta, MD PLENARY 1 Molecules, Mechanisms and Targets Co-Chairs: Anupam Agarwal, MD and Zheng Dong, MD 8:00-8:20 TRPM2 Channels, Oxidant Stress and Ischemic AKI - W. Brian Reeves :20-8:40 Telomerase, Autophagy and Acute Kidney Injury - Raymond Harris 8:40-9:00 Tubular Transport in Acute Kidney Injury - Volker Vallon 9:00-9:20 Iron and Acute Kidney Injury - David Leaf 9:20-9:40 Sphingolipid Signaling and Kidney Disease Fibrosis: New Therapeutic Target Mark Okusa :40-10:00 Discussion 10:00-10:15 Coffee Break PLENARY 2 Of Mice and Men: Harmonizing Human and Animal AKI Co-Chairs: Raymond Harris MD and Mark Okusa, MD 10:15-10:35 Organ Cross Talk: Kidney Heart Interactions - Kent Doi :35-10:55 Macrophage Dynamics in AKI - Gilbert Kinsey :55-11:15 Models of AKI Leading to CKD - Manjeri Venkatachalam :15-11:35 micrornas in the Pathogenesis and Diagnosis of AKI - Zheng Dong 11:35-11:55 Insights Into the Mechanisms of the AKI to CKD Continuum - Motoko Yanagita :55-12:15 Discussion 12:15-1:15 pm Lunch Hosted by Conference PLENARY 3 Bench to Bedside: Translating Discoveries to Clinical Care Co-Chairs: Jean Louis Vincent, MD and Claudio Ronco, MD 1:15-1:35 sirna and Gene Delivery Approaches for Treating AKI - Simon Atkinson 1:35-1:55 Role of Complement in Acute Kidney Injury - Joshua Thurman :55-2:15 Lipoic Acid in the Prevention of AKI - Peter McCullough 2:15-2:35 Remote Ischemic Preconditioning: Bench to Bedside and Back - John Kellum :35-2:55 Mineralocorticoid Receptor Antagonism in AKI: A New Hope? - Luis Juncos 2:55-3:15 Discussion 3:15-3:30 Coffee Break PLENARY 4 Controversies in AKI Co-Chairs: Paul Palevsky MD and Patrick Murray, MD 3:30-3:50 Frequency Bias: A New Limitation of Creatinine as an AKI Biomarker Francis Perry Wilson 3:50-4:10 Community vs Hospital Acquired AKI: Do We Have the Metrics? David G. Warnock 4:10-4:30 Oliguria and Biomarker for AKI? How Are They Confounded? Michael Joannidis 4:30-4:50 Renal Stress Testing in AKI - Lakhmir Chawla 4:50-5:10 The Puzzle of Subclinical AKI - Claudio Ronco 5:10-5:30 Care Bundles in AKI Do They Work? - Nicholas Selby 5:30 Adjourn - Reception, Poster Review and Oral Poster Sessions 10

12 ELECTIVE WORKSHOPS AKI&CRRT 2016 PROGRAM/INDEX TUESDAY, FEBRUARY 16 PRE-CONFERENCE ELECTIVE WORKSHOP 7:45am-5:30pm PW2 Practice Based Learning in CRRT The Science and the Art A separate hand-out with schedule and information will be distributed to workshop attendees 7:45-8:00am Opening Remarks - (Tolwani, Cerda) :00-8:45 Pre-test - (Tolwani, Cerda) :45-9:25 AKI and Patient Selection for CRRT - (Cerda) :25-10:10 CRRT: The Technical Questions - Modality, A/C, Solutions, Dose - (Tolwani) :10-10:25 Coffee Break 10:25-11:05 CRRT: The Technical Questions - Access, Membrane, Circuit - (Juncos) 11:05-11:35 CRRT Outcome Studies: Survival and Renal Recovery - (Connor) 11:35-12:00 Developing, Implementing, Maintaining and Financial Aspects of CRRT - (Cerda) :00-1:15pm Lunch Hosted by Conference for Workshop Participants 1:15-3:30 Hands-On Workshop Rotations - All Teams The hands-on sessions will use a case-based approach to provide training on different aspects of CRRT. All participants will be allocated to teams of 6 to 8 that will have nurses, pharmacists and physicians represented in each team. Each team will go through four interactive case discussions and role-playing with team members. The workshop is divided into four (4) sessions 45 minutes in length that will occur simultaneously. Each session will be repeated 4 times so teams can rotate through each session in order to maximize the learning opportunity. Teams rotate during 5 minute breaks between sessions. Pediatric teams will rotate only through the pediatric section. SESSION 1 CRRT Prescription/Order Sets/Documentation - (Cruz, Cerda, Graham)...44 Operationalizing the prescription for different modalities; documentation SESSION 2 Circuit, Anticoagulation, Citrate Protocols - (Tolwani, Awdishu, Shell)...45 Access and circuit setup, citrate anticoagulation, monitoring and adjustments SESSION 3 CRRT Dose/Fluid/Drug Dosing - (Connor, Mueller, Oabel) Setting the machine for volume management, solute clearances and adjustments for drugs and nutritional support SESSION 4 Monitoring, Alarms and Connections with Other Therapies (Baldwin, Juncos, Marquez)...46 Assessment and correction of alarm states and managing connections with ECMO/ECCOR and apheresis PEDIATRIC SESSION - (Askenazi, Goldstein, Mottes)...48 Modality selection, circuit modifications, therapy dosing, monitoring, adjustments for targeted interventions 3:30-3:45 Coffee Break 3:45-4:45 Interactive Clinical Case (Decision Making) - (Tolwani, Connor) 4:45-5:30 Post-test and Wrap-up - (Tolwani, Cerda) 5:30 Adjourn 11

13 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX WEDNESDAY AFTERNOON, FEBRUARY 17 SESSION I: PATIENT CHARACTERISTICS 1:10pm-3:30pm Plenary 1 MINI-SYMPOSIA Organ Dysfunction in the Critically Ill Patient: Emerging Concepts Co-chairs: Michael Joannidis, MD, Miet Schetz, MD 1:10-1:15 Opening Remarks Ravindra L. Mehta, MD 1:15-1:30 What Really Happens in the Operating Room During Cardiac Surgery? Andrew D. Shaw, MB 1:30-1:45 Fluid Balance in Septic Patients John Louis Vincent, MD 1:45-2:00 Volume Bolus with Balanced Crystalloids in ICU Patients? Eric AJ Hoste, MD 2:00-2:15 Pneumonia and AKI: Much Worse Together Lakhmir S. Chawla, MD 2:15-2:30 Etiology and Prediction of AKI After Major Trauma...62 John Prowle, MD 2:30-2:45 Immunoparalysis in Sepsis: Can We Correct? Peter Pickkers, MD 2:45-3:10 SPECIAL LECTURE Role of Microbiome in Critical Illness: Diagnostic and Treatment Options for the Future Paul Wischmeyer, MD 3:10-3:30 Panel Discussion 3:30-4:00 Coffee Break 12

14 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX WEDNESDAY AFTERNOON, FEBRUARY 17 Continuation of: SESSION I: PATIENT CHARACTERISTICS 4:00pm-6:00pm Plenary 2 MINI-SYMPOSIA Acute Kidney Injury (AKI): Pathophysiology Co-Chairs: Peter A. McCullough, MD, Mitchell H. Rosner, MD 4:00-4:15 Endothelial Barrier Function is Critical for Renal Recovery...63 Mark D. Okusa, MD 4:15-4:30 Lung Transplantation and AKI...64 Sean Bagshaw, MD, MSc, FRCPC 4:30-4:45 Sepsis-associated AKI Has Unique Epidemiology and Molecular Signatures...65 John A. Kellum, MD 4:45-5:00 Cardiac Surgery Associated AKI...66 Xiaoquiang Ding, Prof 5:00-5:15 NINJAs Are Able to Reduce Nephrotoxic AKI Stuart L. Goldstein, MD 5:15-6:00 My Favorite Idea in AKI and RRT Moderator: Noel Gibney, MB John A. Kellum, MD Claudio Ronco, MD John Louis Vincent, MD 6:00-8:00 EXHIBIT RECEPTION, POSTERS & ORAL PRESENTATIONS 13

15 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX THURSDAY MORNING, FEBRUARY 18 SESSION II: CONTROVERSIES IN CRITICAL CARE NEPHROLOGY 10:00am-12:15pm Plenary 3 MINI-SYMPOSIA Challenges in ICU Management Co-Chairs: Josee Bouchard, MD, Bruce A. Mueller, PharmD 10:00-10:15 Nutritional Support in AKI: Do We Know What to Do? Paul Wischmeyer, MD 10:15-10:30 Does Anything Work to Protect the Kidneys? John Louis Vincent, MD 10:30-10:45 Diagnostic and Therapeutic Potential of Microevsicles in AKI...75 Vincenzo Cantaluppi, MD 10:45-11:00 Recovery: The New Target for AKI Results of ADQI XVI John A. Kellum, MD 11:00-11:15 Renal Dysfunction as a Prognostic Marker in Liver Disease Patrick Kamath, MD 11:15-11:30 Kidney Injury in Heart Failure - Results of the AKINESIS Study Patrick T. Murray, MD 11:30-12:00 SPECIAL LECTURE - Jeff Gray Memorial Award Oration Translating AKI Biomarkers Prasad Devarajan, MD 12:00-12:15 Award Presentation 12:15-1:45 Conference Luncheons 14

16 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX THURSDAY AFTERNOON, FEBRUARY 18 SESSION III: EMERGING CONCEPTS IN AKI AND RRT 1:45pm-3:30pm Plenary 4 MINI-SYMPOSIA Novel Strategies in AKI Management Co-Chairs: Andrew Lewington, MD, Li Yang, MD 1:45-2:00 How to Remove H2O and CO2 with an Extracorporeal Circuit Claudio Ronco, MD 2:00-2:15 Making Iodinated Contrast Less Nephrotoxic with Cyclodextrin Peter A. McCullough, MD 2:15-2:30 Diagnostic Assessment of AKI in the ICU Patrick T. Murray, MD 2:30-2:45 Hemodynamic Optimization of AKI Stage 1 Marlies Ostermann, MD 2:45-3:00 Beware of Diuretics John Louis Vincent, MD 3:00-3:15 Pharmacologic, Extracorporeal Renal and/or Hepatic Support for HRS-1 Mitra Nadim, MD 3:15-3:30 AKI and CPR is Hypothermia Useful? Michael Joannidis, MD 3:30-4:00 Coffee Break 15

17 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX THURSDAY AFTERNOON, FEBRUARY 18 Continuation of: SESSION III: EMERGING CONCEPTS IN AKI AND CRITICAL CARE 4:00pm-6:00pm Plenary 5 MINI-SYMPOSIA Challenges and Controversies in Renal Support and CRRT Co-chairs: Ian Baldwin, RN, Ashita Tolwani, MD 4:00-4:15 Bicarbonate Solutions in CRRT: Help or Harm? Kianoush Kashani, MD 4:15-4:30 Facilitating Recovery from AKI Requiring RRT Dinna Cruz, MD 4:30-4:45 Optimizing Fluid Removal on RRT Ravindra L. Mehta, MD 4:45-5:00 Albumin Detoxification for Sepsis in CRRT? Patrick M. Honore, MD 5:00-5:15 Assessing Energy Expenditure in RRT Andrew Davenport, MD 5:15-5:45 DEBATE - Timing of RRT in AKI: Start Early or Not...83 Pro: Paul Palevsky, MD - Con: Miet Schetz, MD Moderator: Stuart L. Goldstein, MD 5:45-6:00 Top Abstract Awards 16

18 PLENARY SESSIONS AKI&CRRT 2016 PROGRAM/INDEX FRIDAY MORNING, FEBRUARY 19 SESSION IV: IMPROVING OUTCOMES IN AKI 8:00am-10:40am Plenary 6 MINI-SYMPOSIA Global Burden of AKI Co-Chairs: Emmanuel Burdmann, MD and Jorge Cerda, MD 8:00-8:30 Epidemiology of AKI in the ICU O'Brien AKI Registry - Josee Bouchard, MD AKI EPI Study - Eric AJ Hoste, MD 8:30-8:45 The Changing Face of AKI in China...84 Li Yang, MD 8:45-9:00 Drug Induced Nephrotoxicity: The DIRECT Study Linda Awdishu, PharmD 9:00-9:15 Renal Biopsy in AKI: Do We Know What We Are Treating? Rajasekara Chakravarthi, MD 9:15-9:30 AKI Networks to Improve Care: The UK Experience Chris Laing, MD 9:30-9:45 The ISN 0by25 AKI Global Snapshot: What Have We Learnt? Ravindra L. Mehta, MD 9:45-10:00 Risk Factors for AKI: Are They the Same Across the World? Etienne Macedo, MD 10:00-10:15 Status of RRT for AKI in Japan...85 Kent Doi, MD 10:15-10:40 SPECIAL LECTURE - Implementing an Educational and Protocol Management Strategy for Improving Outcomes in AKI in Low Resource Settings: The Moshi Experience Karen Yeates, MD 10:40-11:00 Coffee Break 17

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20 WORKSHOPS AKI&CRRT 2016 PROGRAM/INDEX WEDNESDAY MORNING, FEBRUARY 17 8:00am-9:30am SIMULTANEOUS STANDARD WORKSHOPS GROUP 1 A01 Using Kidney Biomarkers for AKI 1: Risk Assessment, Diagnosis and Staging (C,N,AP) 50 Rajit Basu, MD, Jay Koyner, MD, Patrick T. Murray, MD B02 Strategies for Optimizing the CRRT Circuit (Access, Anticoagulation and Monitoring) Citrate Anticoagulation (C,N,AP) 52, 54 David Askenazi, MD, Ian Baldwin, RN, PhD, Luis Juncos, MD C03 Using Electronic Medical Records and Big Data to Improve Care in AKI C,N,AP) Stuart L. Goldstein, MD, Nick Selby, MD, Francis P. Wilson, MD D04 Managing Patients with AKI and Liver Failure 1: Pathophysiology, Differential Diagnosis, Therapy, Use of RRT, Liver Support, Strategies for Bridge to Transplant (C,N,AP) Andrew Davenport, MD, Patrick Kamath, MD, Mitra Nadim, MD E05 Assessment of Fluid Responsiveness, Hemodynamic Monitoring and Targets (C, N) Michael Joannidis, MD, Kianoush Kashani, MD, Peter Pickkers, MD F06 Mobile Health Applications for AKI Management (C,N,AP) Emmanuel Burdmann, MD, Rajasekara Chakravarthi, MD Karen Yeates, MD G07 Principles of Plasma Exchange, Applications and Practical Issues (C,N,AP) Eisei Noiri, MD, Amber Sanchez, MD, David M. Ward, MD 9:30-10:00 Coffee Break 19

21 WORKSHOPS AKI&CRRT 2016 PROGRAM/INDEX WEDNESDAY MORNING, FEBRUARY 17 10:00am-11:30am SIMULTANEOUS STANDARD WORKSHOPS GROUP 2 A08 Using Kidney Biomarkers for AKI 2: Differential Diagnosis, Interventions and Prognosis (C,N,AP) 55 Josee Bouchard, MD, Kent Doi, MD, Stuart L. Goldstein, MD B09 CRRT for the Experienced User 1 (I,N,AP) 56, 57 Ian Baldwin, RN, PhD, Rolando Claure, MD, Claudio Ronco, MD C10 Starting and Stopping RRT for AKI: Principles and Practice (A) Etienne Macedo, MD, PhD, Ravindra L. Mehta, MD D11 Managing Patients with Sepsis 1 : Pathophysiology, Diagnosis, Assessment, Resuscitation, Drug Management, Techniques for Disease Modification, Organ Support and Renal Protection (C,N,AP) 58 Geoffrey Fleming, MD, Patrick M. Honoré, MD, John Louis Vincent, MD E12 Fluids and Solutions in AKI Management: Crystalloids, Colloids and Blood Products - When and How to Use (I,N,AP) Eric AJ Hoste, MD, John A. Kellum, MD, Andrew D. Shaw, MB F13 Not Your Parents' CRRT: Advanced Pediatric-Specific Techniques (I,N,AP) Theresa Mottes, RN, Scott Sutherland, MD, Jordan M. Symons, MD G14 Practical Issues in Plasmapheresis: Setup and Troubleshooting, Combined CRRT with Apheresis (C,N) Isagani Marquez, RN, Noel Oabel, RN, David M. Ward, MD 11:30-1:00 Luncheons Hosted by Conference 20

22 WORKSHOPS AKI&CRRT 2016 PROGRAM/INDEX THURSDAY MORNING, FEBRUARY 19 8:00am-9:30am SIMULTANEOUS STANDARD WORKSHOPS GROUP 3 9:30-10:00 Coffee Break A15 Optimal Care for AKI: The 5 R Approach (C,N,AP) 67 Jorge Cerda, MD, Andrew Lewington, MD, Karen Yeates, MD B16 CRRT for the Experienced User 2: Solutions, Fluid 69, 70 Removal Fluid Balance, Monitoring (A) Ravindra L. Mehta, MD, John Prowle, MD C17 Drug Induced Kidney Injury in the ICU: Mechanisms, Susceptibility, Diagnosis, Management Strategies (A,N) Bruce A. Mueller, PharmD, Scott Sutherland, MD D18 Managing Heart Failure and Cardio-Renal Syndrome: Pathophysiology, Diagnosis, Drug Management, Ultrafiltration, Renal Support and RRT for Patients with Ventricular Assist Devices and Artificial Hearts (A,N) Luis Juncos, MD, James A. Tumlin, MD E19 Nutrition Assessment and Management in AKI and CRRT (I,N) Michael Joannidis, MD, Marlies Ostermann, MD, Paul Wischmeyer, MD F20 Pediatric Dialysis Techniques 2: CRRT in the Newborn; ECMO, Combination Therapies, Drug Dosing, Transitions (C,N,AP) 73 Amelia Allsteadt, BSN, David Askenazi, MD, Geoffrey Fleming, MD G21 Sorbent Based and Hybrid Therapies for Extracorporeal Support (I,N,AP) Dinna Cruz, MD, Patrick M. Honore, MD, Eisei Noiri, MD 21

23 AKI&CRRT 2016 PROGRAM/INDEX MEET THE EXPERT SESSIONS (Electives, CME Available) WEDNESDAY MORNING, FEBRUARY 17 7:00-8:00 ME1 MEET THE EXPERTS (elective, CME Available) How I Assess Patients in the ICU and My Approach to Oliguria Peter Pickkers, MD, PhD & John Louis Vincent, MD, PhD 7:00-8:00 ME2 MEET THE EXPERTS (elective, CME Available) What Strategies Do I Use to Prevent AKI Peter A. McCullough, MD, MPH & Paul Palevsky, MD THURSDAY MORNING, FEBRUARY 19 7:00-8:00 ME3 MEET THE EXPERTS (elective, CME Available) How do I Manage Patients with Combined Liver and Kidney Dysfunction? Patrick Kamath, MD, Mitra Nadim, MD 7:00-8:00 ME4 MEET THE EXPERTS (elective, CME Available) How I Use the KDIGO AKI Guidelines to Manage Patients John A. Kellum, MD, Claudio Ronco, MD LUNCH SYMPOSIA WEDNESDAY, FEBRUARY 17 11:30-1:00 A. New Kids on the Block: Emerging Biomarkers in AKI, CKD and (CME Available) Cardiorenal Syndrome 60 Moderators: Stuart L. Goldstein, MD & Patrick T. Murray, MD Eric AJ Hoste, MD, Alan Maisel, MD, Marlies Ostermann, MD 11:30-1:00 B. Fluid Management of the Critically Ill Patient: Crystalloids, Colloids and (CME Available) Blood Products 61 Co-Chairs: Michael Connor, MD & Peter Pickkers, MD John Prowle, MD, Andrew D. Shaw, MB, John Louis Vincent, MD 11:30-1:00 C. Novel Approaches for Recognition and Management of Life Threatening (CME Available) Complications of AKI and CKD 12:15pm-1:45pm (CME Available) Co-Chairs: Chris Laing, MD & Jordan M. Symons, MD Peter A. McCullough, MD, Mitchell H. Rosner, MD, James A. Tumlin, MD THURSDAY, FEBRUARY 19 D. Injury Matters: The Role of Risk Assessment and Early Intervention in AKI 77 Co-Chairs: Lakhmir S. Chawla, MD & John A. Kellum, MD Rajit Basu, MD, Kianoush Kashani, MD, Jay Koyner, MD 12:15pm-1:45pm E. Improving Outcomes in AKI and CRRT: Does Quality Matter? 79, 81 (CME Available) Co-Chairs: Etienne Macedo, MD & Mitchell H. Rosner, MD Sean Bagshaw, MD, Ian Baldwin, RN, Theresa Mottes, BSN 12:15pm-1:45pm F. Winning The War Against Critical Illness: Role of Post-ICU Quality of Life 82 (CME Available) Co-Chairs: Steven R. Alexander, MD & Michael Joannidis, MD Judy E. Davidson, RN, Noel Gibney, MB, Paul Wischmeyer, MD 22

24 POSTER ABSTRACTS AKI&CRRT 2016 PROGRAM/INDEX CME CREDIT DOES NOT APPLY FOR POSTER SESSIONS Posters are listed with lead authors only, see abstract or actual posters for complete author list. Viewing of all posters and select Oral Presentations: Tues. 5:30-7:30pm & Wed. 6:00-8:00pm. POSTER ABSTRACT INDEX EPIDEMIOLOGY AND OUTCOMES FROM AKI Poster Number 1. Long Term Renal Outcomes in Critically Ill Patients with Acute Kidney Injury 87 Hui Zhuan Tan 2. A Systematic Review Of Health-Related Quality-Of-Life Among Critically Ill Survivors Of Acute Kidney Injury 88 Pierre-Marc Villeneuve 3. Epidemiology of AKI Requiring Dialysis in Critically Ill Children 89 Josee Bouchard 4. A Multicenter Population-based Epidemiological Study of Intensive Care Unit (ICU) Acquired Acute Kidney Injury (AKI) in a Brazilian Amazon Region 90 Fernando Melo 5. Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN): Incidence and Outcomes from an International Multi-center Cohort Study 91 Jennifer Jetton 6. Risk factors for Neonatal Acute Kidney Injury: Results from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study 92 Jennifer Jetton 7. Low Pre-operative Serum Bicarbonate Levels Predict Acute Kidney Injury after Cardiac Surgery 93 Seohyun Park 8. A clinical risk model to predict acute kidney injury after cardiac surgery in Chinese patients 94 Wuhua Jiang 9. Subclinical Acute Kidney Injury is an Early Stage of AKI 95 Rolando Claure-Del Granado 10. High Level of Plasma Pro-Enkephalin (penkid) in the General Population Predicts Deterioration of Kidney Function and Incidence of Chronic Kidney Disease 96 Joachim Struck 11. A Worldwide Multicentre Evaluation of Acute Kidney Injury in Septic and Non-septic Critically Ill Patients: The Intensive Care Over Nations (ICON) Audit 97 Esther Peters 12. Progression of Chronic Kidney Disease and Cardiovascular Outcomes After Cardiac Catheterization Associated-Acute Kidney Injury and Comparison with Population Controls 98 R. Solomon/ J.Brown 13. Plasma Pro-Enkephalin and Poor Long-Term Outcome in Renal Transplant Recipients 99 Joachim Struck 14. Hospital Re-admission and Post-discharge Mortality in Critically Ill patients with Acute Kidney Injury 100 Peishan Lee 15. The Association of Plasma Pro-Enkephalin with Renal Function Decline 101 Joachim Struck 16. Furosemide Stress Test, Renal Angina Index, and Urinary Sediment: Which I Should Use to Predict AKI? 102 Daniela Torrico-Guillen 23

25 POSTER ABSTRACTS AKI&CRRT 2016 PROGRAM/INDEX 17. The Role of Bioimpedance Analysis as a Predictor of Outcomes in Acute Kidney Injury Patients Requiring Renal Replacement Therapy 103 Sadudee Peerapornratana 18. Evolution of AKI Treatment in ICU in 2 Hospitals of Piedmont (Italy) in The Last 15 Years: Analysis of Outcome, Progression Toward CKD and RRT Modality 104 Marita Marengo 19. Acute Kidney Injury In Non Renal Solid Organ Transplantation: a rising clinical problem 105 Vincenzo Cantaluppi 20. The Effect of the Choice of Contrast Media on Renal Failure Events in Inpatient Cardiovascular Procedures 106 Peter Mallow 21. Change of Estimated Glomerular Filtration Rate to Assess the Extent of Renal Recovery after Cardiac Surgery Associated Acute Kidney Injury 107 Jiarui Xu 22. Effect of Body Mass Index on Acute Kidney Injury after Cardiac Surgery 108 Zhouping Zou 23. Early Diagnosis of Severe Sepsis and Acute Kidney Injury, Judgment of Rapid Transport to Critical Care Center: Better Prognostic Factor 108 Hisashi Imahase 24. Changes of Epidemiology and Influencing Factors of Acute Kidney Injury After Cardiac Surgery- A Five year Study from 2009 to Zhouping Zou 25. Positive Fluid Balance as a Predictor of ICU Free Days in Patients with Kidney Disease Requiring Dialysis 110 Sharad Patel 26. Clinical Significance Of Renal Biopsy In AKI 111 Santosh Hedau 27. Acute Kidney Injury Recovery and the Risk of Chronic Kidney Disease in Sepsis Survivors 112 Javier Neyra 28. Post-Operative Acute Kidney Injury After Major Non-Cardiac Surgery and its Association with Death in the Following Year 113 John Prowle 29. Trajectory of Serum Creatinine after Major Surgery and Relationship with Acute Kidney Injury 114 John Prowle 30. Effect of Renin Angiotensin Blockade on Renal Function at Short and Mid Term in Patients Undergoing Coronary Angiography 115 Emmanuel Villalobos 97. Risk factors for acute kidney injury and mortality after orthotopic liver transplantation 115 Chen XiaoHong RESEARCH IN AKI 31. Incidence and Risk Factors of Acute Kidney Injury Following Transcatheter Aortic Valve Replacement 117 Wisit Cheungpasitporn 32. Proteomics of AKI induced by Maleic Acid on renal tubule cells 118 Lin Hugo 33. Analysis of hypo and hyperphosphatemia in an ICU cohort 119 Marcus Broman 34. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN): Design of a Retrospective Cohort Study 121 Jennifer Jetton 35. Computerized Prediction of AKI Outperforms Plasma NGAL: a Retrospective Analysis 122 Marine Flechet 24

26 POSTER ABSTRACTS AKI&CRRT 2016 PROGRAM/INDEX 36. A Case of Successful Treatment via Continuous Renal Replacement Therapy in Patient with Acute Kidney Injury due to Liver Abscess 124 Joon Seok Oh 37. Use of Cell-Cycle Arrest Biomarkers for Prediction of AKI in Infants Following Cardiac Surgery 125 Katja Gist 38. Plasma Pro-Enkephalin (penkid) and Renal Impairment in Severe Sepsis and Septic Shock: Data from the ALBIOS Trial 126 Joachim Struck 39. Milrinone Clearance in Critically Ill Infants with Acute Kidney Injury Following Cardiac Surgery 127 Katja Gist 40. Alkaline Phosphatase Protects Against Renal Inflammation Through Dephosphorylation of Lipopolysaccharide and Adenosine Triphosphate 128 Esther Peters 41. "Codigo IRA" Proposing a Rapid Response Team for the Detection and Management of Acute Kidney Injury in a University Hospital in Mexico 129 Lilia Rizo Topete 42. Ineffective Diuresis as a Biomarker During Early Postoperative Period Predicts Cardiac Surgery Associated Acute Kidney Injury 130 Salvador Lopez-Giacoman 43. Endothelial Progenitor Cell-Derived Extracellular Vesicles Protect From Sepsis-Associated Acute Kidney Injury 132 Vincenzo Cantaluppi 44. Immunomodulation of Regional Citrate Anticoagulation in Acute Kidney Injury Requiring Renal Replacement Therapy: A Randomized Controlled Trial 133 Sadudee Peerapornratana 45. Low Normal Values of Circulating Immune Cells with Increased Proportion of Vo2 T-Cells are Associated with Acute Kidney Injury after Endovascular Thoraco-Abdominal Aortic Repair 133 Ivan Gocze 46. Biomarkers of Acute Kidney Injury and Outcome in Critically Ill Patients 135 Joachim Struck 47. Urinary TIMP2xIGFBP7 Detects Patients with Positive Urine Microscopy Findings 136 Moritz Schanz 48. Vitamin D Deficiency is Common in Severe Acute Kidney Injury 137 Marlies Ostermann 49. Serum Cystatin C Predicts Renal Recovery Earlier Than Serum Creatinine Among Hospitalized Patients With Acute Kidney Injury 138 Kamel Gharaibeh 50. AMPK is activated in mice after CLP and that it protects from AKI 139 Hernando Gomez 51. Clinical and Subclinical Acute Kidney Injury in An Experimental Model of Sepsis 140 Xiukai Chen 52. Urinary TIMP2xIGFBP7 for Risk Prediction of Cardiorenal Syndrome 140 Martin Kimmel 53. Intraoperative CRRT Could be Useful During Liver Transplantation in Critically Ill patients with Renal Dysfunction 141 Seung Don Baek 54. Early CRRT Could be Defined as the Initiation of CRRT within 24 hours after vasopressor infusion 142 Baek Seung Don 55. Clinical Factors to Discriminate the AKI Patients Requiring CRRT over 6 days 144 Seung Don Baek 56. IGFBP7 and TIMP2 Expression and Secretion in Human Kidney Tubule Epithelial Cells 145 David R. Emlet 25

27 POSTER ABSTRACTS AKI&CRRT 2016 PROGRAM/INDEX 57. Mitochondrial Pathology And Glycolytic Shift During Proximal Tubule Atrophy After Ischemic AKI 146 Hui Geng 58. Renal Angiogenesis and Inflammatory Mediator Patterns Differ in Murine Models of Sepsis and VILI 147 Hepokoski Mark 59. The Prognostic Value of the Furosemide Stress Test in Predicting Delayed Graft Function Following Kidney Transplantation 148 Blaithin McMahon RRT TECHNIQUE CHARACTERISTICS 60. Cost Analysis Of Standardizing CRRT Processes 150 Salma Elbeharry 61. The comparison of double lumen temporary hemodialysis catheter and tunneled cuffed hemodialysis catheter on vascular access of continuous renal replacement therapy 151 Dongyeol Lee 62. Using a Bridging Technique for Continuous Renal Replacement Therapy Circuit Change Reduces Time off Therapy and Exposure to Blood Products 151 Rebecca Greene 63. Underutilization of Citrate Anticoagulation for Continuous Renal Replacement Therapy: A Survey Study 152 Sanders Lindsay 64. CRRT Without Anticoagulation. Feasibility and Prescription Factors 153 Armando Vazquez-Rangel RRT APPLICATIONS AND TARGETED INTERVENTION 65. Influence of Daily Fluid Balance prior to Continuous Renal Replacement Therapy on Outcomes in Critically Ill Patients 155 Jung-ho Shin 66. Use of Segmental Bioimpedance Analysis in Critically Ill Patients requiring Continuous Renal Replacement Therapy 156 Shin Jung-ho 67. Unusual and no renal indications for continuos renal replacement therapy (CRRT) 157 Jesus Mier Naylor 68. Extracorporeal Ultrafiltration Therapy for Acute Decompensated Heart Failure 159 Negiin Pourafshar 69. The Assessment of Volume Status by Bioelectrical Impedance Analysis and Lung Ultrasound in Septic AKI Patients Undergoing CRRT 159 Kee Youn Kyung 70. Development of Ciprofloxacin Dosing Recommendations for Critically Ill Patients Receiving SHIFT Renal Replacement Therapy 160 Alex Shaw 71. Monte Carlo Simulations (MCS) to Determine Optimal Levofloxacin Dosing for Gram Negative Infections in Patients Receiving SHIFT RRT 161 Weerachai Chaijamorn 72. Monte Carlo Simulations (MCS) to Determine Optimal Levofloxacin Regimens for Streptococcus pneumoniae Infections in Patients Receiving SHIFT Renal Replacement Therapy 163 Weerachai Chaijamorn 73. Slow Continuous Ultrafiltration Efficiently Improves Congestion in Acute Heart Failure without Adverse Impact on Renal Function: a Meta-analysis 164 Ankur Jain 26

28 POSTER ABSTRACTS AKI&CRRT 2016 PROGRAM/INDEX NEW TECHNOLOGY 74. Outside-In Hemofiltration For Prolonged Operation Without Clogging - Hydrodynamics, Filter Designs and Challenges 166 Mohamed Labib 75. Extracorporeal Carbon Dioxide (CO2) Removal with Continuous Renal Replacement Therapy - A Novel Therapy 167 Sachin Gupta 76. Experiences of blood purification using cytokine- adsorbing hemofilter (AN69ST) in pediatric population in Japan 168 Masaaki Nunomura 77. oxiris - a novel continuous renal replacement therapy and cytokine & endotoxin adsorption in septic patients - an Indian clinical experience 169 Sachin Gupta 78. In vitro and preliminary in vivo evalutation of new CRRT machine: KIBOUTM 170 Mauro Neri 79. Confirmation of Hemodialysis Central Venous Catheter Placement Using an Ultrasonographic Bubble Test 172 Passos Rogerio 80. Development and validation of an Acute Kidney Injury prediction model in Intensive Care Unit 173 Kianoush Kashani 81. Better "dose" for CRRT? Deliver the prescribed 174 Francesco Garzotto RRT RESEARCH 82. Adverse Effects of Hypophosphatemia during Renal Replacement Therapy for Acute Kidney Injury 175 Cynthia Ciwea Lim 83. Pharmacokinetics of Imipenem/Cilastatin in Critically Ill Burn Patients Undergoing High Volume Hemofiltation (HVHF) 176 Joanna Hudson 84. Continuous renal replacement therapy in the NICU; ten years experience in a single center 177 Mariko Sawada 85. Early versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury (The ELAIN-Trial): A randomized clinical trial 178 Alexander Zarbock 86. Effect of the intensity of Continuous renal Replacement Therapy in Patients With cardiac surgery associated Acute Kidney Injury (CRITERIA STUDY) 179 Huaban Liang 87. Relationship of Total Parenteral Nutrition Administration and Renal Replacement Therapy in the Intensive Care Unit 180 Jose Zaragoza 88. Impact of intensity of continuous renal replacement therapy on septic acute kidney injury 182 Kengo Mayumi 89. Predictive models of flow-induced hemolysis in pediatric CVC 182 Marta Zaccaria 90. Quality Indicators in Continuous Renal Replacement Therapy (CRRT) care in Critically Ill Patients: A Systematic Review 184 Rewa Oleksa 91. Probability of Target Attainment for Gentamicin Dosing in Modeled Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapies 185 Jerry Li 92. Coagulopathy Reduces Dialyzer Clotting in CRRT 186 Song ShinHan 27

29 AKI&CRRT 2015 PROGRAM/INDEX 93. Risk factors associated with Mortality in patients using Nafamostat mesilate as an Anticoagulant during CRRT 187 Eugene Kwon 94. Pressure and Hemolysis in Pediatric CVCs with Different Peristaltic Pumps 187 Marta Zaccaria NURSING ISSUES 95. Combined Continuous Renal Replacement Therapy(CRRT) and Therapeutic Plasma Exchange(TPE): An Alternative Methods in Dual Therapies 189 Isagani Marquez 96. Independently Implementing Slow Low Efficiency Dialysis in a Critical Care Unit 190 Bitton Marina 28

30 AKI & CRRT 2016 PW1 TRPM2 Channels, Oxidant Stress and Ischemic AKI Tuesday, February 16, 8:00-8:20 W. Brian Reeves MD Educational Objectives: 1. Recognize the role of a non-selective ion channel, TRPM2, in kidney ischemia-reperfusion injury. 2. Discuss potential interactions between Rac1 and TRPM2 in producing oxidant stress. Content Description: Dysregulation of cellular ionic homeostasis contributes to cell injury during ischemia. An early hallmark of ischemia is a loss of intracellular potassium and increases in intracellular sodium, chloride and calcium. Activation of ion channels is thought to contribute to this loss of ion homeostasis. However, the identity of these channels and the mechanisms whereby ion channels lead to kidney injury are not known. TRPM2, a member of the transient receptor potential-melastatin subfamily, is activated by oxidant stress, ADP-ribose, TNF and intracellular calcium, all of which are increased during kidney ischemia. We explored the possible role of TRPM2 in kidney ischemia-reperfusion injury. TRPM2 deficient mice were resistant to ischemic injury as reflected by improved kidney function, reduced histologic damage, suppression of pro-apoptotic pathways and reduced inflammation. Pharmacologic inhibition of TRPM2 was also protective. TRPM2 was localized mainly in kidney proximal tubule epithelial cells and studies in chimeric mice indicated that the effects of TRPM2 are due to expression in parenchymal cells rather than hematopoietic cells. TRPM2 deficient mice had less oxidative stress and lower levels of NADPH oxidase activity after ischemia. Rac1 is a component of the NADPH oxidase complex but its relation to TRPM2 and kidney ischemic injury is unknown. We found TRPM2-dependent activation of Rac1 after kidney ischemia. Active Rac1 and TRPM2 physically interact and active Rac1 increases expression of TRPM2 at the cell membrane. Finally, inhibition of Rac1 reduces oxidant stress and ischemic injury in vivo. These results demonstrate that TRPM2 increases oxidant stress through activation of Rac1. Therapeutic approaches targeting TRPM2 and/or Rac1 may be effective in reducing ischemic kidney injury. Suggested Reading: 1. Gao G, Wang W, Tadagavadi RK, Briley NE, Love MI, Miller BA, and Reeves WB. TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1. J Clin Invest. 2014;124(11): Linkermann A, Chen G, Dong G, Kunzendorf U, Krautwald S, and Dong Z. Regulated Cell Death in AKI. J Am Soc Nephrol. 2014;25(12): Sedeek M, Nasrallah R, Touyz RM, and Hébert RL. NADPH Oxidases, Reactive Oxygen Species, and the Kidney: Friend and Foe. J Am Soc Nephrol. 2013;24(10): Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, and Penner R. TRPM2 Functions as a Lysosomal Ca2+-Release Channel in β Cells. Science signaling. 2009;2(71):ra23-ra. 5. Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, and Qiao L. TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nature communications. 2013;4(

31 AKI & CRRT 2016 PW1 Sphingolipid Signaling and Kidney Disease Fibrosis: New Therapeutic Target Tuesday, February 16, 9:20-9:40 Mark D. Okusa MD Educational Objectives: 1. Describe pathogenesis of kidney fibrosis 2. Describe the sphingolipid signaling pathway 3. Describe the role of sphingolipid signaling pathway as a target to attenuate kidney fibrosis Content Description: Sphingosine 1-phosphate (S1P), a pleiotropic lysophospholipid that is involved in diverse functions such as cell growth and survival, lymphocyte trafficking, and vascular stability, is the product of sphingosine phosphorylation by two sphingosine kinase isoforms (SphK1 and SphK2). SphK1 and SphK2 have different subcellular localizations and may serve different functions. Localization of SphK1 near the plasma membrane provides S1P that is exported out of the cell (inside-out signaling)3 through ABC transporters and spinster homolog 2 (SPNS2), where it can bind to its five different G-protein coupled receptors (S1P1-5). SphK1 promotes cell survival and proliferation and regulates cell transformation. Less is known about SphK2, although several reports suggest that SphK2 serves proapoptotic functions. This presentation discussed the role of the sphingolipid pathway in acute kidney injury, repair and fibrosis. S1P1, S1P3 and SphK2 serve as new therapeutic targets for AKI and progressive kidney disease. Suggested Reading: Olivera A, Kohama T, Edsall L, et al. Sphingosine kinase expression increases intracellular sphingosine- 1-phosphate and promotes cell growth and survival. J Cell Biol 1999;147: Igarashi N, Okada T, Hayashi S, Fujita T, Jahangeer S, Nakamura S. Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. The Journal of biological chemistry 2003;278: Takabe K, Paugh SW, Milstien S, Spiegel S. "Inside-out" signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacological reviews 2008;60: Nishi T, Kobayashi N, Hisano Y, Kawahara A, Yamaguchi A. Molecular and physiological functions of sphingosine 1-phosphate transporters. Biochim Biophys Acta 2014;1841: Spiegel S, Milstien S. Functions of a new family of sphingosine-1-phosphate receptors. Biochim Biophys Acta 2000;1484: Maceyka M, Sankala H, Hait NC, et al. SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. The Journal of biological chemistry 2005;280: Bajwa A, Rosin DL, Chroscicki P, et al. Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury. J Am Soc Nephrol Bajwa A, Jo SK, Ye H, et al. Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury. J Am Soc Nephrol 2010;21: Jo SK, Bajwa A, Ye H, et al. Divergent roles of sphingosine kinases in kidney ischemia-reperfusion injury. Kidney Int 2009;75:

32 PW1 Organ Cross Talk: Kidney Heart Interactions Tuesday, February 16, 10:15-10:35 Kent Doi MD AKI & CRRT 2016 Educational Objectives: 1. Describe potential pathophysiological mechanisms of the organ cross talk between the kidney and the heart. 2. Discuss the role of mitochondria injury in the organ cross talk between the kidney and the heart. Content Description: Acute kidney injury (AKI) is a common complication in critically ill patients and subsequently worsens outcomes. In spite of remarkable advances in renal replacement therapy (RRT) techniques that enable management of AKI in hemodynamically unstable patients with shock, RRT-requiring severe AKI is still associated with an unacceptably high mortality rate. This suggests that targeting only kidney damage and loss of renal function has not been sufficient to improve outcomes of AKI patients. Recent basic research elucidated complex organ interactions in AKI between kidney and distant organs including heart. We recently reported that mitochondrial fragmentation by fission machinery might play a crucial role in cardiac dysfunction induced by AKI. Renal ischemia/reperfusion (IR) injury induced fragmentation of mitochondria in a fission-dominant manner with Drp1 activation and subsequent cardiomyocyte apoptosis in the heart. A Drp1 inhibitor, mdivi-1, administered before IR decreased mitochondrial fragmentation and cardiomyocyte apoptosis, and improved cardiac dysfunction induced by renal IR. Suggested Reading: 1. Sumida M, Doi K, Ogasawara E, Yamashita T, Hamasaki Y, Kariya T, Takimoto E, Yahagi N, Nangaku M, Noiri E. Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal Syndrome. J Am Soc Nephrol. 2015;26: : Kelly KJ. Distant effects of experimental renal ischemia/reperfusion injury. J Am Soc Nephrol. 2003;14: : Zhan M, Brooks C, Liu F, Sun L, Dong Z. Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int. 2013;83:

33 PW1 Macrophage Dynamics in AKI Tuesday, February 16, 10:35-10:55 Gilbert Kinsey PharmD, PhD AKI & CRRT 2016 Educational Objectives: 1. Describe the pre-clinical models used to investigate the mechanistic role of macrophages in AKI. 2. Discuss different approaches used to deplete macrophages. 3. Describe the role of macrophages in acute injury, repair, regeneration and fibrosis associated with AKI. Content Description: During AKI there is a rapid accumulation of macrophages, derived from circulating monocytes, in response to the release of pro-inflammatory mediators from the injured kidney. Both injurious and protective roles for macrophages have been reported, depending on the time frame of injury that is studied and the phenotype of the macrophages in the kidney. For example, depletion of macrophages prior to ischemic kidney injury or blocking the early influx of circulating monocytes is protective. On the other hand, depletion of macrophages several days after ischemic insult significantly delays tubular cell proliferation and recovery of renal function. Macrophages display significant plasticity and can adopt different phenotypes depending on their environment. Pro-inflammatory (M1) macrophages promote renal injury early during reperfusion. Alternatively-activated (M2) macrophages stimulate renal recovery and regeneration after the acute inflammatory phase of AKI subsides. There is evidence that M1-like macrophages that initially promote inflammation and renal injury switch phenotype in situ to M2-like macrophages that promote repair and regeneration of the kidney. However, prolonged macrophage activation and persistence in the recovering kidney may foster the development of fibrosis. Several key mediators, produced by renal tubular epithelial cells that encourage the macrophage phenotype shift have been identified. Similarly, some proteins made and released by macrophages that influence renal recovery and regeneration have also been discovered. This is a rapidly advancing area of AKI research that promises to reveal novel therapeutic possibilities. Suggested Reading: 1. Nelson, P. J., A. J. Rees, M. D. Griffin, J. Hughes, C. Kurts and J. Duffield The renal mononuclear phagocytic system. J Am Soc Nephrol. 23: Day, Y. J., L. Huang, H. Ye, J. Linden and M. D. Okusa Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages. Am J Physiol Renal Physiol. 288: F Li, L., L. Huang, S. S. Sung, A. L. Vergis, D. L. Rosin, C. E. Rose, Jr., P. I. Lobo and M. D. Okusa The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury. Kidney Int. 74: Lee, S., S. Huen, H. Nishio, S. Nishio, H. K. Lee, B. S. Choi, C. Ruhrberg and L. G. Cantley Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 22:

34 AKI & CRRT Lech, M., R. Grobmayr, M. Ryu, G. Lorenz, I. Hartter, S. R. Mulay, H. E. Susanti, K. S. Kobayashi, R. A. Flavell and H. J. Anders Macrophage phenotype controls long-term AKI outcomes--kidney regeneration versus atrophy. J Am Soc Nephrol. 25: Zhang, M. Z., B. Yao, S. Yang, L. Jiang, S. Wang, X. Fan, H. Yin, K. Wong, T. Miyazawa, J. Chen, I. Chang, A. Singh and R. C. Harris CSF-1 signaling mediates recovery from acute kidney injury. J Clin Invest. 122: Lin, S. L., B. Li, S. Rao, E. J. Yeo, T. E. Hudson, B. T. Nowlin, H. Pei, L. Chen, J. J. Zheng, T. J. Carroll, J. W. Pollard, A. P. McMahon, R. A. Lang and J. S. Duffield Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A. 107: Huen, S. C., L. Huynh, A. Marlier, Y. Lee, G. W. Moeckel and L. G. Cantley GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury. J Am Soc Nephrol. 26: Huen, S. C. and L. G. Cantley Macrophage-mediated injury and repair after ischemic kidney injury. Pediatr Nephrol. 30:

35 PW1 Models of AKI Leading to CKD Tuesday, February 16, 10:55-11:15 Manjeri Venkatachalam MBBS AKI & CRRT 2016 Educational Objectives: 1. Outline the factors that underlie defective recovery from AKI and discuss the possible tubule based mechanisms that lead to nephron loss during the AKI-CKD transition 2. Discuss the merits and demerits of rat and murine models for AKI transitioning to CKD. Point out the lack of AKI animal models that closely resemble AKI in the human and therefore the lack of suitable animal models for CKD development after human AKI. 3. Discuss the usefulness of delayed graft function (DGF) after human kidney transplantation as a model for CKD development after AKI Content Description: The transition of acute kidney injury to chronic kidney disease has major clinical significance. Subsets of dedifferentiated proliferating tubules recovering from AKI undergo pathological growth arrest, fail to redifferentiate and become atrophic. These abnormal tubules exhibit persistent, unregulated and progressively increasing profibrotic signaling along multiple pathways. Why some tubules damaged by AKI become atrophic and then give rise to fibrosis while others recover completely is an important unanswered question. Particularly noteworthy in the AKI-CKD transition and subsequent progression are epithelial pathologies that prevent tubule recovery, the cellular biology of fibrosis and the significance of renal mass reduction by prior CKD. Regardless of other considerations, if injury is severe and attended by extensive death of tubule cells, AKI invariably leads to tubule atrophy and fibrosis, as shown by animal studies and biopsies performed long after human AKI. Experimental contexts in which the AKI-CKD transition has been documented include rat and mouse models of bilateral kidney ischemia, unilateral ischemia with other kidney intact, unilateral ischemia with contralateral nephrectomy, subtotal nephrectomy followed by ischemic AKI in rats, unilateral ischemia with contralateral nephrectomy in pigs, AKI induced by xenobiotics such as uranyl ions, mercury, cisplatin and folic acid in rats and mice, and selective proximal tubule injury by diphtheria toxin in mice. The histopathology of CKD has been seen in human kidneys that have recovered from AKI and in kidneys that undergo AKI following transplantation and delayed graft function. Sustained reductions of renal blood flow caused by vasoconstriction and microvascular defects prevent complete recovery from AKI and favor transition to CKD. More importantly, microvascular defects appear to be causally related to the development of hypertension after the AKI-CKD transition that in turn favors progressive kidney damage by hemodynamic mechanisms. Species and strain differences need to be considered when modeling the AKI to CKD.transition. Suggested Reading: Hsu CY: Yes, AKI truly leads to CKD. J Am Soc Nephrol 23: , 2012 Chawla LS, Eggers PW, Star RA, Kimmel PL: Acute kidney injury and chronic kidney disease as interconnected syndromes.nengl J Med 371: 58 66, 2014 Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK: Acute kidney injury:a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol 298: F1078 F1094,

36 AKI & CRRT 2016 Finn WF: Recovery from Acute Renal Failure, edited by Lazarus JMBBM, New York, Churchill Livingstone, 1993, pp Polichnowski AJ, Lan R, Geng H, Griffin KA, Venkatachalam MA, Bidani AK: Severe renal mass reduction impairs recovery and promotes fibrosis after AKI. J Am Soc Nephrol 25: , 2014 Basile DP: Rarefaction of peritubular capillaries following ischemic acute renal failure: A potential factor predisposing to progressive nephropathy. Curr Opin Nephrol Hypertens 13: 1 7, 2004 Duffield JS: Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest 124: , 2014 Bonventre JV, Yang L: Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 121: , 2011 Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression. Venkatachalam MA, Weinberg JM, Kriz W, Bidani AK. J Am Soc Nephrol Aug;26(8):

37 AKI & CRRT 2016 PW1 Insights Into the Mechanisms of the AKI to CKD Continuum Tuesday, February 16, 11:35-11:55 Motoko Yanagita MD, PhD Educational Objectives: 1 Understand the epidemiology of AKI to CKD continuum. 2 Discuss the possible mechanism of AKI to CKD continuum. Content Description: AKI is now considered to increase the risk of developing chronic kidney disease (CKD) and end-stage renal disease, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers several features of CKD. Recently we generated a mouse strain expressing inducible Cre recombinase in proximal tubules (Ndrg1CreERT2 mice), in which Cre is activated by the administration of tamoxifen at the desired time point. Using this mouse strain and another mouse strain expressing diphtheria toxin receptor under the control of Cre recombinase (idtr mice), we generated a novel mouse model to induce proximal tubulespecific injury. Administration of high-dose diphtheria toxin (DT) faithfully causes severe proximal tubule-specific injury, associated with interstitial fibrosis and reduction of Epo production. Mild proximal tubule injury from a single hit triggers reversible fibrosis, whereas repeated mild injuries cause sustained interstitial fibrosis, inflammation, glomerulosclerosis and atubular glomeruli. Proximal tubule-specific injury also triggers distal tubule injury, implying the proximal-distal tubule crosstalk. Our data provide new evidence that proximal tubule injury triggers several features of CKD. Suggested Reading: 1. Okusa MD, Rosner MH, Kellum JA, Ronco C: Acute Dialysis Quality Initiative XIII Workgroup: Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKI. J Am Soc Nephrol. 27:44-8, Vincent IS, Okusa MD: Biology of renal recovery: molecules, mechanisms, and pathways. Nephron Clin Pract. 127:10-4, Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 81: , Ishani A, Nelson D, Clothier B, Schult T, Nugent S, Greer N, Slinin Y, Ensrud KE: The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med 171: , Grgic I, Campanholle G, Bijol V, Wang C, Sabbisetti VS, Ichimura T, Humphreys BD, Bonventre JV: Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis. Kidney Int 82: , Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, Yamamura K, Nagoshi N, Shibata S, Rao TN, Fehling HJ, Fukatsu A, Minegishi N, Kita T, Kimura T, Okano H, Yamamoto M, Yanagita M: Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest 121: , Endo T, Nakamura J, Sato Y, Asada M, Yamada R, Takase M, Takaori K, Oguchi A, Iguchi T, Higashi AY, Ohbayashi T, Nakamura T, Muso E, Kimura T, Yanagita M: Exploring the origin and limitations of kidney regeneration. J Pathol 236: , Takaori K, Nakamura J, Yamamoto S, Nakata H, Sato Y, Takase M, Nameta M, Yamamoto T, Economides AN, Kohno K, Haga H, Sharma K, Yanagita M: Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis. J Am Soc Nephrol in press. 36

38 PW1 Role of Complement in Acute Kidney Injury Tuesday, February 16, 1:35-1:55 Joshua Thurman MD AKI & CRRT 2016 Educational Objectives: -Possess a general understanding of the complement cascade -Describe the molecular mechanisms that cause complement activation during acute kidney injury -Understand the downstream pro-inflammatory effects of complement activation during acute kidney injury Content Description: The complement system is activated in the renal tubulointerstitium during the development of acute kidney injury (AKI). Work in animal models and human samples has demonstrated that complement activation in AKI occurs through the alternative pathway, and does not require immunoglobulin. Once activated, the complement system causes direct injury of tubular epithelial cells and generates anaphylatoxins and chemokines. Therapeutic complement inhibitors may attenuate AKI and prevent systemic inflammation in patients who develop AKI. Suggested Reading: 1. McCullough JW, Renner B, and Thurman JM. The role of the complement system in acute kidney injury. Seminars in nephrology. 2013;33(6): Fuquay R, Renner B, Kulik L, McCullough JW, Amura C, Strassheim D, Pelanda R, Torres R, and Thurman JM. Renal ischemia-reperfusion injury amplifies the humoral immune response. J Am Soc Nephrol. 2013;24(7): Thurman JM. Complement in kidney disease: core curriculum Am J Kidney Dis. 2015;65(1): Thurman JM, Ljubanovic D, Royer PA, Kraus DM, Molina H, Barry NP, Proctor G, Levi M, and Holers VM. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. The Journal of clinical investigation. 2006;116(2): Peng Q, Li K, Smyth LA, Xing G, Wang N, Meader L, Lu B, Sacks SH, and Zhou W. C3a and C5a promote renal ischemia-reperfusion injury. J Am Soc Nephrol. 2012;23(9):

39 AKI & CRRT 2016 PW1 Remote Ischemic Preconditioning: Bench to Bedside and Back Tuesday, February 16, 2:15-2:35 John A. Kellum MD Educational Objectives: To review current evidence for the effect of Remote Ischemic Preconditioning (RIPC) on the kidney To discuss possible mechanisms To consider future directions for personalized renal protection Content Description: Potential mechanisms for the effects seen with RIPC include humoral and neural triggers resulting in end organ protection to ischemia at a remote site. The dominant mechanism likely differs depending on the organ system involved. The use of timed blood pressure cuff inflations has been correlated with improved cardiac and renal biomarker levels in some patients while other investigations have shown no beneficial effect. This may be due in part to differences in study protocols, sizes, and the risk categories of the patients studied. Ongoing and future large multicenter trials investing the use of RIPC in stratified patient risk groups, potentially through the use of biomarkers, could help to determine if this long studied concept is ready for clinical use and if so, in which population. Suggested Reading: 1.Zarbock A, Schmidt C, Van Aken H, et al.: Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial.. JAMA 2015; 313: Zarbock A, Kellum JA: Remote ischemic preconditioning and protection of the kidney - a novel therapeutic option. Crit Care Med Meybohm P, Bein B, Brosteanu O, et al.: A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med 2015; 373: Hausenloy DJ, Candilio L, Evans R, et al.: Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 2015; 373: Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74:

40 PW2 AKI & CRRT 2016 Practice Based Learning In CRRT: The Science and the Art Educational Objectives: Describe the underlying concepts and review the process of decision making for choice of CRRT therapy components and their implementation Obtain hands on experience in machine set-up, troubleshooting, prescription and delivery Utilize the tools provided to manage complex cases with CRRT Content Description: This workshop is designed to provide participants with the knowledge and understanding for decision making for the effective utilization of CRRT to manage critically ill patients. The morning session will consist of a pre-test followed by didactics on the fundamental practical aspects of CRRT. During the afternoon session the participants will apply and expand their knowledge by participating in hands-on workshops covering the practical aspects of running of CRRT. At registration the participants will need to sign up for either the afternoon pediatric hands-on workshop or the adult rotating hands-on workshop. In the adult hands-on workshop, participants will be allocated to teams of 6 to 8. Each team will rotate through four interactive case simulations and role-playing with faculty. The four (4) sessions will be 45 minutes in length and will occur simultaneously. Each session will be repeated 4 times so teams can rotate through each session in order to maximize the learning opportunity. Teams rotate during 5 minute breaks between sessions. The 4 sessions consist of CRRT prescription/order sets, CRRT anticoagulation, CRRT dose/fluids/antibiotics, and CRRT circuit trouble-shooting/alarms/connections. In the pediatric hands-on workshop, participants will cover similar topics with a pediatric emphasis in a one 2-hour session. All the participants will then re-convene after the hands-on portion and participate in decision making through an interactive clinical case. They will then finish the session with a post-test. Suggested Reading: Reference recommendations will be giving during the workshop. 39

41 AKI & CRRT 2016 PW2 Pre-Course Test Tuesday, February 16, 8:00-8:45 Ashita Tolwani MD Educational Objectives: Administer a pre-test to assess the baseline knowledge base of the participants. Administer the same questions as a post-test at the end of the workshop to assess the participants improvement in knowledge. Discuss the answers with detailed explanations at the end of the workshop. Content Description: A CRRT pre and post-test will be used to assess the knowledge base of the participants. The test consists of 15 questions and will be administered in the morning prior to the start of the workshop. The same test will be administered at the end of the workshop to assess the participants improvement after going through the workshop. The answers will be discussed at the end of the workshop. Suggested Reading: KDIGO clinical practice guidelines for acute kidney injury. KI 2012 Tolwani A. Continuous renal replacement therapy for acute kidney injury. N Engl J Med Dec 27;367(26): doi: /NEJMct Review. PMID: Palevsky PM. Renal replacement therapy in acute kidney injury. Adv Chronic Kidney Dis Jan;20(1): doi: /j.ackd Review. PMID: Vijayan A, Palevsky PM. Dosing of renal replacement therapy in acute kidney injury. Am J Kidney Dis Apr;59(4): doi: /j.ajkd Review.PMID: Villa G, Ricci Z, Ronco C. Renal Replacement Therapy. Crit Care Clin Oct;31(4): doi: /j.ccc Ronco C, Ricci Z, De Backer D, et al. Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care Apr 6;19:146. doi: /s Galvagno SM, Hong CM, Lissauer ME, et al. Practical considerations for the dosing and adjustment of continuous renal replacement therapy in the intensive care unit. Journal of Critical Care 28 (2013) Morabito S, Pistolesi V, Tritapepe L, et al. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol Dec 5;9(12): doi: /CJN Honoré PM, De Waele E, Jacobs R, et al. Nutritional and metabolic alterations during continuous renal replacement therapy. Blood Purif. 2013;35(4): doi: / Wiesen P, Van Overmeire L, Delanaye P, et al. Nutrition disorders during acute renal renal failure and renal replacement therapy. JPEN J Parenter Enteral Nutr Mar;35(2): doi: / Review.PMID:

42 AKI & CRRT 2016 PW2 AKI and Patient Selection for CRRT Tuesday, February 16, 8:45-9:25 Jorge Cerda MD, FACP, FASN Educational Objectives: At the end of the session, participants will be able to 1. Describe the patient characteristics that define the most appropriate modality of renal replacement therapy in AKI 2. Discuss the impact of renal replacement modality on hemodynamic stability 3. Ennumerate the evidence currently available on the impact of timing of renal replacement initiation on patient outcomes 4. Describe the importance of fluid overload on AKI patient outcomes Content Description: When confronted with the need to apply renal replacement therapies, physicians must go through a series of complex decisions in an evidence-supported fashion. This presentation reviews and summarizes current recommendations on the use of renal replacement therapies in the management of severe acute kidney injury. Main aspects discussed include choice of renal replacement modality; timing of initiation; dose prescribed and delivered; and fluid management. The article also discusses the long-term impact of renal replacement therapies on kidney function recovery. Suggested Reading: Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med Dec 27;367(26): Macedo E, Mehta RL. Tailored therapy: matching the method to the patient. Blood Purif. 2012;34(2): Cerdá J, Tolwani AJ, Warnock DG. Critical care nephrology: management of acid-base disorders with CRRT. Kidney Int Jul;82(1):9-18. Cerdá J, Ronco C. Modalities of continuous renal replacement therapy: technical and clinical considerations. Semin Dial. 2009;22(2): Shah, S, Cerda J. Acute kidney injury in special circumstances. Chapter 2, pp Cerda J. Acute kidney injury in sepsis. Chapter 3, pp Cerda J. Pharmacologic therapy in acute kidney injury. Chapter 7, pp Cerda J, Ronco, C. Choosing a renal replacement therapy in acute kidney injury. Chapter 10, pp In: Handbook of Renal and Metabolic Disorders. J Kellum and J Cerda, Editors. Pittsburgh Critical Care Medicine Series. Oxford University Press Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press, 2009 Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. Mauro Neri, Jorge Cerda, Francesco Garzotto, Gianluca Villa, Claudio Ronco: Nomenclature for Renal Replacement Therapy in Acute Kidney Injury In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press, In 41

43 AKI & CRRT 2016 press, 2015 PW2 CRRT: The Technical Questions - Modality, A/C, Solutions, Dose Tuesday, February 16, 9:25-10:10 Ashita Tolwani MD Educational Objectives: Review the differences between CRRT modalities Describe the calculations for solute clearance for each CRRT modality Discuss citrate anticoagulation, CRRT solution composition, and adequate dose Content Description: Ideal CRRT should run continuously and provide optimal volume control, adequate solute clearance, and correction of acid-base/electrolyte derangements. Providing optimum CRRT involves understanding the differences in the technical aspects of the CRRT modalities with respect to solute clearance, solutions, anticoagulation, and delivered dose. Anticoagulation is often needed to decrease circuit clotting and therefore minimize time off CRRT. Citrate anticoagulation has become the preferred anticoagulant. This lecture will describe the calculations for solute clearance for each CRRT modality, review dose adequacy, assess the effect of different CRRT modalities on the delivered dose, and discuss citrate anticoagulation and solutions. Suggested Reading: KDIGO clinical practice guidelines for acute kidney injury. KI 2012 Tolwani A. Continuous renal replacement therapy for acute kidney injury. N Engl J Med Dec 27;367(26): doi: /NEJMct Review. PMID: Palevsky PM. Renal replacement therapy in acute kidney injury. Adv Chronic Kidney Dis Jan;20(1): doi: /j.ackd Review. PMID: Vijayan A, Palevsky PM. Dosing of renal replacement therapy in acute kidney injury. Am J Kidney Dis Apr;59(4): doi: /j.ajkd Review.PMID: Villa G, Ricci Z, Ronco C. Renal Replacement Therapy. Crit Care Clin Oct;31(4): doi: /j.ccc Ronco C, Ricci Z, De Backer D, et al. Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care Apr 6;19:146. doi: /s Galvagno SM, Hong CM, Lissauer ME, et al. Practical considerations for the dosing and adjustment of continuous renal replacement therapy in the intensive care unit. Journal of Critical Care 28 (2013) Morabito S, Pistolesi V, Tritapepe L, et al. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol Dec 5;9(12): doi: /CJN Honoré PM, De Waele E, Jacobs R, et al. Nutritional and metabolic alterations during continuous renal replacement therapy. Blood Purif. 2013;35(4): doi: / Wiesen P, Van Overmeire L, Delanaye P, et al. Nutrition disorders during acute renal renal failure and renal replacement therapy. JPEN J Parenter Enteral Nutr Mar;35(2): doi: 42

44 AKI & CRRT / Review.PMID: PW2 Developing, Implementing, Maintaining and Financial Aspects of CRRT Tuesday, February 16, 11:35-12:00 Jorge Cerda MD, FACP, FASN Educational Objectives: 1. Describe the organizational characteristics of a CRRT program 2. Discuss the ethical implications of CRRT treatment in the critically ill patient with AKI 3. Ennumerate the financial implications of the treatment of critically ill patients with AKI Content Description: When confronted with the need to apply renal replacement therapies, physicians must go through a series of complex decisions in an evidence-supported fashion. This presentation reviews and summarizes current recommendations on the use of renal replacement therapies in the management of severe acute kidney injury. Main aspects discussed include choice of renal replacement modality; timing of initiation; dose prescribed and delivered; and fluid management. The session also discusses the long-term impact of renal replacement therapies on kidney function recovery. The workshop will focus on the organizational, ethical and financial implications of the treatment of critically ill patients with AKI Suggested Reading: Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med Dec 27;367(26): Cerdá J, Tolwani AJ, Warnock DG. Critical care nephrology: management of acid-base disorders with CRRT. Kidney Int Jul;82(1):9-18. Cerdá J, Ronco C. Modalities of continuous renal replacement therapy: technical and clinical considerations. Semin Dial. 2009;22(2): Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. Mauro Neri, Jorge Cerda, Francesco Garzotto, Gianluca Villa, Claudio Ronco: Nomenclature for Renal Replacement Therapy in Acute Kidney Injury In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press, In press, 2015 Shah, S, Cerda J. Acute kidney injury in special circumstances. Chapter 2, pp Cerda J. Acute kidney injury in sepsis. Chapter 3, pp Cerda J. Pharmacologic therapy in acute kidney injury. Chapter 7, pp Cerda J, Ronco, C. Choosing a renal replacement therapy in acute kidney injury. Chapter 10, pp In: Handbook of Renal and Metabolic Disorders. J Kellum and J Cerda, Editors. Pittsburgh Critical Care Medicine Series. Oxford University Press Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press,

45 AKI & CRRT 2016 PW2 SESSION 1 CRRT Prescription/Order Sets/Documentation Tuesday, February 16, 1:15-3:30 Jorge Cerda MD, FACP, FASN Educational Objectives: 1. Discuss the process of setting up a CRRT prescription utilizing different variations in the CRRT modality 2. Ennumerate the impact of different CRRT prescriptions on prescribed and delivered dialysis dose 3. Demonstrate the calculations necessary to quantitate prescribed and delivered dialysis dose, solutions and filtration fraction Content Description: When confronted with the need to apply renal replacement therapies, physicians must go through a series of complex decisions in an evidence-supported fashion. This presentation reviews and summarizes current recommendations on the use of renal replacement therapies in the management of severe acute kidney injury. Main aspects discussed include choice of renal replacement modality; timing of initiation; dose prescribed and delivered; and fluid management. The session focuses on the practical application of different CRRT modalities and actual calculations of dose, prescription vs. delivery of dialysis dose, choice of different solutions and pitfalls. Suggested Reading: Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med Dec 27;367(26): Cerdá J, Tolwani AJ, Warnock DG. Critical care nephrology: management of acid-base disorders with CRRT. Kidney Int Jul;82(1):9-18. Cerdá J, Ronco C. Modalities of continuous renal replacement therapy: technical and clinical considerations. Semin Dial. 2009;22(2): Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. Mauro Neri, Jorge Cerda, Francesco Garzotto, Gianluca Villa, Claudio Ronco: Nomenclature for Renal Replacement Therapy in Acute Kidney Injury In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press, In press, 2015 Shah, S, Cerda J. Acute kidney injury in special circumstances. Chapter 2, pp Cerda J. Acute kidney injury in sepsis. Chapter 3, pp Cerda J. Pharmacologic therapy in acute kidney injury. Chapter 7, pp Cerda J, Ronco, C. Choosing a renal replacement therapy in acute kidney injury. Chapter 10, pp In: Handbook of Renal and Metabolic Disorders. J Kellum and J Cerda, Editors. Pittsburgh Critical Care Medicine Series. Oxford University Press Cerda J, Ronco C. Choosing a Renal Replacement Therapy in Acute Kidney Injury. CRRT Modalities: Technical and Clinical Considerations. In: Continuous Renal Replacement Therapies. J Kellum, R Bellomo, C Ronco, Editors Oxford Press,

46 AKI & CRRT 2016 PW2 SESSION 2 Circuit, Anticoagulation, Citrate Protocols Tuesday, February 16, 1:15-3:30 Ashita Tolwani MD Educational Objectives: 1. Learn how to set up citrate anticoagulation for CVVH, CVVHD, CVVHDF using Prismaflex and NxStage CRRT devices. 2. Determine appropriate labs to obtain for citrate anticoagulation and adequacy of anticoagulation. 3. Trouble-shoot anticoagulation issues based on CRRT parameters, labs, and patient clinical condition Content Description: In this interactive hands-on simulation, the participants will decide on the appropriate CRRT anticoagulation protocol after being presented with a clinical case scenario. Participants will determine the following as a team: *CRRT modality *Citrate solution and corresponding CRRT solutions *CRRT prescription (blood flow rate, citrate rate, pre and/or post replacement fluid rate if needed, dialysate rate if needed, fluid removal rate, calcium infusion rate) Participants will also calculate prescribed dose based on their choices and program the prescription into the CRRT device. They will demonstrate the appropriate placement of CRRT solutions on the device, and demonstrate appropriate sites for obtaining labs for citrate anticoagulation. After initial prescription set up, participants will be given a set of repeat labs and will have to troubleshoot deranged ionized calcium and/or electrolyte results. Suggested Reading: Morabito S, Pistolesi V, Tritapepe L, et al. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol Dec 5;9(12): doi: /CJN Tolwani A, Wille KM. Advances in continuous renal replacement therapy: citrate anticoagulation update. Blood Purification. 2012;34(2):88-93.doi: / Epub 2012 Oct 24 Davenport A, Tolwani A. Citrate anticoagulation for continuous renal replacement therapy (CRRT) in patients with acute kidney injury admitted to the intensive care unit. NDT Plus (2009) 2: Tolwani A, Wille KM. Anticoagulation for continuous renal replacement therapy. In: UpToDate, Schwab, SJ (Ed), UpToDate, Waltham, MA. 45

47 AKI & CRRT 2016 PW2 SESSION 4 Monitoring, Alarms and Connections with Other Therapies Tuesday, February 16, 1:15-3:30 Ian Baldwin RN, PhD, FACCCN Educational Objectives: 1.Review the CRRT circuit for common pressure and data measurements. 2.Define and understand the normal readings and ranges for these pressures. 3.Describe what measurements are useful to record and what they can provide for clinical care, troubleshooting and optimal use of CRRT. Content Description: The CRRT circuit commonly enables measurement of the following pressures or variables. An awareness of these variables and their meaning alone or in groups provide detailed understand of the CRRT treatment for normal and abnormal function. Early recognition and response to alarms provides safety and optimal care with CRRT. Circuit pressure/ variable Normal range Clinical association Access pressure (e.g. Pa) Negative 50±10 mmhg Is the negative pressure due to suction of blood from the access device. Faster blood flow and or access obstruction, causes flow failure and an alarm state. Pre-filter pressure (e.g. Pin) Positive 100 ± 50 mmhg Is measured after the blood pump and is increased as the filter clots or clogs. Is affected by blood flow (ml/min.) setting. Trans-membrane pressure (TMP)Positive mmhg Reflects the average pressure before and after the filter minus the pressure across the filter due to filtration. Increases with clotting. Venous pressure (e.g. Pv)Positive mmhg Pressure prior to blood return to the patient commonly from the venous bubble trap. Clotting here, or access obstruction increases the pressure. Air detected A safety alarm Presence of air bubbles in the chamber before blood return to the patient. Fluids temperature 37 ±3 Celsius Is the temperature for the dialysate / substitution fluids with heating. Blood leak detection A safety alarm Membrane or filter failure and red cells allowed into the waste. A crisis alarm. Fluid balance error A safety alarm The scales weighing the fluids as a means of controlling the fluid balance (1gm=1mL) detect an unexpected difference in weight from prescribed. Associated with service and or technical require- Software code errors Safety or advisory alarms ments for the CRRT machine. Suggested Reading: 46

48 AKI & CRRT Zhang L, Baldwin I, Zhu G, Tanaka A and Bellomo R Automated electronic monitoring of circuit pressures during continuous renal replacement therapy : a technical report. Crit care and Resuscitation. Vol. 17 No. 1 March. 2.Boyle M and Baldwin I Understanding the Continuous Renal Replacement Therapy circuit for Acute Renal failure support; A quality issue in the Intensive Care Unit. AACN Advanced Critical Care Vol. 21 No. 4 pp Baldwin I and Fealy N Nursing for renal replacement therapies in the Intensive Care Unit: historical, educational, and protocol review. Blood Purification. 27: Baldwin I and Fealy N Clinical nursing for the application of renal replacement therapies in the Intensive Care Unit. Seminars in Dialysis. Vol. 22 No. 2. pp Bashaw S, Baldwin I, Fealy N, Bellomo R Fluid Balance Error in Continuous Renal Replacement Therapy: A Technical Note. International Journal of Artificial Organs. Vol. 30 No. 5 pp Kellum J, Bellomo R, Ronco C Continuous Renal Replacement Therapy. Oxford Press, New York. Chapter

49 PW2 PEDIACTRIC SESSION Tuesday, February 16, 1:15-3:30 David Askenazi MD, MSPH AKI & CRRT 2016 Educational Objectives: Following this session, the participant should be able to: 1. Describe the epidemiology of acute kidney injury in neonates, including the outcomes of small children who receive CRRT. 2. Understand the special technical considerations associated with performing neonatal CRRT 3. Understand the general indications for neonatal CRRT, with a special focus on inborn errors of metabolism 4. Discuss new technology for neonatal CRRT. Content Description: For many years any form of dialysis support was considered too difficult for neonates; for those centers that would provide renal replacement, peritoneal dialysis was considered the only viable modality. Over the past few decades, however, the use of CRRT in the neonatal intensive care unit has expanded substantially. Performing CRRT for newborn patients presents unique challenges. There are significant technical barriers to performing CRRT in neonates and risks may be magnified when devices and materials designed for use in adults are adapted to the care of very small patients. This session will discuss the epidemiology of acute kidney injury in the newborn, demographics and outcomes in neonates receiving CRRT, indications for CRRT including its use in the management of inborn errors of metabolism, and technical approaches to the procedure with emphasis on the differences from therapy as used in older children and adults. In addition, we will discuss new technologies designed specifically for the care of the neonate who requires CRRT. We look forward to an interactive session where members of the audience will share their own experiences, allowing all participants to gain further knowledge1. Suggested Reading 1. Askenazi DJ, et. al.. Continuous Renal Replacement Therapy for Children 10 kg: A Report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry. J Pediatr Oct Symons JM et al. Continuous renal replacement therapy in children up to 10 kg. Am J Kid Dis (2003) 18: Askenazi DJ et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr (2011) 159: Askenazi DJ et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med (2011) 12:e1-e6. 48

50 AKI & CRRT Brophy PD et al. AN-69 membrane reactions are ph-dependent and preventable. Am J Kid Dis (2001) 38: Hackbarth RM, et. al.. Zero balance ultrafiltration in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection. Pediatr Nephrol Sep;20(9): McBryde KD et al. Renal replacement therapy in the treatment of confirmed or suspected inborn errors of metabolism. J Pediatr (2006) 8. Pasko DA et al. Pre dialysis of blood prime in continuous hemodialysis normalizes ph and electrolytes. Pediatr Nephrol (2003) 18: Picca S et al. Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators. Pediatr Nephrol (2001) 16: Schaefer F et al. Dialysis in neonates with inborn errors of metabolism. Nephrol Dial Transplant (1999) 14: Askenazi D, Ingram D, White S, et al. Smaller circuits for smaller patients: improving renal support therapy with Aquadex. Pediatric nephrology (Berlin, Germany)

51 AKI & CRRT 2016 A01 Using Kidney Biomarkers for AKI 1: Risk Assessment, Diagnosis and Staging Wednesday, February 17, 8:00-9:30 Jay Koyner MD Educational Objectives: 1. To discuss why newer biomarkers of AKI are needed and how they have been clinically investigated to date. 2. To understand how biomarkers may be used to improve AKI clinical risk assessment in hospitalized patients 3. To identify studies that has investigated the ability of biomarkers to diagnosis AKI in a variety of clinical settings (e.g. cardiac surgery, sepsis, nephron-toxin etc ) 4. To discuss how biomarkers may be used to assist in the staging of AKI not only differentiating AKI severity (Stage 1 from stage 3) or the need for RRT but also discussing the role for predicting renal recovery. Content Description: In this session we will start by setting the stage for why biomarkers of AKI are needed and discuss the basics around how they have been tested. Briefly reviewing concepts such as the ROC-AUC as well as the failings of the current gold standard, serum creatinine and urine output. We will discuss the utility of using biomarkers (functional and damage) to improve AKI risk assessment. This can take the form of pre-operative biomarker measurements but also using biomarkers (alone or in combination) after the AKI insult. These concepts, as well as the concept of the Renal Angina Index and other risk assessment scores will be extensively discussed. We will then review some of the results from the larger multicenter trials which demonstrated that biomarkers of AKI are strongly associated with the future development of AKI (defined by changes in creatinine or urine output). As part of this we will specifically discuss the results of the TRIBE-AKI, Sapphire, EARLY-ARF and other large scale multi-center validation studies. We will cover a diversity of clinical settings (cardiac surgery, sepsis, emergency department) but also different patient populations (e.g. adult vs. pediatric cohorts). Additionally, we will discuss how in some of these same cohorts, as well as in other publications, biomarkers have demonstrated the ability to predict AKI severity (e.g. Stage 3 AKI) or the need for renal replacement therapy. We will discuss the handful of papers that have looked at biomarkers and AKI recovery. Suggested Reading: 1 ) Kidney Int Mar;85(3): doi: /ki Epub 2013 Oct 9. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Murray PT1, Mehta RL2, Shaw A3, Ronco C4, Endre Z5, Kellum JA6, Chawla LS7, Cruz D8, Ince C9, Okusa MD10; ADQI 10 workgroup. 2) J Am Soc Nephrol Sep;22(9): doi: /ASN Epub 2011 Aug 11. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. Parikh CR1, Coca SG, Thiessen-Philbrook H, Shlipak MG, Koyner JL, Wang Z, Edelstein CL, Devarajan P, Patel UD, Zappitelli M, Krawczeski CD, Passik CS,Swaminathan M, Garg AX; TRIBE-AKI Consortium. 3) J Am Soc Nephrol Sep;22(9): doi: /ASN Epub 2011 Aug 11. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. 50

52 AKI & CRRT 2016 Parikh CR1, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD;TRIBE-AKI Consortium. 4) J Am Soc Nephrol May;23(5): doi: /ASN Epub 2012 Mar 1. Biomarkers predict progression of acute kidney injury after cardiac surgery. Koyner JL1, Garg AX, Coca SG, Sint K, Thiessen-Philbrook H, Patel UD, Shlipak MG, Parikh CR; TRIBE-AKI Consortium. 5) Crit Care Feb 6;17(1):R25. doi: /cc Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN,Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes-Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmelé T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG,Zacharowski K, Kellum JA. 6) Kidney Int Jun;77(11): doi: /ki Epub 2010 Feb 17. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Endre ZH1, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, Westhuyzen J, Celi LA,McGinley RJ, Campbell IJ, George PM. 7) Clin J Am Soc Nephrol Apr;9(4): doi: /CJN Epub 2014 Mar 27. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Basu RK1, Wang Y, Wong HR, Chawla LS, Wheeler DS, Goldstein SL. 8) Kidney Int Mar;85(3): doi: /ki Epub 2013 Sep 18. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Basu RK1, Zappitelli M2, Brunner L3, Wang Y4, Wong HR5, Chawla LS6, Wheeler DS1, Goldstein SL7. 9) Clin J Am Soc Nephrol Aug 7;10(8): doi: /CJN Epub 2015 Jun 5. Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving RRT. Pike F1, Murugan R2, Keener C1, Palevsky PM3, Vijayan A4, Unruh M5, Finkel K6, Wen X2, Kellum JA7; Biological Markers for Recovery of Kidney (BioMaRK) Study Investigators. 10) Clin J Am Soc Nephrol Aug;6(8): doi: /CJN Epub 2011 Jul 14 Urinary biomarkers and renal recovery in critically ill patients with renal support Srisawat N1, Wen X, Lee M, Kong L, Elder M, Carter M, Unruh M, Finkel K, Vijayan A, Ramkumar M, Paganini E, Singbartl K, Palevsky PM, Kellum JA. 51

53 B02 Strategies for Optimizing the CRRT Circuit (Access, Anticoagulation and Monitoring) Citrate Anticoagulation Wednesday, February 17, 8:00-9:30 David Askenazi MD, MSPH Educational Objectives: 1. Describe the epidemiology of acute kidney injury in neonates, including the outcomes of small children who receive CRRT. 2. Understand the special technical considerations associated with performing neonatal CRRT 3. Understand the general indications for neonatal CRRT, with a special focus on inborn errors of metabolism 4. Discuss new technology for neonatal CRRT. Content Description: For many years any form of dialysis support was considered too difficult for neonates; for those centers that would provide renal replacement, peritoneal dialysis was considered the only viable modality. Over the past few decades, however, the use of CRRT in the neonatal intensive care unit has expanded substantially. Performing CRRT for newborn patients presents unique challenges. There are significant technical barriers to performing CRRT in neonates and risks may be magnified when devices and materials designed for use in adults are adapted to the care of very small patients. This session will discuss the epidemiology of acute kidney injury in the newborn, demographics and outcomes in neonates receiving CRRT, indications for CRRT including its use in the management of inborn errors of metabolism, and technical approaches to the procedure with emphasis on the differences from therapy as used in older children and adults. In addition, we will discuss new technologies designed specifically for the care of the neonate who requires CRRT. We look forward to an interactive session where members of the audience will share their own experiences, allowing all participants to gain further knowledge1. Suggested Reading: AKI & CRRT Askenazi DJ, et. al.. Continuous Renal Replacement Therapy for Children 10 kg: A Report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry. J Pediatr Oct Symons JM et al. Continuous renal replacement therapy in children up to 10 kg. Am J Kid Dis (2003) 18: Askenazi DJ et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr (2011) 159: Askenazi DJ et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med (2011) 12:e1-e6. 5. Brophy PD et al. AN-69 membrane reactions are ph-dependent and preventable. Am J Kid Dis (2001) 38: Hackbarth RM, et. al.. Zero balance ultrafiltration in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection. Pediatr Nephrol Sep;20(9): McBryde KD et al. Renal replacement therapy in the treatment of confirmed or suspected inborn errors of metabolism. J Pediatr (2006) 8. Pasko DA et al. Pre dialysis of blood prime in continuous hemodialysis normalizes ph and elec- 52

54 AKI & CRRT 2016 trolytes. Pediatr Nephrol (2003) 18: Picca S et al. Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators. Pediatr Nephrol (2001) 16: Schaefer F et al. Dialysis in neonates with inborn errors of metabolism. Nephrol Dial Transplant (1999) 14: Askenazi D, Ingram D, White S, et al. Smaller circuits for smaller patients: improving renal support therapy with Aquadex. Pediatric nephrology (Berlin, Germany)

55 AKI & CRRT 2016 B02 Strategies for Optimizing the CRRT Circuit (Access, Anticoagulation and Monitoring) Citrate Anticoagulation Wednesday, February 17, 8:00-9:30 Ian Baldwin RN, PhD, FACCCN Educational Objectives: 1.To appreciate how important the vascular access catheter is for best CRRT. 2.To review different types of access catheters used for CRRT : in-vitro and in-vivo performance. 3.Identify aspects of care, maintenance, and troubleshooting for the vascular access to optimize CRRT systems. Content Description: This workshop presentation aims to provide participants with a focused review of the important relationship between the vascular access catheter and the CRRT extracorporeal circuit (EC). The access catheter and placement can be the most important aspect of optimizing circuit function. Key areas reviewed are : access catheter design profiles (lumen arrangement) and length (cm) the femoral site and how it may be the most reliable for blood flow in the ICU failure of the access and how this may be undetected, but is associated with premature failure or clotting Maintenance and troubleshooting concepts related to these points above can be very helpful for physicians prescribing treatment and nurses managing function of CRRT in the critical care. Quality data and evidence from more recent clinical studies will be presented to support the above statements, and suggests the femoral site is best for providing best practice CRRT. Suggested Reading: 1.Bellomo R, Martensson, J, Lo S,Kaukonen K-M, Cass A, Gallagher M for the RENAL study investigators and the Australian and New Zealand Intensive Care Clinical Trials Group Femoral access and delivery of continuous renal replacement therapy dose. Blood Purification.41: Zhang L, Baldwin I, Zhu G, Tanaka A and Bellomo R Automated electronic monitoring of circuit pressures during continuous renal replacement therapy : a technical report. Crit Care and Resuscitation. Vol. 17 No. 1 March. 3.In Byung, Nigel Fealy, Ian Baldwin, Rinaldo Bellomo Insertion side, body position and circuit life during continuous renal replacement therapy with femoral vein access. Blood Purification; 31: In Byung Kim, Fealy N, Baldwin I, Bellomo R Premature circuit clotting due to likely mechanical failure during Continuous Renal Replacement Therapy. Blood Purification. 30: Crosswell A, Brain M J, Roodenburg O Vascular access site influences circuit life in continuous renal replacement therapy. Critical Care and Resuscitation.; 16: Baldwin I and Bellomo R The relationship between blood flow, access catheter and circuit failure during CRRT; a practical review. Contributions to Nephrology, vol pp Canaud B, Formet C, Raynal N, Amigues L, Klouche K, Leray-Moragues H, and Beraud J-J Vascular access for extracorporeal renal replacement therapy in the intensive care unit. Contributions to Nephrology, vol pp Baldwin I, Bellomo R and Koch W Blood Flow reductions during Continuous Renal Replacement Therapy and Circuit Life. Intensive Care Medicine. 30: Baldwin I, Bellomo R, and Koch B A technique for the monitoring of blood flow during continuous hemofiltration. Intensive Care Med. 28 : Fealy N, Aitken L, du Toit E, Baldwin I. Continuous renal replacement therapy: current practice in Australian and New Zealand intensive care units. Critical Care and Resuscitation 2015; 17:

56 AKI & CRRT 2016 A08 Using Kidney Biomarkers for AKI 2: Differential Diagnosis, Interventions and Prognosis Wednesday, February 17, 10:00-11:30 Stuart L. Goldstein MD Educational Objectives: 1) Discuss how biomarkers can be used to differentiate between structural and functional AKI 2) Demonstrate the current state of utilizing biomarkers to guide therapy in patients with, or at risk for AKI 3) Identify studies that show how AKI biomarkers in the acute and chronic setting can lend insight into acute and chronic outcomes of mortality and chronic kidney disease Content Description: The second workshop session on AKI biomarkers will focus on both demonstrated and theoretical uses in the clinical setting. First, the data surrounding the use of biomarkers to differentiate between pre-renal (functional) and intrinsic (structural) AKI will be discussed. In addition, the addition of biomarkers to the classic serum creatinine and urine output based AKI diagnostic and severity definitions will be proposed. In the second talk, implementation of biomarkers into clinical pathways including identifying patients at greater risk of AKI (ICU patients, nephrotoxic medication exposure), and also directing interventional trials will be presented. Finally, the use of AKI biomarkers to predict important Major Adverse Kidney Events (MAKE) such as short term mortality and chronic kidney disease development will be highlighted. Very recent work demonstrating biomarker persistence many years after AKI will also be shown. Suggested Reading: 1) Endre ZH, Kellum JA, Di Somma S, Doi K, Goldstein SL, Koyner, JL, Macedo E, Mehta RL, Murray PT: Differential Diagnosis of AKI in Clinical Practice by Functional and Damage Biomarkers: Workgroup Statements from the Tenth Acute Dialysis Quality Initiative Consensus Conference. Contributions in Nephrology 182:30-44, ) Basu RK, Wong HR, Krawczeski CD, Wheeler DS, Manning PB, Chawla LS, Devarajan P, Goldstein SL: Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. Journal of the American College of Cardiology. 64: , ) Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL, Barasch J, Luft FC, Schmidt-Ott KM: Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes.kidney Int Aug;80(4): ) Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, Westhuyzen J, Celi LA, McGinley RJ, Campbell IJ, George PM: Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int Jun;77(11): ) Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM; Canadian Critical Care Trials Group: Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials Oct 5;14:320 6) Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Bennett MR, Kimmel PL, Seneff MG, Chawla LS: Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity.J Am Soc Nephrol Aug;26(8): ) Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, Haase M, Shi J, Kellum JA; Sapphire Investigators: Tissue Inhibitor Metalloproteinase-2 (TIMP-2) IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI. J Am Soc Nephrol Jul;26(7): ) Cooper DS, Claes D, Goldstein SL, Bennett MR, Ma Q, Devarajan P, Krawczeski CD: Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI).Clin J Am Soc Nephrol Nov 17. [epub] 55

57 B09 CRRT for the Experienced User 1 Wednesday, February 17, 10:00-11:30 Rolando Claure MD, FASN AKI & CRRT 2016 Educational Objectives: 1. Discuss RRT modality selection and transitions in patients with AKI. 2. Discuss KDIGO Guidelines recommendations regarding dose in CRRT and describe the different factors that affect CRRT dose in AKI. 3. Identify the gaps in current practice and propose an approach to ensure delivering a prescribed dose. Content Description: Controversy exists as to which is the optimal RRT modality for patients with AKI. In current clinical practice, the choice of the initial modality for RRT is primarily based on the availability of, and experience with, a specific treatment and on the patient s hemodynamic status. Transitions between CRRT and IHD are also frequent, mostly determined by the hemodynamic status of the patient or coagulation problems. Assessing and delivering dialysis dose in AKI is also an important issue in the management of critically ill patients. Most studies have focused on clearance of small molecules (blood urea nitrogen) as a marker of delivered dose and for establishing dose outcome relationships. Recent evidence has shown that other markers may also be important to consider, as acid base balance and fluid overload have emerged as important factors contributing to outcomes. In the first part of this workshop, we will first discuss modality selection and transitions in critically ill patients with AKI, then we will provide an evaluation of current approaches to prescribing and delivering dialysis dose in AKI, identify gaps in practice and propose an integrated approach to optimize dose delivery in dialysis with a goal to improve outcomes. Suggested Reading: 1. Overberger P, Pesacreta M, Palevsky PM: Management of renal replacement therapy in acute kidney injury: a survey of practitioner prescribing practices. Clin J Am Soc Nephrol 2: , RENAL Study Investigators. Renal replacement therapy for acute kidney injury in Australian and New Zealand intensive care units: a practice survey. Crit Care Resusc 2008; 10: Bagshaw SM, Berthiaume LR, Delaney A, et al. Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 2008; 36: Srisawat N, Lawsin L, Uchino S, et al. Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study. Crit Care 2010; 14: R KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012; Suppl 1: 2, Davenport A, Bouman C, Kirpalani A, Skippen P, Tolwani A, Mehta RL, Palevsky PM: Delivery of renal replacement therapy in acute kidney injury: what are the key issues? Clin J AmSocNephrol 3: , Davenport A, Farrington K: Dialysis dose in acute kidney injury and chronic dialysis. Lancet 375: , Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL; Program to Improve Care in Acute Renal Disease (PICARD) Study Group: Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 76: , Claure-Del Granado R, Macedo E, Chertow G et al. Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis. Clin J Am Soc Nephrol 6: , Claure-Del Granado R and Mehta RL. Assessing and delivering dialysis dose. Semin Dial 24:208-14,

58 B09 CRRT for the Experienced User 1 Wednesday, February 17, 10:00-11:30 Ian Baldwin RN, PhD, FACCCN AKI & CRRT 2016 Educational Objectives: 1.Appreciate how dose delivery can be difficult to achieve when frequent clotting and stopping treatment occurs with CRRT. 2.Review case examples such as ALF where fluid excess and solute control failed and how this context can be life threatening. 3.Identify both approaches to improving dose delivery and necessary monitoring to detect associated dose failure. Content Description: This workshop presentation aims to present case studies when frequent clotting occurs and dose delivery fails. This can be in association with acute liver failure when aberrant coagulation exists and conventional anticoagulation choices are excluded and or require modification. Fluid balance, brain oedema, acid base and solute and toxin load are difficult to control. Common questions associated are : The coagulation is abnormal, do I need to prescribe further anticoagulation? The filter is clotting despite use of anticoagulation; what should I do? Is the dose delivery failing, or is the patient sicker.how do I know? Suggested Reading: 1.Bellomo R, Martensson, J, Lo S,Kaukonen K-M, Cass A, Gallagher M for the RENAL study investigators and the Australian and New Zealand Intensive Care Clinical Trials Group Femoral access and delivery of continuous renal replacement therapy dose. Blood Purification.;41: Chua H R, Baldwin I, Bailey M, Subramaniam A, Bellomo R Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure. Journal of Critical care. Dec;27(6):744.e7-744.e15. 3.Armando T, and Mannucci M The coagulopathy of chronic liver disease. New England Journal of medicine. 365: M Haase, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Morgera S, Goehl H, Storr M, Boyce N, Neumayer H H B2 microglobulin removal and plasma albumin levels with high cut-off hemodialysis. International journal of artificial organs. Vol. 30 No. 5,. pp Agarwal B, Shaw S, Hari MS, et al Continuous renal replacement therapy (CRRT) in patients with liver disease: is circuit life different? J Hepatol;51: Gonwa T and Wadei H M The challenges of providing renal replacement therapy in de-compensated liver cirrhosis. Blood Purification. 33: Fealy N, Baldwin I, Bellomo R The effect of circuit down time on uraemic control during continuous veno-venous haemofiltration. Critical Care and Resuscitation 4:

59 AKI & CRRT 2016 D11 Managing Patients with Sepsis 1 : Pathophysiology, Diagnosis, Assessment, Resuscitation, Drug Management, Techniques for Disease Modification, Organ Support and Renal Protection Wednesday, February 17, 10:00-11:30 Geoffrey Fleming MD Educational Objectives: Educational Objectives 1) Describe the pathophysiology and etiology of sepsis with specific focus on the similarities and differences between Adult and Pediatric Septic Shock 2) Using the Surviving Sepsis Campaign Guidelines apply an algorithm of treatment for patients in a case based sepsis scenario with specific emphasis on the similarities between Adult and Pediatric Septic Shock. 3) Evaluate the role for adjunct therapies in the treatment of Adult and Pediatric Sepsis. Content Description: Content Description: Sepsis is the most frequent etiology of shock treated in both the Adult and Pediatric population and is responsible for a significant number of deaths annually. Published expert consensus guidelines exist regarding an algorithm for the treatment of septic shock including fluid resuscitation, inotropy and vasopressor support including therapeutic targets and clinical end-points. Key to effective management of septic shock includes an understanding of the pathophysiology and vascular biology of septic shock for appropriate application of therapeutic strategies. Adult and Pediatric sepsis are not identical with regards to etiology and pathophysiology and require specific attention to the similarities and differences in understanding management in both populations. This course will utilize case based strategies to highlight the outlined curriculum through both didactic and interactive learning strategies. References 1. Beale RJ, Hollenberg SM, Vincent J-L, Parrillo JE. Vasopressor and inotropic support in septic shock: An evidence-based review. Critical Care Medicine. Nov ;32(Supplement):S455-S Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Critical Care Medicine. Vol : Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic Support in Fluid-refractory Pediatric Septic Shock. PEDIATRICS. Aug ;102(2):e19-e Cohen J. The immunopathogenesis of sepsis. Nature. Dec 2002;420(6917): De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. The New England journal of medicine. Apr ;362(9): Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: Critical care medicine. Vol : Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics*. Pediatric Critical Care Medicine. 2005;6(1): Han YY, Carcillo JA, Dragotta MA, et al. Early Reversal of Pediatric-Neonatal Septic Shock by Community Physicians Is Associated With Improved Outcome. PEDIATRICS. Oct ;112(4):

60 AKI & CRRT Jean-Baptiste E. Cellular Mechanisms in Sepsis. Journal of Intensive Care Medicine. Apr ;22(2): Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. The New England journal of medicine. Aug ;345(8): Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock*. Critical Care Medicine. May ;33(4): Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine. Nov ;345(19): Russell JA. Management of sepsis. The New England journal of medicine. Oct ;355(16): Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. The New England journal of medicine. Mar ;358(9): Zeerleder S. Disseminated Intravascular Coagulation in Sepsis. Chest. Oct ;128(4):

61 LUNCH SYMPOSIUM A. New Kids on the Block: Emerging Biomarkers in AKI, CKD and Cardiorenal Syndrome Wednesday, February 17, 11:30-1:00 Marlies Ostermann, MD Educational Objectives: 1. to appreciate the need for novel biomarkers to predict and diagnose AKI 2. to understand the current role of penkid, chitinase 3 like protein and galectin 3 as biomarkers for AKI 3. to appreciate the role of novel biomarkers in the pathophysiology of AKI and its long-term consequences Content Description: AKI affects up to 50% of critically ill patients and is associated with short and long-term complications and increased mortality. Several biomarkers have been identified which predict, diagnose or prognosticate AKI and need for renal replacement therapy. These molecules have improved the diagnosis of AKI and also advanced our understanding of its pathophysiology and potential long-term sequelae. The aim of the symposium is to explore the data of penkid, chitinase 3 like protein and galectin 3 which have emerged as potential biomarkers for AKI. The speakers will review the role of penkid in predicting and diagnosing AKI in sepsis and acute heart disease, summarise the data on chitinase 3 like protein as a marker for diagnosis of AKI in general ICU patients and after renal transplantation and explore the role of galectin 3 in the pathogenesis and prediction of CKD after AKI Suggested Reading: AKI & CRRT 2016 Marino R, Struck J, Hartmann O et al. Diagnostic and short-term prognostic utility of plasma proenkephalin (pro-enk) for acute kidney injury in patients admitted with sepsis in the emergency department. J Nephrol 2015;28(6): Shah KS, Taub P, Patel M et al. Proenkephalin predicts acute kidney injury in cardiac surgery patients. Clin Nephrol 2015;83(1):29-35 Maddens B, Ghesquiere B, Vanholder R et al. Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury. Mol Cell Proteonomics 2012;11(6):M Huen SC, Parikh CR. Molecular phenotyping of clinical AKI with novel urinary biomarkers. Am J Physiol Renal Physiol 2015;309:F O Seaghdha CM, Hwang SJ, Ho JE. Elevated galectin-3 precedes the development of CKD. J Am Soc Nephrol 2013:24: Gopal DM, Kommineni M, Ayalon N et al. Relationship of plasma galectin-3 to renal function in patients with heart failure: effects of clinical status, pathophysiology of heart failure, and presence or absence of heart failure. J Am Heart Assoc 2012; 1:e Varrier M, Forni L, Ostermann M. Long-term sequelae from acute kidney injury: Potential mechanisms for the observed poor renal outcomes. Crit Care 2015;19(1):R102 60

62 AKI & CRRT 2016 Lunch Symposium B. Fluid Management of the Critically Ill Patient: Crystalloids, Colloids and Blood Products Wednesday, February 17, 11:30-1:00 John Prowle MA MSc MD FRCP FFICM Educational Objectives: To understand the indications for and adverse effects of fluid therapy and how the risk/benefit analysis alters during different phase of critical illness. To understand how fluid therapy can have adverse effects on organ function in general and in particular on renal function To understand how fluid administration, fluid balance management and fluid removal can be integrated in a fluid management strategy Content Description: Fluid Management of the Critically Ill Patient: Crystalloids, Colloids and Blood Products This symposium will discuss the pathophysiology for fluid distribution, review recent evidence for the optimal application of different fluids to support ICU patients safely in the ICU This lecture focuses on in indications for fluid administration versus the limiting factors on the effectiveness of fluid therapy and how, in critical illness, the development of fluid overload is an almost inevitable sequelae of resuscitation. Key points: Fluid overload is an almost universal finding in the critically ill, despite little evidence to justify fluid therapy within the intensive care unit after initial resuscitation. Hemodynamic responses to fluid administration are unpredictable and short lived, which may contribute to recurrent fluid administration. Positive fluid balances have been consistently associated with adverse outcomes and organ dysfunction in critical illness. Structural and functional changes in the endothelium and extracellular matrix during systemic inflammation leads to sequestration of administered fluid outside the circulation, promoting fluid accumulation and impeding its removal. Strategies to manage fluid balances in the critically ill require close attention to true need for fluid administration and active prevention or management of fluid overload. Suggested Reading: O'Connor ME, Prowle JR. Fluid Overload. Crit Care Clin Oct;31(4): doi: /j.ccc Rosner MH, Ostermann M, Murugan R, Prowle JR, Ronco C, Kellum JA, Mythen MG, Shaw AD; ADQI XII Investigators Group. Indications and management of mechanical fluid removal in critical illness. Br J Anaesth Nov;113(5): doi: /bja/aeu297 Prowle JR, Kirwan CJ, Bellomo R. Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol Jan;10(1): doi: /nrneph

63 AKI & CRRT 2016 Etiology and Prediction of AKI After Major Trauma Wednesday, February 17, 2:15-2:30 John Prowle MA MSc MD FRCP FFICM Educational Objectives: To review the incidence and associated mortality of AKI after major trauma To discuss the conditions associated with AKI after trauma and potential predictors or severe AKI and death To review the management of Rhabdomyolysis as a specific AKI aetiology Content Description: Approximately 15% of patients admitted to the ICU after major trauma develop AKI within the first week finding that is associated with increased risk of death. While, traditionally, Rhabdomyolysis has been considered the leading cause of traumatic AKI a range of other AKI aetiologies exist in Trauma patients including hypovolaemia, secondary sepsis, systemic inflammatory states, transfusion and nephrotoxins. Management of Rhabdomyolysis has traditionally focused on liberal fluid administration, although the evidence base for this practice is not strong and the author would encourage close monitoring of fluid balance when adopting this approach. The benefit of myoglobin removal using CRRT is even less clear cut and benefit can be difficult to assess as often the overall level of injury determines outcome rather than the presence and treatment of AKI. 62

64 AKI & CRRT 2016 Endothelial Barrier Function is Critical for Renal Recovery Wednesday, February 17, 4:00-4:15 Mark D. Okusa MD Educational Objectives: 1. Describe the critical events that occur during kidney recovery from AKI 2. Describe the role of the endothelium in kidney recovery 3. Describe the role of sphingosine 1-phosphate receptors in kidney recover. Content Description: Cell barriers between different compartments are important in normal physiology. The endothelial cell (EC) barrier separates circulating vascular components from the interstitium, and disruption of the EC barrier results in increased vascular permeability with subsequent inflammation and organ dysfunction1,2; in neoplastic disease this is accompanied by neoangiogenesis and subsequent tumor metastasis. S1P maintains EC barrier integrity primarily by binding to S1P13,4. We used an inducible genetic approach in a mouse model of AKI, ischemia-reperfusion injury (IRI), to determine the temporal effects of endothelial S1P1 during AKI. Deletion of endothelial S1P1 prior to IRI exacerbated kidney injury and inflammation and the delayed deletion of S1P1 after IRI prevented kidney recovery resulting in chronic inflammation and progressive fibrosis. Specifically, S1P1 directly suppressed endothelial activation of leukocyte adhesion molecule expression and inflammation. Altogether, data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery from AKI. Endothelial S1P1 may be a potential therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI. Suggested Reading: 1.Molitoris BA. Therapeutic translation in acute kidney injury: the epithelial/endothelial axis. J Clin Invest 2014;124: Sutton TA, Fisher CJ, Molitoris BA. Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int 2002;62: Singleton PA, Dudek SM, Chiang ET, Garcia JG. Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and alpha-actinin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2005;19: Feistritzer C, Riewald M. Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 2005;105:

65 Lung Transplantation and AKI Wednesday, February 17, 4:15-4:30 Sean Bagshaw MD, MSc, FRCPC AKI & CRRT 2016 Educational Objectives: 1. Describe the epidemiology of AKI associated with lung transplantation 2. Describe the unique peri-operative management challenges after lung transplantation associated with AKI 3. Describe the long-term impact of AKI after lung transplantation for kidney recovery Content Description: Lung transplantation (LTx) has emerged as the preferred treatment modality for patients with a variety of end-stage lung diseases to prolong life expectancy and improve quality of life. Despite significant improvements in both short and long-term mortality, medical complications after LTx contribute to significant morbidity and mortality. Acute kidney injury (AKI) is an serious complication after LTx, occurring in 39-65%, of which 5-13% require renal replacement therapy (RRT). Several studies have described pre-operative susceptibilities for developing AKI after LTx, including older age, worse baseline kidney function, selected etiologies of lung disease, presence of pulmonary hypertension and diabetes mellitus. Fewer studies have examined for intra- and post-operative modifiable risk factors. Pathophysiologic lung-kidney interaction, in particular related to fluid management in the peri-operative setting, can present significant management challenges. Post-operative AKI has been associated with reduced patient and graft survival. In addition, declines in kidney function and new chronic kidney disease (CKD) are increasingly recognized as important sources of long-term morbidity after LTx. This talk will discuss the epidemiology and outcomes associated with AKI after LTx. Suggested Reading: 1. Lyu DM, Zamora MR. Medical complications of lung transplantation. Proceedings of the American Thoracic Society 2009;6: Fidalgo P, Ahmed M, Meyer SR, Lien D, Weinkauf J, Kapasi A, Cardoso FS, Jackson K, Bagshaw SM. Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study. J Crit Care 2014; 29(6): Fidalgo P, Ahmed M, Meyer SR, Lien D, Weinkauf J, Cardoso FS, Jackson K, Bagshaw SM. Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: a population-based cohort study. Nephrol Dial Transplant. 2014;29(9): Rocha PN, Rocha AT, Palmer SM, Davis RD, Smith SR. Acute renal failure after lung transplantation: incidence, predictors and impact on perioperative morbidity and mortality. Am J Transplant 2005;5: Arnaoutakis GJ, George TJ, Robinson CW, et al. Severe acute kidney injury according to the RIFLE (risk, injury, failure, loss, end stage) criteria affects mortality in lung transplantation. J Heart Lung Transplant 2011;30: Wehbe E, Brock R, Budev M, et al. Short-term and long-term outcomes of acute kidney injury after lung transplantation. J Heart Lung Transplant 2012;31: George TJ, Arnaoutakis GJ, Beaty CA, et al. Acute kidney injury increases mortality after lung transplantation. Ann Thorac Surg 2012;94: Hennessy SA, Gillen JR, Hranjec T, et al. Influence of hemodialysis on clinical outcomes after lung transplantation. Journal Surg Res Barraclough K, Menahem SA, Bailey M, Thomson NM. Predictors of decline in renal function after lung transplantation. J Heart Lung Transplant 2006;25: Paradela de la Morena M, De La Torre Bravos M, Prado RF, et al. Chronic kidney disease after lung transplantation: incidence, risk factors, and treatment. Transplantation proceedings 2010;42:

66 AKI & CRRT 2016 Sepsis-associated AKI Has Unique Epidemiology and Molecular Signatures Wednesday, February 17, 4:30-4:45 John A. Kellum MD Educational Objectives: To examine the outcomes associated with sepsis-induced AKI To compare and contrast sepsis from other etiologies of AKI To review molecular biology data in sepsis and non-septic AKI Content Description: Acute kidney injury (AKI) is a common complication in critically ill patients, and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI in the critically ill. Recent evidence points to important differences in the epidemiology of sepsis-induced AKI including differences in the chance and consequences of recovery. Furthermore, considerable evidence has shown that AKI can occur in the absence of overt clinical signs of shock, and in the setting of increased, rather than decreased renal blood flow. This has challenged the traditional paradigm that renal dysfunction is solely on the basis of hypoperfusion and ischemia. Animal and human data have further shown that sepsis-induced AKI is characterized not by acute tubular necrosis, but by a paucity of apoptosis and necrosis in the context of a very bland histology, by inflammation, by microvascular dysfunction, and cellular bioenergetics adaptive responses. These novel findings suggest that other potential mechanisms centered in these three domains may help explain the pathophysiology of sepsis-induced AKI. Furthermore, the extreme functional changes seen in sepsis-induced AKI and the response of the tubular epithelial cells to inflammation and injury may be adaptive. Suggested Reading: 1. Kellum, J. A., Chawla, L. S., Keener, C., Singbartl, K., Palevsky, P. M., Pike, F. L., et al. (2015). The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. American Journal of Respiratory and Critical Care Medicine. 2. Gomez, H., Ince, C., De Backer, D., Pickkers, P., Payen, D., Hotchkiss, J., & Kellum, J. A. (2014). A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock (Augusta, Ga.), 41(1), Kashani, K., Al-Khafaji, A., Ardiles, T., Artigas, A., Bagshaw, S. M., Bell, M., et al. (2013). Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical Care (London, England), 17(1), R25. 65

67 Cardiac Surgery Associated AKI Wednesday, February 17, 4:45-5:00 Xiaoquiang Ding AKI & CRRT 2016 Educational Objectives: 1. Describe the epidemiology of cardiac surgery associated acute kidney injury (CSA-AKI) 2. Describe the social burden of CSA-AKI including short- and long-term burden 3. Discuss the management of CSA-AKI, including nondialytic management, dialytic management and fluid management Content Description: Cardiac surgery associated acute kidney injury (CSA-AKI) is known to be a common complication of cardiac surgery which is associated with poor short- and long-term outcomes. Recognizing and mediating risk factors preoperatively and optimizing intraoperative practices may decrease the incidence of CSA-AKI. The incidence of CSA-AKI and mortality is unlikely to be significantly reduced by any one aspect of management due to its complex pathogenesis. Prevention and interventions of CSA-AKI requires a multimodal approach where both the premorbid condition of the patient and the particular idiosyncrasies of the cardiac surgical procedure itself are taken into account. Timely intervention requires early recognition of potential kidney injury. For now, RRT is the mainstay of supportive treatment for CSA-AKI patients. The prompt, judicious application of RRT is the key to improve outcomes. Potential favorable pharmacologic interventions include natriuretic peptides, such as nesiritide, and use of dopamine agonists, such as fenoldopam may also help. Suggested Reading: 1.Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Inter. 2012;2(Suppl): Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009;119(4): R. BELLOMO, S. AURIEMMA, A. FABBRI, et al.the pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI).The International Journal of Artificial Organs.31(2): Bellomo R, Cass A, Cole L, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17): Jiarui Xu, Xiaoqiang Ding, Yi Fang, et al. New, goal-directed approach to renal replacement therapy improves acute kidney injury treatment after cardiac surgery. J Cardiothorac Surg. 2014, 9:103 6.Prowle JR, Chua HR, Bagshaw SM, et al. Clinical review: volume of fluid resuscitation and the incidence of acute kidney injury a systematic review. Crit Care. 2012;16:

68 A15 Optimal Care for AKI: The 5 R Approach Thursday, February 18, 8:00-9:30 Jorge Cerda MD, FACP, FASN AKI & CRRT 2016 Educational Objectives: At the completion of the workshop, attendees will be able to: 1. Describe the most recent findings on the epidemiology of AKI 2. Summarize the personal, societal and economic impact of AKI around the world 3. Describe examples of practical initiatives in high income and low and middle income countries in pediatric and adult populations, designed to promote early recognition and management of AKI 4. Implement initiatives to raise awareness of AKI and to promote early management of the problem Content Description: Worldwide, AKI is associated with poor patient outcomes. Over the last few years, collaborative efforts, enabled by a common definition of AKI, have provided an improved description of the epidemiology, natural history, and outcomes of disease. There is increased recognition that AKI is encountered in multiple settings and all age groups, and that its course and outcomes are influenced by the severity and duration of the event. The effect of AKI on an individual patient and the resulting societal burden ensuing form the long term effect of the disease including development of CKD and ESRD are increasingly clear. Marked variation in the management of AKI, in large part due to a lack of awareness or absence of standards for prevention, early recognition and intervention, lead to worse outcomes. Emerging data indicate a need for a global effort to highlight that AKI is preventable, its course modifiable and its treatment can improve outcomes. Early Risk assessment, Recognition, Response, Renal support and Rehabilitation (The - R Aproach) will help decrease the incidence and improve outcomes around the world. In this workshop, we will briefly describe the status of AKI epidemiology, its impact on patient outcomes and how special populations are affected. We will describe the development of initiatives to raise awareness and promote education on AKI in the UK, and demonstrate the actual implementation of such initiatives in Tanzania. The workshop will illustrate how new initiatives will likely lead to earlier recognition, better management and more favorable patient outcomes in different contexts around the world. Suggested Reading: Lewington AJ, Cerdá, J, Mehta RL: Raising awareness of acute kidney injury: A global perspective of a silent killer. Kidney Int, 2013; 84(3): Cerdá J, Bagga A, Kher V, Chakravarthi RM. The contrasting characteristics of acute kidney injury in developed and developing countries. Nature Clin Pract Nephrol. 2008;4(3): Susantitaphong P, Cruz DN, Cerdá, J, Abulfaraj M, Alqahtani F, Koulouridis I, Goldstein SL, Jaber S for the Acute Kidney Injury Advisory Group of the American Society of Nephrology. Worldwide Incidence of Acute Kidney Injury: A Meta-analysis. Clin J Am Soc Nephrology, 2013; 8(9): Ravindra L Mehta, MD*, Jorge Cerdá*, Emmanuel A. Burdmann *, Marcello Tonelli*, Guillermo García-García, Vivekanand Jha Paweena Susantitaphong, Michael Rocco Raymond Vanholder, Mehmet Sukru Sever, Dinna Cruz, Bertrand Jaber, Norbert H Lameire, Raúl Lombardi, Andrew Lewington, 67

69 AKI & CRRT 2016 John Feehally MD, Fredric Finkelstein, Nathan Levin, Neesh Pannu, Bernadette Thomas, Eliah Aronoff-Spencer and Giuseppe Remuzzi. (*Joint first authors). International Society of Nephrology s 0by25 for acute kidney injury: a human rights case for nephrology. The Lancet 2015 Jun 27;385(9987): Mehta RL, A. Burdmann EA, Cerdá J, Feehally J, Finkelstein F, García-García G, Godin M, Jha V, Lameire N, Levin N, Lewington A, Lombardi R, Macedo E, Rocco M, Aronoff-Spencer E, Tonelli M, Zhang J, Remuzzi G Current Practice for Recognition and Management of Acute Kidney Injury: the ISN 0by25 Global Snapshot Study. Accepted for publication, The Lancet, 2015 Josée Bouchard, Anjali Acharya, Jorge Cerdá, Elizabeth R. Maccariello, Rajasekara Chakravarthi Madarasu, Ashita J. Tolwani, Xinling Liang, Ping Fu, Zhi-Hong Liu and Ravindra L. Mehta. Acute kidney injury in the intensive care unit: A prospective international multicenter study. CJASN 2015;10(10): Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol 2010;5(5):943-9 Goldstein SL, Kirkendall E, Nguyen H et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Pediatrics 2013 Moffett BS, Goldstein SL. Acute kidney injury and increasing nephrotoxic medication exposure in noncritically-ill children. Clin J Am Soc Nephrol 2011;6: Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary care center from 1999 to Am J Kidney Dis 45: Hsu RK, McCulloch CE, Dudley RA et al. Temporal changes in incidence of dialysis requiring AKI. J Am Soc Nephrol 2013;24(1):37-42 NECPOD. The National Confidential Enquiry into Patient Outcome and Death clinical quest.pdf 68

70 AKI & CRRT 2016 B16 CRRT for the Experienced User 2: Solutions, Fluid Removal Fluid Balance, Monitoring Thursday, February 18, 8:00-9:30 John Prowle MA MSc MD FRCP FFICM Educational Objectives: To understand the indications for and monitoring of fluid removal during CRRT To understand the reasoning behind the composition of CRRT replacement/dialysis fluids To understand the role of CRRT in the management of major acid-base, solute and electrolyte disorders Content Description: Using a case-based approach the presenters will consider how CRRT treatment can be tailored to safely and effectively mange critically ill patients with major fluid, acid-base and electrolyte disorders occurring in conjunction with severe acute kidney injury. 69

71 B16 CRRT for the Experienced User 2: Solutions, Fluid Removal Fluid Balance, Monitoring Thursday, February 18, 8:00-9:30 Ravindra L. Mehta, MBBS, MD, DM, FACP Educational Objectives: 1. Describe the goals of fluid management in critically ill patients and identify complications of fluid resuscitation. 2. Discuss the principles of fluid management with CRRT techniques and discuss the practical issues in developing a strategy for using CRRT as a fluid regulatory device. 3. Describe the practical issues related to fluid regulation with CRRT based on different modalities and pumps. Content Description: Volume support is frequently required in critically ill patients exhibiting hypovolemia particularly in the setting of shock, systemic inflammatory response syndrome (SIRS) and sepsis. Often volume management results in a fluid overloaded state requiring diuresis or dialytic intervention. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, selection of an appropriate solution for volume repletion and maintenance and modulation of the tissue perfusion and cellular injury. In the presence of a failing kidney, fluid removal is often a challenge and it is often necessary in this setting to institute dialysis for volume control rather than metabolic control. CRRT techniques offer a significant advantage over intermittent dialysis for fluid control, however, if not carried out appropriately it can result in major complications. In order to utilize these therapies for their maximum potential it is necessary to recognize the factors which influence fluid balance and have an understanding of the principles of fluid management with these techniques. This workshop will describe the current concepts of volume management in shock states and discuss the basic methods for fluid management with CRRT and provide an approach to targeted intervention in critically ill patients. We will use case studies to describe various approaches for fluid removal and regulation with CRRT. Presentation Outline: AKI & CRRT Assessment of Volume Status Components (Space, amount, content); Clinical evaluation; Monitoring 2. Goals of Fluid Management Permit fluid resuscitation without overload; Fluid removal; Establish fluid balance; Maintain urine output 3. Review of Principles of Fluid Management with CRRT Role of fluids in CRRT; Components of fluid management; Ultrafiltrate; Replacement fluid and dialysate; Systems for Fluid balance 4. Approaches to fluid management Fluid removal vs Fluid Regulation Strategy; Levels of intervention; Advantages and disadvantages 5. Practical Issues Prescription; Implementation; Achieving fluid balance with different pumped systems; Monitoring and Charting 6. Complications 70

72 Types, Prevention, Management 8. Continuous Quality Improvement Protocol based management; Computer support AKI & CRRT 2016 Suggested Reading: [1-17] [4-6, 11, 18-37] 1. Bagshaw SM, Baldwin I, Fealy N, Bellomo R: Fluid balance error in continuous renal replacement therapy: a technical note. Int J Artif Organs 2007, 30(5): Bagshaw SM, Brophy PD, Cruz D, Ronco C: Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury. Crit Care 2008, 12(4): Bellomo R: Bench-to-bedside review: lactate and the kidney. Crit Care 2002, 6(4): Bouchard J, Mehta RL: Fluid accumulation and acute kidney injury: consequence or cause. Curr Opin Crit Care 2009, 15(6): Bouchard J, Mehta RL: Volume management in continuous renal replacement therapy. Semin Dial 2009, 22(2): Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL: Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009, 76(4): Gibney N, Cerda J, Davenport A, Ramirez J, Singbartl K, Leblanc M, Ronco C: Volume management by renal replacement therapy in acute kidney injury. Int J Artif Organs 2008, 31(2): Jabara AE, Mehta RL: Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 1995, 41(3):M Mehta RL: Fluid management in CRRT. Contrib Nephrol 2001(132): Mehta RL: Fluid balance and acute kidney injury: the missing link for predicting adverse outcomes? Nat Clin Pract Nephrol 2009, 5(1): Mehta RL, Cantarovich F, Shaw A, Hoste E, Murray P: Pharmacologic approaches for volume excess in acute kidney injury (AKI). Int J Artif Organs 2008, 31(2): Mehta RL, Clark WC, Schetz M: Techniques for assessing and achieving fluid balance in acute renal failure. Curr Opin Crit Care 2002, 8(6): Murugan R, Venkataraman R, Wahed AS, Elder M, Carter M, Madden NJ, Kellum JA: Preload responsiveness is associated with increased interleukin-6 and lower organ yield from brain-dead donors. Crit Care Med 2009, 37(8): Naka T, Bellomo R, Morimatsu H, Rocktaschel J, Wan L, Gow P, Angus P: Acid-base balance during continuous veno-venous hemofiltration: the impact of severe hepatic failure. Int J Artif Organs 2006, 29(7): Ronco C: Fluid balance in CRRT: a call to attention! Int J Artif Organs 2005, 28(8): Ronco C, Ricci Z, Bellomo R, Baldwin I, Kellum J: Management of fluid balance in CRRT: a technical approach. Int J Artif Organs 2005, 28(8): Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM et al: Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis, 55(2): Bouchard J, Mehta RL: Acid-base disturbances in the intensive care unit: current issues and the use of continuous renal replacement therapy as a customized treatment tool. Int J Artif Organs 2008, 31(1): Cerda J, Sheinfeld G, Ronco C: Fluid overload in critically ill patients with acute kidney injury. Blood Purif, 29(4):

73 AKI & CRRT Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R: Fluid balance and acute kidney injury. Nat Rev Nephrol, 6(2): Prowle J, Bellomo R, Buckmaster J, Gutteridge G, Hart G, Opdam H, Silvester W, Warrillow S: Continuous hemofiltration for anasarca: recovery of renal function after 71 liters of net ultrafiltration. Int J Artif Organs 2008, 31(4): Kugener L, Brasseur A, Fagnoul D, Vincent JL: High rate ultrafiltration in anasarca: 33 l of net negative fluid balance in 52 h! Intensive Care Med, 37(1): Mehta RL, Bouchard J: Controversies in acute kidney injury: effects of fluid overload on outcome. Contrib Nephrol 2011, 174: Liu KD, Thompson BT, Ancukiewicz M, Steingrub JS, Douglas IS, Matthay MA, Wright P, Peterson MW, Rock P, Hyzy RC et al: Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes. Critical care medicine 2011, 39(12): Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD: Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 2011, 6(5): Claure-Del Granado R, Mehta RL: Assessing and delivering dialysis dose in acute kidney injury. Semin Dial 2011, 24(2): Yerram P, Karuparthi PR, Misra M: Fluid overload and acute kidney injury. Hemodial Int 2010, 14(4): Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM et al: Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 2010, 55(2): Schrier RW: Fluid administration in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2010, 5(4): Rewa O, Bagshaw SM: Principles of Fluid Management. Crit Care Clin 2015, 31(4): Prowle JR, Kirwan CJ, Bellomo R: Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol 2014, 10(1): Martin GS: State-of-the-art fluid management in critically ill patients. Curr Opin Crit Care 2014, 20(4): Hoste EA, Maitland K, Brudney CS, Mehta R, Vincent JL, Yates D, Kellum JA, Mythen MG, Shaw AD, Group AXI: Four phases of intravenous fluid therapy: a conceptual model. Br J Anaesth 2014, 113(5): Ronco C, Ricci Z, De Backer D, Kellum JA, Taccone FS, Joannidis M, Pickkers P, Cantaluppi V, Turani F, Saudan P et al: Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care 2015, 19: Acheampong A, Vincent JL: A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015, 19: Mariscalco G, Musumeci F: Fluid management in the cardiothoracic intensive care unit: diuresis- -diuretics and hemofiltration. Curr Opin Anaesthesiol 2014, 27(2): O'Connor ME, Prowle JR: Fluid Overload. Crit Care Clin 2015, 31(4):

74 AKI & CRRT 2016 F20 Pediatric Dialysis Techniques 2: CRRT in the Newborn, ECMO, Combination Therapies, Drug Dosing, Transitions Thursday, February 18, 8:00-9:30 David Askenazi MD, MSPH Educational Objectives: 1. Describe the epidemiology of acute kidney injury in neonates, including the outcomes of small children who receive CRRT. 2. Understand the special technical considerations associated with performing neonatal CRRT 3. Understand the general indications for neonatal CRRT, with a special focus on inborn errors of metabolism 4. Discuss new technology for neonatal CRRT. Content Description: For many years any form of dialysis support was considered too difficult for neonates; for those centers that would provide renal replacement, peritoneal dialysis was considered the only viable modality. Over the past few decades, however, the use of CRRT in the neonatal intensive care unit has expanded substantially. Performing CRRT for newborn patients presents unique challenges. There are significant technical barriers to performing CRRT in neonates and risks may be magnified when devices and materials designed for use in adults are adapted to the care of very small patients. This session will discuss the epidemiology of acute kidney injury in the newborn, demographics and outcomes in neonates receiving CRRT, indications for CRRT including its use in the management of inborn errors of metabolism, and technical approaches to the procedure with emphasis on the differences from therapy as used in older children and adults. In addition, we will discuss new technologies designed specifically for the care of the neonate who requires CRRT. We look forward to an interactive session where members of the audience will share their own experiences, allowing all participants to gain further knowledge1. Suggested Reading: 1. Askenazi DJ, et. al.. Continuous Renal Replacement Therapy for Children 10 kg: A Report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry. J Pediatr Oct Symons JM et al. Continuous renal replacement therapy in children up to 10 kg. Am J Kid Dis (2003) 18: Askenazi DJ et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr (2011) 159: Askenazi DJ et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med (2011) 12:e1-e6. 5. Brophy PD et al. AN-69 membrane reactions are ph-dependent and preventable. Am J Kid Dis (2001) 38: Hackbarth RM, et. al.. Zero balance ultrafiltration in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection. Pediatr Nephrol Sep;20(9): McBryde KD et al. Renal replacement therapy in the treatment of confirmed or suspected inborn 73

75 AKI & CRRT 2016 errors of metabolism. J Pediatr (2006) 8. Pasko DA et al. Pre dialysis of blood prime in continuous hemodialysis normalizes ph and electrolytes. Pediatr Nephrol (2003) 18: Picca S et al. Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators. Pediatr Nephrol (2001) 16: Schaefer F et al. Dialysis in neonates with inborn errors of metabolism. Nephrol Dial Transplant (1999) 14: Askenazi D, Ingram D, White S, et al. Smaller circuits for smaller patients: improving renal support therapy with Aquadex. Pediatric nephrology (Berlin, Germany)

76 AKI & CRRT 2016 Diagnostic and Therapeutic Potential of Microevsicles in AKI Thursday, February 18, 10:30-10:45 Vincenzo Cantaluppi MD Educational Objectives: 1. Definition, classification and potential biological role of microvesicles (MV) in acute kidney injury and organ cross-talk in physiologic and pathologic states. 2. Discuss the role of MV as early and accurate biomarkers and mediators of AKI in different conditions: a) sepsis-associated AKI; b) acute impairment of kidney graft function. 3. Discuss the potential role of MV released from bone marrow-derived stem cells as paracrine factors involved in tissue regeneration following AKI. Content Description: Microvesicles (MV) represent a new concept of intercellular cross-talk. MV are small particles released by different types of activated cells through a membrane sorting process. MV are able to modulate the biological behaviour of neighbouring cells through the transfer of specific receptors, proteins, bioactive lipids, organelles and in particular genetic material. Indeed, MV are particularly enriched for mrna and microrna that can be horizontally transferred to target cells inducing their epigenetic reprogramming. We herein discuss the potential role of MV as early and accurate biomarkers and mediators of AKI in 2 different settings: 1) plasma MV in sepsis-associated AKI; 2) urine MV in acute loss of function of kidney transplanted patients. A particular focus will be dedicated to the modulation of mrna and microrna content of MV in the course of AKI. Last, we discuss the potential therapeutic application of MV released from stem cells (bone marrow-derived mesenchymal stem cells and endothelial progenitor cells) in tissue regeneration after AKI due to ischemia-reperfusion injury and sepsis. Suggested Reading: 1: Humphreys BD, Cantaluppi V, Portilla D, Singbartl K, Yang L, Rosner MH, Kellum JA, Ronco C; Acute Dialysis Quality Initiative (ADQI) XIII Work Group. Targeting Endogenous Repair Pathways after AKI. J Am Soc Nephrol Nov 18. pii: ASN [Epub ahead of print] PubMed PMID: : Cantaluppi V, Medica D, Mannari C, Stiaccini G, Figliolini F, Dellepiane S, Quercia AD, Migliori M, Panichi V, Giovannini L, Bruno S, Tetta C, Biancone L, Camussi G. Endothelial progenitor cell-derived extracellular vesicles protect from complement-mediated mesangial injury in experimental anti-thy1.1 glomerulonephritis. Nephrol Dial Transplant Mar;30(3): doi: /ndt/gfu364. Epub 2014 Dec 8. PubMed PMID: : Camussi G, Deregibus MC, Cantaluppi V. Role of stem-cell-derived microvesicles in the paracrine action of stem cells. Biochem Soc Trans Feb 1;41(1):283-7.doi: /BST Review. PubMed PMID: : Cantaluppi V, Biancone L, Quercia A, Deregibus MC, Segoloni G, Camussi G. Rationale of mesenchymal stem cell therapy in kidney injury. Am J Kidney Dis. 75

77 AKI & CRRT Feb;61(2): doi: /j.ajkd Epub 2012 Aug 30. PubMed PMID: : Cantaluppi V, Gatti S, Medica D, Figliolini F, Bruno S, Deregibus MC, Sordi A, Biancone L, Tetta C, Camussi G. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemiareperfusion injury by microrna-dependentreprogramming of resident renal cells. Kidney Int Aug;82(4): doi: /ki Epub 2012 Apr 11. PubMed PMID: : Bruno S, Grange C, Collino F, Deregibus MC, Cantaluppi V, Biancone L, Tetta C,Camussi G. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One. 2012;7(3):e doi: /journal.pone Epub 2012 Mar 14. PubMed PMID: ; PubMed Central PMCID: PMC : Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, Camussi G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant May;26(5): doi: /ndt/gfr015. Epub 2011 Feb 15. PubMed PMID: : Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int Nov;78(9): doi: /ki Epub 2010 Aug 11. Review. PubMed PMID: : Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontaltransfer of mrna. Blood Oct 1;110(7): Epub 2007 May 29. PubMed PMID:

78 AKI & CRRT 2016 Lunch Symposium D. Injury Matters: The Role of Risk Assessment and Early Intervention in AKI Thursday, February 18, 12:15-1:45 Jay Koyner MD Educational Objectives: please limit to 3 objectives 1) Identify studies which harness the power of the electronic medical record to improve AKI risk assessment and patient outcomes 2) To understand how biomarkers and risk schema can be used to improve AKI risk assessment prior to the development of AKI i.e. optimize pre-test probability 3) To understand how biomarkers (functional and injury) can be used to improve AKI risk assessment 4) To summarize the recent literature on successful early interventions in the setting of AKI Content Description: This session will focus on the multiple improvements that have been made in AKI risk stratification over the last several years. We will start by highlighting the emerging capabilities of the electronic health record in improving the identification and care of patients with AKI and at high risk for AKI. We will discuss the idea of electronic sniffers, alerts, and studies such as the Nephrotoxic Injury Negated by Justin-Time Action (NINJA) study. All of which have either demonstrated clinical feasibility or improvements in processes of care or patient outcomes. Next we will discuss developments in the earlier recognition of AKI. This has been done through the use of newer biomarkers but also through improved risk assessment tools such as renal angina index. The use of these new tools and their ability to optimize pre-test probability (before creatinine or urine output based AKI has developed) will be discussed in a case based fashion. We will further discuss how many of these same biomarkers and other functional assessments, like the furosemide stress test can improve the discrimination of those who are destined for adverse events (e.g. need for RRT, inpatient mortality) in the setting of early AKI. Clinical scenarios will be discussed to demonstrate how these tests optimize the post-test probability and how they can be used to enhance patient selection for AKI clinical trials. Finally, throughout the session, we will be discussing a variety of interventions that have been demonstrated to decrease AKI event rates or improve its outcomes (e.g. electronic alerts, remote ischemic preconditioning). Suggested Reading: 1) Pediatrics Sep;132(3):e Epub 2013 Aug 12. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Goldstein SL1, Kirkendall E, Nguyen H, Schaffzin JK, Bucuvalas J, Bracke T, Seid M, Ashby M, Foertmeyer N, Brunner L, Lesko A, Barclay C, Lannon C, Muething S. 2) Clin J Am Soc Nephrol Apr;9(4): Epub 2014 Mar 27. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Basu RK1, Wang Y, Wong HR, Chawla LS, Wheeler DS, Goldstein SL. 77

79 AKI & CRRT ) Kidney Int Mar;85(3): Epub 2013 Sep 18. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Basu RK1, Zappitelli M2, Brunner L3, Wang Y4, Wong HR5, Chawla LS6, Wheeler DS1, Goldstein SL7. 4) J Crit Care May 19. pii: S (15) [Epub ahead of print] Development and validation of electronic surveillance tool for acute kidney injury: A retrospective analysis. Ahmed A1, Vairavan S2, Akhoundi A3, Wilson G4, Chiofolo C2, Chbat N2, Cartin-Ceba R4, Li G4, Kashani K5. 5) Nephron. 2015;131(2):92-6. Epub 2015 Sep 30. Utilities of Electronic Medical Records to Improve Quality of Care for Acute Kidney Injury: Past, Present, Future. Kashani K1, Herasevich V. 6) J Am Soc Nephrol Aug;26(8): Epub 2015 Feb 5. Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity. Koyner JL1, Davison DL2, Brasha-Mitchell E2, Chalikonda DM2, Arthur JM3, Shaw AD4, Tumlin JA5, Trevino SA1, Bennett MR6, Kimmel PL7, Seneff MG2, Chawla LS8. 7) J Am Soc Nephrol May;23(5): Epub 2012 Mar 1. Biomarkers predict progression of acute kidney injury after cardiac surgery. Koyner JL1, Garg AX, Coca SG, Sint K, Thiessen-Philbrook H, Patel UD, Shlipak MG, Parikh CR; TRIBE-AKI Consortium. 8) Hepatology Aug;60(2): Epub 2014 Jun 26. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Belcher JM1, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, Ansari N, Coca SG, Garcia-Tsao G, Parikh CR; TRIBE-AKI Consortium. 9) JAMA Jun 2;313(21): Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. Zarbock A1, Schmidt C1, Van Aken H1, Wempe C1, Martens S2, Zahn PK3, Wolf B3, Goebel U4, Schwer CI4, Rosenberger P5, Haeberle H5, Görlich D6, Kellum JA7, Meersch M1; RenalRIPC Investigators. 10) Lancet May 16;385(9981): Epub 2015 Feb 26. Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial. Wilson FP1, Shashaty M2, Testani J3, Aqeel I4, Borovskiy Y5, Ellenberg SS6, Feldman HI7, Fernandez H8, Gitelman Y5, Lin J5, Negoianu D5, Parikh CR3, Reese PP2, Urbani R9, Fuchs B5. 78

80 AKI & CRRT 2016 Lunch Symposium E. Improving Outcomes in AKI and CRRT: Does Quality Matter? Thursday, February 18, 12:15-1:45 Sean Bagshaw MD, MSc, FRCPC Educational Objectives: 1. Describe the evolution of quality and safety in health care 2. Describe the quality and safety of care provided to patients at risk of or with AKI 3. Describe the quality and safety of care provided to patients receiving acute RRT Content Description: Acute kidney injury (AKI) is common, increasingly encountered and imposes a high short and long-term risk for major morbidity, including incident chronic kidney disease and accelerated progression to endstage kidney disease, and mortality. Patients suffering an episode of AKI consume greater health resources and incur high health care costs, incurred largely from heightened monitoring, more investigations, greater intensity of support and longer durations of hospitalization. Unfortunately, the care of hospitalized patients with AKI has been shown to be susceptible to wide variability in practice. Such practice variation likely stems from a number of sources including the significant heterogeneity in patient populations susceptible to AKI, the range in multi-disciplinary providers who care for patients with AKI, the uncertainty in the evidence-base for the optimal care of patients with AKI, and the incomplete implementation and practical awareness of current best practice guidelines (i.e., Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for AKI). Undoubtedly, these factors have contributed to the inconsistent and suboptimal quality of care for patients with AKI. Indeed, numerous studies have shown the quality of care provided to AKI patients, in terms of risk identification, diagnosis, monitoring, investigations and interventions are clearly suboptimal. These data indicate there are widespread gaps in the recognition, care processes and overall quality of care received by hospitalized patients with AKI. Moreover, these data also imply a meaningful proportion of the major morbidity and mortality associated with AKI may be iatrogenic and attributable to poor quality of care. Yet, in selected circumstances, it is well recognized that AKI can be prevented or the burden reduced with appropriate awareness and tools for early risk identification and diagnosis. This workshop will explore the evolution of quality and safety culture in medicine in general, followed more specifically in the context of AKI and RRT. Suggested Reading: 1. Hsu RK, McCulloch CE, Ku E, Dudley RA, Hsu CY. Regional variation in the incidence of dialysisrequiring AKI in the United States. Clinical Journal of the American Society of Nephrology. 2013;8(9): Aitken E, Carruthers C, Gall L, Kerr L, Geddes C, Kingsmore D. Acute kidney injury: outcomes and quality of care. QJM. 2013;106(4): KDIGO AKI Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;Suppl ((Suppl) 2): Goldstein SL, Kirkendall E, Nguyen H, Schaffzin JK, Bucuvalas J, Bracke T, et al. Electronic health record identification of nephrotoxin exposure and associated acute kidney injury. Pediatrics. 2013;132(3):e National Confidential Enquiry into Patient Outcome and Death (NCEPOD). Adding Insult to Injury: A review of the care of patients who died in hospital with a primary diagnosis of acute kidney injury (acute renal failure) [cited 2015 March 27, 2015]. Available from: 79

81 AKI & CRRT Hoste EA, De Corte W. Implementing the Kidney Disease: Improving Global Outcomes/acute kidney injury guidelines in ICU patients. Current Opinion in Critical Care. 2013;19(6): Resar R, Griffin FA, Haraden C, Nolan TW. Using Care Bundles to Improve Health Care Quality. IHI Innovation Series White Paper. Cambridge, Massachusetts: Institute for Healthcare Improvement 2012 [cited 2015 March 27, 2015]. Available from: 8. National Institutes for Health and Care Exellence (NICE). Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy: National Institutes for Health and Care Exellence (NICE); 2013 [cited 2015 March 27, 2015]. Available from: 9. Tsui A, Rajani C, Doshi R, De Wolff J, Tennant R, Duncan N, et al. Improving recognition and management of acute kidney injury. Acute Medicine. 2014;13(3):

82 AKI & CRRT 2016 Lunch Symposium E. Improving Outcomes in AKI and CRRT: Does Quality Matter? Thursday, February 18, 12:15-1:45 Ian Baldwin RN, PhD, FACCCN Educational Objectives: 1.To review a definition and normal range for filter life associated with CRRT. 2.Identify some key non anticoagulation factors that promote filter life and prevent premature clotting. 3.Review the importance and utility of monitoring filter life as a daily routine when CRRT is in use. Content Description: Although prescribed as continuous, circuit function time is variable in the ICU setting. Data from randomized controlled CRRT trials indicate that approximately 21 hrs is the median time for continuous function before clotting. Prolonging the extracorporeal circuit (EC) can be achieved using anticoagulants such as heparin or citrate. These methods can be effective, however there is great variation in data from single center reports. A protocol with one preferred method, an alternative, and importantly when no anticoagulation applies is a necessary document in any CRRT program. When anticoagulants are not used, or clotting occurs within a few hours despite anticoagulation, blood flow failure and mechanical flow factors within the CRRT circuit should be considered. These factors may include; large Fg access catheter with side-byside lumen profile, femoral vein site selection, pre and post membrane substitution fluids administration, bubble trap blood inlet design, reliable blood pump flow, staff training and troubleshooting ability. An audit routine to quickly know circuit life in your ICU is the final key suggestion. Suggested Reading: 1.Baldwin I, Fealy N, Carty P, Boyle M, Inbyung K, Bellomo R Bubble trap chamber clotting during continuous renal replacement therapy: Vertical versus horizontal blood flow entry. Blood Purification.; 34: Dunn W and Sriram S Filter lifespan in critically ill adults receiving continuous renal replacement therapy: the effect of patient and treatment related variables. Critical Care and Resuscitation. Vol. 16 No. 3. September Boyle M and Baldwin I Understanding the Continuous Renal Replacement Therapy circuit for Acute Renal failure support; A quality issue in the Intensive Care Unit. AACN Advanced Critical Care Vol. 21 No. 4 pp In Byung Kim, Fealy N, Baldwin I, Bellomo R Premature circuit clotting due to likely mechanical failure during Continuous Renal Replacement Therapy. Blood Purification. 30: Oleska R, Mottes T and Bagshaw S M Quality measures for acute kidney injry and continuius renal repalcement therpay. Current Opinion in Critical Care. Vol. 21. No. 6. Dec. Pp Baldwin I Factors affecting circuit patency and filter life. In Contributions to Nephrology Vol pp C Ronco, R Bellomo, J Kellum editors. Basel, Karger. 7.Baldwin I and Bellomo R The relationship between blood flow, access catheter and circuit failure during CRRT; a practical review. Contributions to Nephrology; vol pp Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R Pre-dilution vs. post-dilution during continuous veno-venous hemofiltration: impact on filter life and azotemic control,. Nephron Clinical Practice; 94:4 pp Davies H. and Leslie G Maintaining CRRT circuit: non-anticoagulant alternatives. Australian Critical Care; 19 (4):

83 AKI & CRRT 2016 Lunch Symposium F. Winning The War Against Critical Illness: Role of Post-ICU Quality of Life Thursday, February 18, 12:15-1:45 Noel Gibney MB FRCP(C) Educational Objectives: 1. Draw attention to the importance of Post Intensive Care Syndrome (PICS) 2. Explain the pathogenesis and clinical features of PICS 3. Discuss the prevention and management of PICS Content Description: Winning The War Against Critical Illness: Role of Post-ICU Quality of Life Advances in critical care have resulted in significant improvements in the care of the critically ill. In turn, this has increased the numbers of patients who are surviving critical illness. However, many of these survivors are left with serious consequences. Post-intensive care syndrome, or PICS, consists of health problems that remain after critical illness. It is now recognized that 50-70% of ICU survivors will suffer cognitive impairment and 60-80% will suffer functional impairment or ICU acquired weakness and has led some to question whether we are creating survivors or victims! The consequences include physical, neuropsychiatric and quality of life impairment which may last for many years. Examples of physical limitations include profound weakness, compression neuropathy, impairment of lung function in patients with ARDS and chronic kidney disease in patients with acute kidney injury. Patients and families may also suffer from psychiatric problems including anxiety, depression and posttraumatic stress disorder. In addition, patients may show signs of cognitive impairment with attention problems, lower intelligence and poor or delusional memory. The combination of these physical, psychiatric and cognitive consequences result in a reduced quality of life. In addition, 50% patients are unable to return to work in the first year and 30% never work again. There are a number of measures which can reduce the incidence and severity of PICS including minimizing sedation, particularly with benzodiazepines which predispose to delirium, early mobilization, early and adequate nutrition, use of patient diaries and post-icu follow-up in hospital and in post-icu clinics. Suggested Reading: Davidson JE, Jones C, Bienvenu OJ. Family response to critical illness: postintensive care syndrome. Crit Care Med. 2012;40(2): Desai SV, Law TJ, Needham DM. Long-term complications of critical care. Crit Care Med. 2011;39(2): Griffiths RD, Jones C. The intensive care unit diary and post traumatic stress disorder. Crit Care Med. 2009;37(6): Jones C, Backman C, Capuzzo M, et al. In- tensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial. Crit Care. 2010;14(5):R168. Herridge MS, Cheung AM, Tansey CM, et al: One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348: Intensive care unit-acquired weakness: Pro- ceedings of a Round Table Conference in Brussels, Belgium, March 2009: Crit Care Med 2009; 37(Suppl 10):S295 S461. Schweickert WD, Pohlman MC, Pohlman AS, et al: Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009; 373:

84 AKI & CRRT 2016 DEBATE - Timing of RRT in AKI Thursday, February 18, 5:15-5:45 Early may not be better: Schetz Early is what's needed : Palevsky Miet Schetz MD, PhD Educational Objectives: 1.to discuss the dangers of unnecessary hemodialysis 2.to illustrate the absence of hard evidence for a beneficial effect of early RRT Content Description: The optimal timing of RRT in patients with AKI remains a matter of debate. The decision should weigh the danger of unnecessary RRT versus the danger of delaying RRT in patients that will need it. Our ability to accurately distinguish these two groups of patients is poor. Observational trials comparing early and late start have a high risk of bias and the limited evidence from the available RCT s is not in favor of an early start. Fluid overload at dialysis initiation is associated with worse outcomes but no trial has shown that prevention or reversal of fluid overload with RRT improves outcome. Our expectations towards the currently available RRT s might be too high. Suggested Reading: 1.Schetz M, Forni L, Joannidis M. Does this patient with AKI need RRT?. Intensive Care Medicine 2016; on-line. 2.Clark EG, Bagshaw SM. Unnecessary renal replacement therapy for acute kidney injury is harmful for renal recovery. Semin Dial 2015; 28: Libório AB, Leite TT, Neves FM, Teles F, Bezerra CT (2015) AKI complications in critically ill patients: association with mortality rates and RRT. Clin J Am Soc Nephrol 10: Wald R, Adhikari NK, Smith OM, Weir MA, Pope K, Cohen A, Thorpe K, McIntyre L, Lamontagne F, Soth M, Herridge M, Lapinsky S, Clark E, Garg AX, Hiremath S, Klein D, Mazer CD, Richardson RM, Wilcox ME, Friedrich JO, Burns KE, Bagshaw SM. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int 2015; 88:

85 The Changing Face of AKI in China Friday, February 19, 8:30-8:45 Li Yang MD AKI & CRRT 2016 Educational Objectives: 1. Describe the current disease burden of AKI in China. 2. Discuss the challenge of recognition, diagnosis and treatment of AKI in China. 3. Describe the practical issues brought up to improving the management of AKI in China. Content Description: Acute kidney injury (AKI) has become a worldwide public health problem. During the last two years, several epidemiological studies have been developed to describe the disease burden, clinical features, and current status of diagnosis and treatment of AKI in China. It is estimated that about 3 million cases of AKI are hospitalized in China within a year, causing 700,000 deaths. About 30-40% of AKI cases are drug-related, and herbal medicine remains an important class of drugs inducing AKI in China. There is an inconceivable under diagnosis and under treatment across the country, and delayed AKI recognition was an independent risk factor for in-hospital mortality, while renal referral was an independent protective factor for under recognition and mortality of AKI. This presentation will also introduce ongoing approaches to improve the management of AKI in China. Suggested Reading: 1. Yang L, Xing G, Wang L et al. Acute kidney injury in China: a cross-sectional survey. Lancet 86 (10002): , Xu X, Nie S, Liu Z, Chen C, Xu G, Zha Y, Qian J, Liu B, Han S, Xu A, Xu X, Hou FF. Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults. Clin J Am Soc Nephrol. 10(9): , Wang N, Jiang L, Zhu B, Wen Y, Xi XM; Beijing Acute Kidney Injury Trial (BAKIT) Workgroup. Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study. Crit Care. 19:371, Liu BC, Tang RN, Liu ZH. Current clinical research of acute kidney injury in China. Chin Med J (Engl) 128(9):

86 Status of RRT for AKI in Japan Friday, February 19, 10:00-10:15 Kent Doi MD AKI & CRRT 2016 Educational Objectives: 1. Describe current RRT clinical practice for AKI in Japanese ICUs. 2. Discuss the choice of modality (CRRT vs IRRT) and optimal dose with clinical observations in Japan. Content Description: Nationwide data for the prevalence and outcomes of patients receiving renal replacement therapy (RRT) in intensive care units (ICUs) are helpful to overview clinical practice of RRT for AKI. Data extracted from the Japanese Diagnosis Procedure Combination database for 2011 revealed that CRRT was preferred especially for hemodynamically unstable patients, and in-hospital mortality of CRRT-treated AKI patients was remarkably high although the period prevalence of CRRT for AKI in Japanese ICUs was low. Two Japanese observational studies reported relatively low CRRT dose (15-20 ml/kg/hr) was not associated with any poor outcomes. In septic AKI, higher CRRT dose was associated with reduced survival rate and lower trough concentration of vancomycin and teicoplanin. Suggested Reading: 1: Iwagami M, Yasunaga H, Noiri E, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Nangaku M, Doi K. Current state of continuous renal replacement therapy for acute kidney injury in Japanese intensive care units in 2011: analysis of a national administrative database. Nephrol Dial Transplant. 2015;30: : Iwagami M, Yasunaga H, Noiri E, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Nangaku M, Doi K. Choice of renal replacement therapy modality in intensive care units: data from a Japanese Nationwide Administrative Claim Database. J Crit Care. 2015;30: : Mayumi K, Yamashita T, Hamasaki Y, Noiri E, Nangaku M, Yahagi N, Doi K. IMPACT OF CON- TINUOUS RENAL REPLACEMENT THERAPY INTENSITY ON SEPTIC ACUTE KIDNEY IN- JURY. Shock. 2016;45: : Uchino S, Toki N, Takeda K, Ohnuma T, Namba Y, Katayama S, Kawarazaki H, Yasuda H, Izawa J, Uji M, Tokuhira N, Nagata I; Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) Clinical Trial Group. Validity of low-intensity continuous renal replacement therapy*. Crit Care Med. 2013;41: : Fujii T, Namba Y, Fujitani S, Sasaki J, Narihara K, Shibagaki Y, Uchino S, Taira Y. Low-dose continuous renal replacement therapy for acute kidney injury. Int J Artif Organs. 2012;35:

87 Critical Care Nephrology: Literature Review Friday, February 19, 11:00-11:25 Noel Gibney MB FRCP(C) AKI & CRRT 2016 Educational Objectives: To discuss publications of interest over last year in Critical Care Nephrology Content Description: Bouchard J, Acharya A, Cerda J et al. A Prospective International Multicenter Study of AKI in the Intensive Care Unit. Clin J Am Soc Nephrol ;10: Hoste EA, Bagshaw SM, Bellomo R et al: Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med Aug;41(8): Yang L, Xing G, Wang L, et al. Acute kidney injury in China: a cross-sectional survey. Lancet. 2015;386(10002): Kolhe NV, Staples D, Reilly T, et al. Impact of Compliance with a Care Bundle on Acute Kidney Injury Outcomes: A Prospective Observational Study. PLoS One Jul 10;10:e Oeyen S, De Corte W, Benoit D et al. Long-term quality of life in critically ill patients with acute kidney injury treated with renal replacement therapy: a matched cohort study. Crit Care. 2015;19:289. Villeneuve PM, Clark EG, Sikora L et al. Health-related quality-of-life among survivors of acute kidney injury in the intensive care unit: a systematic review. Intensive Care Med Dec 1. [Epub ahead of print] Young P, Bailey M, Beasley R et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA. 2015;314: Srisawat N, Sileanu FE, Murugan R, et al. Variation in risk and mortality of acute kidney injury in critically ill patients: a multicenter study. Am J Nephrol. 2015;41:81-8. Kellum JA, Chawla LS, Keener C et al. The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. Am J Respir Crit Care Med Sep 23. [Epub ahead of print] Wilson FP, Shashaty M, Testani J et al. Automated, electronic alerts for acute kidney injury: a singleblind, parallel-group, randomised controlled trial. Lancet ;385(9981): Koyner JL, Davison DL, Brasha-Mitchell E et al: Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity. J Am Soc Nephrol. 2015;26: Sutherland SM, Byrnes JJ, Kothari M et al: AKI in hospitalized children: comparing the prifle, AKIN, and KDIGO definitions: Clin J Am Soc Nephrol. 2015;10: Tumlin JA, Galphin CM, Tolwani AJ et al; SCD Investigator Group: A Multi-Center, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury. PLoS One. 2015;10(8):e Zarbock A, Schmidt C, Van Aken H et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015;313:

88 EPIDEMIOLOGY AND OUTCOMES FROM AKI Abstract 1 Long Term Renal Outcomes in Critically Ill Patients with Acute Kidney Injury Hui Zhuan Tan 1, Cynthia Ciwei Lim 2, Hui Boon Tay 2, Han Khim Tan 2, Manish Kaushik 2 1 Department of Internal Medicine, Singapore General Hospital, 2 Department of Renal Medicine, Singapore General Hospital Objectives Acute kidney injury (AKI) is common in critically ill patients. We aimed to evaluate the long term renal outcome in critically ill patients with AKI. Methods This was a single-center retrospective study of adult patients admitted to the Medical Intensive Care Unit (ICU) between 1st January 2010 and 31st December 2010 in our tertiary care hospital. Patients who were dialysisdependent prior to ICU admission were excluded. AKI was defined by increment in serum creatinine >0.3 mg/dl. The outcome was progressive chronic kidney disease (CKD) defined by doubling of serum creatinine or end stage renal disease (ESRD). Results We evaluated 421 patients [median age 59.4 (IQR 46.4, 71.1) years, male 61.8%]. Median premorbid serum creatinine was 87 (66, 115) µmol/l. Most patients required mechanical ventilation (74.6%) and 141 patients (33.5%) required vasopressors. AKI occurred in 209 patients (49.6%) at ICU admission: 80 had AKIN Stage 1, 38 had Stage 2 and 91 had Stage 3 AKI. Eighty-eight patients (20.9%) received acute dialysis during their ICU stay. One hundred and three patients (41.1%) died during the hospitalization. Median follow-up was 27.7 (3.7, 34.4) months. Among 248 survivors, 28 patients (11.3%) developed progressive CKD. ESRD occurred in 13 patients at median 9.8 (0, 14.5) months. In uni-variate analysis, patients with progressive CKD were more likely to have AKI (67.9% vs. 41.4%, p=0.008) and dialysis (46.4% vs 15.0%, p<0.001). In multi-variate analysis, acute dialysis was independently associated with progressive CKD [OR 3.21 (95% CI 1.21, 8.49), p=0.02]. Conclusion Severe AKI requiring acute dialysis was associated with progressive CKD. 87

89 Abstract 2 A Systematic Review Of Health-Related Quality-Of-Life Among Critically Ill Survivors Of Acute Kidney Injury Pierre-Marc Villeneuve 1, Edward G Clark 2, Lindsey Sikora 2, Manish M Sood 2, Sean M Bagshaw 1 1 University of Alberta, 2 University of Ottawa Purpose Health-related quality-of-life (HQRL) is increasingly recognized as an important patient-centered outcome following acute illness. Among critically ill survivors suffering an episode of acute kidney injury (AKI), HRQL has been variably described. In this systematic review we summarize understanding on long-term HRQL among survivors of AKI in the intensive care unit. Methods We performed a systematic review and evidence synthesis. We included studies reporting original data that described HRQL using validated tools. The comprehensive literature search, study selection and data abstraction were performed in duplicate. Study quality was appraised. Data are primarily narratively described due to significant study heterogeneity. Results Our search yielded 2193 articles of which 18 fulfilled eligibility. Study quality was assessed as moderate to good. Six unique HRQL instruments were utilized. Follow up duration to ascertain HRQL was variable, ranging between 2 months to 15 years. HRQL among AKI survivors was significantly impaired to age/sex-matched normative population data. HRQL compared between survivors with and without AKI was similar beyond 6 months. Physical component domains were consistently more impaired compared with mental component domains. Limitations in activities of daily living, disability, and inability to return to work were common. Despite impaired HRQL, most survivors would receive similar treatment again, including renal replacement therapy if necessary. Conclusion Among critically ill survivors whose course was complicated by AKI, HRQL was universally impaired when referenced to population norms; however, was comparable to those without AKI. Physical limitations and disabilities were commonly described by patients compared with psycho-social limitations. Despite this, most survivors perceived their HRQL as acceptable and would undergo similar therapy again. 88

90 3 Epidemiology of AKI Requiring Dialysis in Critically Ill Children Genevieve Morissette 1, Wassim Kechaou 1, Catherine Litalien 1, Aicha Merouani 1, Veronique Phan 1, Philippe Jouvet 1, Josee Bouchard 1 1 University of Montreal Introduction: Previous pediatric studies on dialysis in acute kidney injury (AKI) suggest that the mortality rate is mainly related to the underlying diagnosis or multiple organ failure rather than to a specific dialysis modality or other risk factors. Fluid overload before dialysis also seems to influence mortality. Our objective was to identify the most important risk factors of 28-day mortality at dialysis initiation. Methods: We conducted a retrospective cohort study in a tertiary care pediatric center. All critically ill children who underwent acute continuous renal replacement therapy (CRRT) or intermittent hemodialysis for AKI between 1998 and 2008 were included, excluding those with chronic kidney disease. A case report form was developed and specific risk factors were identified using an item generation item selection modality. Results: We enrolled 70 consecutive patients. The main ICU admission reasons were respiratory failure (34%), septic shock (29%), AKI (24%) and post-operative (21%). The most frequent underlying diseases were bone marrow transplant (24%) and solid organ transplant (17%). The majority of patients received CRRT only. Thirty-three patients (47%) died within 28 days after ICU admission. The median age (8.9 years [IQR ]), weight (28 kg [8-45]), PEdiatric Logistic Organ Dysfunction score (PELOD) (21 [20-32]), Pediatric Index of Mortality 2 (PIM 2) (8 [7-29]), creatinine (102 umol/l [70-155]), vasoactive score (3 [0-47]) and oxygenation index (7 [4-19]) at ICU admission were similar between survivors and non-survivors. We identified these risk factors of mortality in univariate analyses: hematological underlying disease and factors at dialysis initiation including: fluid overload 20%, PELOD score 20 and higher creatinine. Of these, only PELOD score 20 was significant in the multivariate logistic regression analysis (OR 4.5;95%CI ;p=0.01). After ICU discharge, 12 out of 35 survivors needed dialysis. Among 31 survivors at hospital discharge, 3 required dialysis. Discussion: Despite improvement in patient care, almost half of our patients with AKI requiring dialysis died within 28 days. Our data suggest that a higher severity of illness is the most important risk factor of mortality in AKI requiring dialysis. Conclusion: In our pediatric study, only the severity of illness, as measured by the PELOD score before initiation of dialysis, was independently associated with an increased risk of mortality. 89

91 4 A Multicenter Population-based Epidemiological Study of Intensive Care Unit (ICU) Acquired Acute Kidney Injury (AKI) in a Brazilian Amazon Region FERNANDO F MELO 1, MAGELA MAGELA 2, ANA CAROLINE F BEZERRA 2, GUSTAVO NEVES 2, EMMANUEL BURDMANN 3, DIRCE M ZANETTA 1 1 University of Sao Paulo- School of Public Health, 2 Acre Federal University, 3 University of Sao Paulo Medical School Purpose of the study: Prospective epidemiological data on AKI in developing countries is scarce. This study was designed to assess the incidence of ICU-acquired AKI in the Amazon Region in Brazil. Methods used: Prospective data on all adult patients admitted in all ICUs of the Western Amazon region (600 square kilometers and 800,000 inhabitants) were collected for 11 months during 2014 and Patients < 18 years old, chronic kidney disease stage 5, kidney transplant or ICU stay < 48 h were excluded. AKI was diagnosed by KDIGO criteria and mortality was assessed 30 and 180 days after ICU discharge. Summary of the results: During the study period, 824 patients were ICU admitted and 642 fulfilled selection criteria. AKI incidence was 38% and was associated with age (OR 1.11 for each 5 year increase, p < 0.001) previous fluid balance > 1,500 ml/24h (OR 2.3, p = 0.017), mechanical ventilation (OR 1.7, p = 0.018) and surgery (OR 0.38, p = 0.017). The main reasons for ICU admission in patients who developed AKI were hemodynamic instability (22.3%), respiratory failure (18.6%), surgery (17.8%), neurological diseases (14.2%), and sepsis (9.3%). Only 2.3% had tropical diseases. There were significant association between AKI and mortality during ICU stay (42% vs 27%, p<0.001) and mortality within 30 days after ICU discharge (10% vs 6%, p=0.046). AKI mortality during ICU stay was associated with mechanical ventilation (OR 3.5, p < 0.001), use of vasoactive drugs (OR 2.6, p < 0.001), age (OR 1.07for each 5 years increase, p = 0.017) and surgery (OR 0.54, p = 0.017). Conclusion reached: AKI has a high incidence and mortality rate in ICU patients of the Western Amazon area. Causes of ICU admission and risk factors for AKI in this study did not differ from those seen in developed countries. The lack of tropical diseases-associated AKI might be due the particular conditions of the Amazon area, with rivers not navigable most of the year, long rain period making difficulty access to larger cities and poor health services infrastructure in remote areas. 90

92 5 Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN): Incidence and Outcomes from an International Multi-center Cohort Study Jennifer G Jetton 1, Louis J Boohaker 2, David J Askenazi 2 1 University of Iowa, 2 University of Alabama, Birmingham, AL, USA On behalf of the Neonatal Kidney Collaborative Background: Single center studies report neonatal acute kidney injury (AKI) incidence 12-70%; neonates with AKI appear to have worse outcomes. These findings prompted the formation of the Neonatal Kidney Collaborative (NKC) to improve our understanding of neonatal AKI. Objective: Assess the incidence of neonatal AKI and its association with outcomes in a large, multi-center cohort. Design/Methods: NKC includes 24 institutions from 4 countries (USA, Canada, Australia and India). NICU admissions from Jan 1, 2014 to Mar 31, 2014 were screened; data from 20 centers are presented. Inclusion criteria: 1) admission during the study period, 2) need for intravenous fluids 48 hrs. Exclusion criteria: 1) admission at > 2 weeks of age, 2) congenital heart disease requiring surgical repair at < 7 days of age, 3) lethal chromosomal anomaly, 4) death within 48 hours of admission. AKI was defined using the KDIGO SCr based definition: a rise in SCr of 0.3 mg/dl or a 50% rise from baseline = stage 1; 100% rise = stage 2, and 200% rise = stage 3. Baseline SCr = lowest previous value. Results: Of 3397 screened neonates, 1742 (51%) met study criteria. Of these, 960 (55%) had at least 2 SCr measured and were included in the analyses. 192/960 (20%) developed AKI: stage 1 =22%; stage 2 = 28%, stage 3 =50%. Compared with patients without AKI, those with AKI were more likely to die, have neurologic, cardiovascular, pulmonary, infectious, and renal diagnoses, and be hospitalized 120 days (Table). 10% (N=20) of those with AKI received renal replacement therapy. Conclusions: The AWAKEN study demonstrated an AKI incidence of 20%. Those with AKI are at risk for significant clinical outcomes. Further analysis of this robust database is underway. Outcomes by AKI stage AKI 0 (n=768) AKI 1 (n=41) AKI 2 (n=54) AKI 3 (n=97) p-value Status at <120 days <0.0001* Home 609 (80%) 22 (54%) 30 (56%) 44 (45%) Still in NICU 26 (3%) 1 (2%) 13 (24%) 21 (23%) Transferred Convalescent Care 87 (11%) 5 (12%) 4 (7%) 17 (18%) Transferred Escalation of Care 13 (2%) 2 (5%) 4 (7%) 3 (3%) Died 31 (4%) 11 (27%) 3 (6%) 12 (12%) Discharge Diagnoses Cardiovascular 144 (19%) 18 (44%) 33 (61%) 44 (45%) <0.0001* Pulmonary 82 (11%) 12 (29%) 25 (46%) 41 (42%) <0.0001* Neurological 144 (19%) 16 (39%) 18 (33%) 28 (29%) <0.0004* Renal 62 (8%) 15 (34%) 21 (39%) 47 (49%) <0.0001* Infection 181 (24%) 16 (39%) 22 (41%) 33 (34%) * 91

93 6 Risk factors for Neonatal Acute Kidney Injury: Results from the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study Jennifer G Jetton 1, Jennifer R Charlton 2, Louis J Boohaker 3, Alison L Kent 4, David J Askenazi 3 1 University of Iowa Children's Hospital, 2 University of Virginia, Charlottesville, VA, USA, 3 University of Alabama, Birmingham, AL, USA, 4 Centenary Hospital for Women and Children and Australian National University Medical School, Canberra, Australia On behalf of the Neonatal Kidney Collaborative Background: The risk of neonatal acute kidney injury (AKI) is as high as 70% in select subpopulations. However most reports are from single-center studies, making generalizability difficult. Objective: The aim of this study was to determine the risk factors for neonatal AKI using the largest multicenter international cohort of neonates derived from 20 institutions participating in the AWAKEN study conducted by the Neonatal Kidney Collaborative. Design/Methods: AWAKEN is a retrospective cohort study of all neonates who were admitted to the NICU from January 1- March 31, 2014 requiring intravenous fluids for > 48 hours and who met the inclusion and exclusion criteria. AKI was defined according to the neonatal KDIGO definition limited to serum creatinine. Results: Of the 3397 neonates screened, 1742 met the inclusion criteria and 960 had >1 serum creatinine measurement. AKI (stages 1-3) was identified in 192 neonates. Maternal and neonatal risk factors that separated neonates with and without AKI are listed in the Table. Conclusions: This is the first multi-center international study to evaluate the risk factors associated with neonatal AKI. Many of these results are consistent with the single-centre studies reported in the literature. The data will require further stratification tailoring the risk factor analyses for subpopulations of neonates. Using the AWAKEN cohort, we plan to develop and validate risk stratification models which can be used in future prospective studies to aid in the early identification of neonatal AKI. Risk Factor MATERNAL CHARACTERISTICS no AKI, n=768 (%) AKI, n=192 (%) p value maternal hemorrhage 19 (2) 12 (6) 0.01 antenatal steroids 290 (38) 99 (52) assisted conception 43 (6) 22 (11) 0.01 maternal age (years) 28 (+/-6) 27 (+/-5) oligohydramnios 36 (5) 17 (9) 0.02 PERINATAL EVENTS oxygen for resuscitation 367 (48) 124 (65) < positive pressure ventilation 397 (52) 140 (66) < intubation 191 (25) 119 (62) < chest compression 39 (5) 21 (11) < NEONATAL CHARACTERISTICS Apgar 1 min 7 (4, 8) 4 (2, 7) < Apgar 5 min 8 (7, 9) 7 (6, 8) < gestational age <35 weeks 406 (53) 136 (71) <

94 birthweight <1500 g 118 (24) 116 (60) < length (cm) 44.4 (+/-6) 38.6 (+/-8) < head circumference (cm) 30.9 (+/-4) 27.1 (+/-5) < respiratory failure 384 (50) 140 (73) < congenital heart disease 30 (4) 16 (8) Low Pre-operative Serum Bicarbonate Levels Predict Acute Kidney Injury after Cardiac Surgery Seohyun Park 1, Youn Kyung Kee 1, Su-Young Jung 1, Seung Hyeok Han 1, Tae-Hyun Yoo 1, Shin-Wook Kang 1, Jung Tak Park 1 1 Department of Internal Medicine, Yonsei University College of Medicine Purpose: Acute kidney injury (AKI) after cardiac surgery is a common and serious complication, and is associated with high mortality rates. There is evidence showing that metabolic acidosis induce decline of glomerular filtration rate (GFR) in associated with activation of intrarenal renin-angiotensin system. Whether pre-operative serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery is not well known. Therefore, the aim of this study was to identify the clinical implications of pre-operative serum bicarbonate levels on AKI occurrence after cardiac surgery. Methods: Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. Serum bicarbonate levels and creatinine concentrations within 96 hours before cardiac surgery were adopted for preoperative values. The patients were categorized into three groups according to preoperative serum bicarbonate levels; group 1 (n=193), <23 meq/l; group 2 (n=226), meq/l; group 3 (n=456), >24 meq/l. Primary outcome was incidence of AKI at 48 hours after cardiac surgery. AKI was defined by the Acute Kidney Injury Network criteria. Multiple logistic regression analysis was performed to find risk factors of AKI occurrence. Results: The mean age was 60.5 years, and 518 (59.2%) patients were male. 228 patients (26.1%) developed AKI at 48 hours after cardiac surgery [stage 1, 173 (19.8%); stage 2, 28 (3.2%); stage 3, 27 (3.1%)]. Incidence of AKI was higher in group 1 (34.6%) than group 2 (26.3%) and group 3 (39.0%) (P < 0.001). In addition, the duration of postoperative ICU stay was longer in AKI patients [AKI patients (6.2 days) vs. non-aki patients (2.7 days), P<0.001] and in the low preoperative serum bicarbonate level groups [group 1 (4.4 days), group 2 (3.6 days), group 3 (3.3 days), P<0.001]. In multivariate logistic regression analysis, low pre-operative serum bicarbonate levels were significantly associated with AKI even after adjusting for age, sex, history of hypertension, history of diabetes mellitus, operation type, hemoglobin levels, and GFR. [group 1 vs. group 3, odds ratio=2.36, 95% confidence interval= , P<0.001]. Conclusion: Correction of low serum bicarbonate levels before cardiac surgery may reduce the risk of AKI development. 93

95 8 A clinical risk model to predict acute kidney injury after cardiac surgery in Chinese patients Wuhua Jiang 1, Xiaoqiang Ding 1, Yi Fang 1, Jiarui Xu 1, Chunsheng Wang 2, Jie Teng 1 1 division of nephrology,zhongshan hospital,shanghai, 2 division of cardiac surgery,zhongshan hospital,shanghai Objective: To establish and validate a risk model to predict AKI after cardiac surgery (AKICS) based in Chinese patients. Methods: 7233 patients who underwent cardiac surgery (CABG,OPCAB, valve surgery or CABG with/without valve surgery)in the department of cardiac surgery in our centre between Jan,2010 and April,2013 were included. Logistic regression was used to analyze the incidence and preoperative risk factors of AKICS among 6081 patients, and a specific number of points were assigned to each risk factor according to the odds ratio (OR) observed, the other patients were set for validation, by means of Hosmer Lemeshow goodness-of-fit test for the calibration and receiver operation characteristic(roc) curves with area under ROC curve(auroc) for the discrimination. Results: The incidence of AKI and RRT after cardiac surgery in the derivation cohort were 23.8% (1446/6081) and 1.5% (93/6081) respectively. The mortality of derivation cohort was 2.8% (170/6081). According to the logistic regression: male(or=2.277),atrial fibrillation(or=1.766),preoperative kidney disease(without RRT)(OR=3.904), preoperative coronary angiography(or=1.137),nyha>2(or=1.457), were recognized as independent risk factor for AKI after cardiac surgery. The risk model was categorized to high risk cohort (total score 8) and low risk cohort (total score 9-12), the risk of AKI in the derivation cohort was 35.6% (low risk cohort) vs 83.4%(high risk cohort). The AUROC for AKICS of the validation cohort was 0.81,which meant a good discrimination, and Hosmer Lemeshow goodness-of-fit test (χ2=10.13,p=0.256) showed a proper calibration. Conclusions: The risk model based upon chinese patients, with AKI being defined with the 2012 KDIGO AKI guideline is established and proper prediction value for AKICS is validated. 94

96 9 Subclinical Acute Kidney Injury is an Early Stage of AKI Rolando Claure-Del Granado 1, Vania Prudencio-Ribera 1, Susana Ledezma-Montan 1, Ravindra L Mehta 2 1 Hospital Obrero #2, CNS. Universidad Mayor de San Simon, School of Medicine, 2 University of California San Diego, School of Medicine. Background: A recent ADQI consensus conference on utilizing biomarkers in AKI has suggested that novel biomarkers such as NGAL, KIM-1, and IGFBP-7 can identify kidney damage prior to elevations in serum creatinine (scr). Combining damage and functional markers can thus permit recognition of an early stage of AKI termed subclinical AKI. In this study we tested the hypothesis that a panel of damage biomarkers could detect subclinical AKI and would predict the subsequent development of clinical AKI. Methods: We included 50 consecutive patients admitted to a Medical ICU. Daily scr, urine albumin (ualb) and urine β2 Microglobulin levels were measured each 24 hours for 7 consecutive days; we also evaluated urine sediment and assigned a score from 1 to 3 using Perazella et al criteria. We define subclinical AKI if any of the following criteria was reached in the absence of alterations in scr: a) new onset of albuminuria ( 15 mg/l), or b) β2-microglobulin ( 3.2 mg/l), or c) a urinary sediment score 2. Clinical AKI was defined by KDIGO scr criteria. We analyzed the predictive value of each of these biomarkers for the subsequent development of clinical AKI as well to predict survival. Results: Of the 50 patients, 11 (22%) did not develop AKI while 39 (78%) developed incipient AKI that progressed to clinical AKI in 26 (67%) while 13 (33%) did not have a rise in scr. The rise in ualb levels and β2-microglobulin levels at 24 and 48 h. predicted the development of clinical AKI (ualb AUC (95% CI ), p = 0.02; and β2-microglobulin (95% CI ), p=0.010) at 24 h; and ualb (95% CI ), p=0.012; and β2-microglobulin (95% IC ), p=0.14 at 48 h; respectively). A urinary sediment score 2 at 24 and 48 h equally predicted the development of clinical AKI; AUC (95% IC ), p=0.001 and (95% IC ), p=0.006, respectively. 28 day mortality did not differ between patients with subclinical AKI who didn t developed clinical AKI and patients with subclinical AKI who developed clinical AKI. Conclusions: Our data shows high incidence of subclinical AKI that progressed to clinical AKI. These findings support the ADQI recommendations to consider subclinical AKI based on positive damage biomarkers alone as an early phase of AKI. Identification of incipient AKI would potentially allow earlier intervention with preventive and treatment strategies to reverse kidney injury and improve recovery. 95

97 10 High Level of Plasma Pro-Enkephalin (penkid) in the General Population Predicts Deterioration of Kidney Function and Incidence of Chronic Kidney Disease Christina-Alexandra Schulz 1, Ulrika Ericson 1, Peter Almgren 2, George Hindy 1, Peter M Nilsson 3, Joachim Struck 4, Andreas Bergmann 4, Olle Melander 5, Marju Orho-Melander 1 1 Department of Clinical Sciences, Diabetes and Cardiovascular Disease - Genetic Epidemiology, University Hospital Malmo Clinical Research Center, Lund University, Malmo, S, 2 Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden, 3 Department of Clinical Sciences, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden, 4 sphingotec GmbH, Hennigsdorf, Germany, 5 Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden Purpose of the study: Recently, elevated plasma Pro-Enkephalin (penkid), a stable surrogate marker for Enkephalins, has been associated with decreased estimated glomerular filtration rate (egfr) in acute disease settings. Here we examined if penkid predicts incident chronic kidney disease (CKD) and decline of renal function in a prospective general population cohort without CKD at baseline. Methods: The background population for this study is the population-based Malmö Diet and Cancer Study (MDC) of which 28,098 subjects participated in the baseline examination between 1991 and In a random sample (n=2,568) of subjects without CKD (egfr > 60 ml/min/1.73 m2) at inclusion the relationship between penkid concentration at baseline and presence of CKD at follow-up re-examination as well as the association of penkid with yearly change in egfr, plasma creatinine and plasma Cystatin C was examined. Results: During a mean follow-up time of 16.6 years, 31.7% of the subjects developed CKD. Among participants in the highest versus the lowest tertile of penkid concentration at baseline the OR for CKD was 1.50 (95% CI ) after adjusting for age, sex, follow-up time, and baseline levels of egfr, fasting glucose, BMI, antihypertensive treatment and systolic blood pressure. The yearly mean decline of egfr as well as the yearly rise of cystatin C and creatinine were significantly higher among participants with penkid levels in the highest tertile (P-trend=0.0003, and ). Through genome-wide association analysis in 4,150 participants of the same cohort we identified one locus with 24 SNPs located up- or downstream of the PENK gene that associated with penkid concentration (P<5x10exp-8). The strongest association was observed for rs where the T minor allele associated with pmol/l higher penkid levels per allele (P=4.666exp-21). The T- allele associated with 19% increased risk of CKD per minor allele (P=0.03). Conclusions: Circulating plasma concentration of penkid predicts incident CKD and may be useful in identifying subjects in need of pharmacological and non-pharmacological primary preventive regimens. In addition, the Mendelian Randomization analysis suggests that the relationship between penkid levels and incident CKD could be causal. 96

98 11 A Worldwide Multicentre Evaluation of Acute Kidney Injury in Septic and Non-septic Critically Ill Patients: The Intensive Care Over Nations (ICON) Audit Esther Peters 1, Hassane Njimi 2, Peter Pickkers 1, Jean-Louis Vincent 2 1 Radboud university medical center, Nijmegen, The Netherlands, 2 Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Introduction: Acute Kidney Injury (AKI) is a serious complication in hospitalized patients, particularly in the critically ill, in whom AKI is independently associated with poor prognosis and outcome. Sepsis is the most important cause of AKI and its pathogenesis is clearly distinct from non-septic AKI. Here, we compared the clinical course and outcome in septic and non-septic critically ill patients worldwide. Methods: Intensive Care Units (ICUs) were invited to participate voluntarily in the Intensive Care Over Nations (ICON) audit. In participating centers, data was prospectively collected from all adult patients (>16 years) admitted to the ICU during a 10-day period. Patients admitted for less than 24h for routine postoperative surveillance were excluded. Data was collected daily during the ICU stay up to 28 days, with a follow-up for outcome data until hospital discharge or death. AKI was defined according to the Risk, Injury, Failure, Loss and End-Stage (RIFLE) classification and was diagnosed during the first 48h after ICU admission. Patients with pre-existent chronic renal failure (CRF) were analyzed as a separate subgroup. Results: The study population comprised 9579 patients. At admission, 30% of patients fulfilled sepsis criteria of which 67% developed AKI, compared to 57% in the non-septic population (p<0.0001). AKI was more severe in septic patients and these patients were less likely to recover to a lower RILFE category compared to non-septic patients (improvement between day 3 and day 7 in 22 vs. 32%, p<0.0001). Dialysis incidence was higher in septic patients compared to non-septic patients (21% vs. 5%, p<0.0001). Also in-hospital mortality rates were higher (33% vs. 14%, p<0.0001), which increased to 51% in septic and 35% in non-septic AKI-F patients. Hospital mortality of septic AKI-F patients was similar compared to septic patients with pre-existent CRF (HR 1.6, 95%CI compared to 1.8, 95%CI in septic AKI-F patients). Septic patients with AKI-R or AKI-I that improved between day 3 and day 7 after admission showed a similar mortality compared to septic patients who did not develop AKI, while mortality remained elevated in AKI-F patients that improved between day 3 and 7. Cumulative survival curves are presented in Figure 1. Conclusion: AKI in sepsis is more severe, less likely to recover and associated with a higher mortality, compared to non-septic AKI. 97

99 12 Progression of Chronic Kidney Disease and Cardiovascular Outcomes After Cardiac Catheterization Associated-Acute Kidney Injury and Comparison with Population Controls Richard R Solomon 1, Jeremiah J Brown 2, R. Brooks Robey 3, Meg Plomondon 4, Thomas M Maddox 4, Elizabeth L Nichols 1, Michael E Matheny 5, Thomas T Tsai 6, John S Rumsfeld 4, Mark J Sarnak 6 1 Section of Nephrology, Fletcher Allen Health Center, University of Vermont, Burlington, VT, 2 The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, 3 Section of Nephrology and Research and Development Service, White River Junction Veterans Affairs Medical Center, Veterans Administration, White River Junction, VT, 4 VA Eastern Colorado Health Care System; University of Colorado School of Medicine, Denver, CO, 5 Geriatrics Research, Education, and Clinical Care, Tennessee Valley Healthcare System, Veteran's Administration, Nashville, TN, 6 Institute for Health Research, Kaiser Permanente Colorado University of Colorado, Denver Colorado Denver VA Medical Center, Denver Colorado, 6 Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA Purpose of the study: Studies of chronic kidney disease (CKD) progression following Acute Kidney Injury (AKI) have largely relied on administrative data. We investigated the association between AKI and CKD progression using laboratory data and long-term endpoints in a national U.S. cohort with matched population controls. We hypothesized there is an association between AKI and CKD progression. Methods: All Veterans Affairs (VA) patients undergoing percutaneous coronary intervention (PCI) in the VA Clinical Assessment, Reporting, and Tracking Program between were studied. A matched control group was derived from patients unexposed to cardiac catheterization during the same time period. AKI was defined as an absolute (0.5 mg/dl) or relative (25%) increase in serum creatinine or dialysis within 7-days. CKD progression was defined as an increase in CKD stage by two independent laboratory measures at least 90- days apart, or new onset of dialysis or hospitalization for renal failure. Time to event analyses were conducted using Kaplan-Meier and Cox proportional hazards modeling. Results: There were 21,254 PCI patients and 96,660 controls. AKI developed in 13% of PCI patients. Patients developing AKI, not developing AKI, and controls had a CKD progression incidence (per 100 person years), 11.14, and 6.58, respectively. Compared to controls, PCI patients with or without AKI were more likely have CKD progression in adjusted analyses (AKI: %CI 3.88, 4.42, p < 0.001; No AKI: %CI 1.68, 1.80, p < 0.001). Among patients with CKD prior to PCI, AKI was associated with a 11-fold (9.36, 12.18) increased likelihood of progression of CKD over controls. Similar results were observed for other postdischarge events, including dialysis, AMI, and all-cause mortality. Conclusions: Patients developing AKI following PCI exhibited more rapid CKD progression, dialysis, AMI, and mortality outcomes than both PCI patients without AKI and matched controls. Image on following page 98

100 13 Plasma Pro-Enkephalin and Poor Long-Term Outcome in Renal Transplant Recipients Lyanne M Kieneker 1, Joachim Struck 2, Ron T Gansevoort 1, Michel M Joosten 1, Rodolf A de Boer 3, Oliver Hartmann 2, Andreas Bergmann 2, Stephan J Bakker 1 1 Internal Medicine, Nephrology, UMC Groningen, Netherlands, 2 sphingotec GmbH, Hennigsdorf, Germany, 3 Cardiology, UMC Groningen, Netherlands Purpose of the study: Enkephalins are well-known endogenous opioid peptides. Recent evidence indicates that they are not only involved in regulation of pain, but also in homeostasis of the immune system and the circulation. Pro- Enkephalin (penkid) is stable in plasma and has been established as reliable surrogate marker for the unstable enkephalins. Recent studies found associations of penkid with acute kidney injury and prognosis after myocardial infarction. We aimed to investigate whether plasma penkid could be linked to chronic kidney disease and poor long-term outcome in renal transplant recipients (RTR). Methods: We included 664 RTR who were 8.1±7.6 years after transplantation. Plasma levels of penkid were measured with a double monoclonal sandwich immunoassay. continued on following page 99

101 Results: Mean age was 53±13 years, 56% were male, estimated glomerular filtration rate (egfr) was 49 ml/min/1.73m2 (interquartile range [IQR]: ml/min/1.73m2) and urinary albumin excretion (UAE) was 40 mg/24h (IQR: mg/24h). Median penkid was 110 pmol/l (IQR: pmol/l). penkid was correlated with both egfr (r=-0.73, P<0.001) and UAE (r=0.35, P<0.001). During a median follow-up of 3.1 years (IQR: years), 45 RTR developed graft failure and 76 died. penkid was both associated with increased risk of graft failure (hazard ratio per standard deviation increment of the logarithm of penkid, 2.76; 95% CI, ) and all-cause mortality (HR=1.83; 95%CI, ), independent of age, sex, egfr, and UAE. These associations remained materially unchanged after additional adjustment for body mass index, alcohol consumption, smoking, systolic blood pressure, antihypertensive drug use, use of calcineurin inhibitors, and high-density lipoprotein. penkid also predicted the composite outcome graft failure and mortality (HR=2.24; 95% CI, ), independent of age, sex, egfr, and UAE. Conclusions: High concentrations of penkid are linked to chronic kidney disease as reflected by correlations with egfr and UAE. In addition, penkid was independently associated with increased risk of graft failure and mortality in RTR. Plasma penkid is an interesting new biomarker which may aid in early identification of RTR at risk for late graft failure and premature mortality. 14 Hospital Re-admission and Post-discharge Mortality in Critically Ill patients with Acute Kidney Injury Peishan Lee 1, Cynthia Ciwei Lim 1, Hui Boon Tay 1, Han Khim Tan 1, Manish Kaushik 1 1 Department of Renal Medicine, Singapore General Hospital, Singapore Introduction Acute kidney injury (AKI) in critically ill patients is associated with increased in-hospital mortality. We aimed to evaluate its impact on post-discharge mortality and hospital re-admission rates. Methods Retrospective cohort study of adults admitted to the medical intensive care unit (MICU) in a tertiary care hospital between 1 January 2010 and 31 December Patients were excluded if they were dialysisdependent prior to MICU admission. Patients' demographic, co-morbidity and laboratory data were obtained from electronic medical records. AKI was present if serum creatinine increased >0.3 mg/dl (26.4 mcmol/l) from baseline. Outcomes studied were hospital re-admission and post- discharge mortality. Results We studied 421 patients: median age 59.4 years (IQR: 46.4, 71.1 years), male 61.8%.Comorbidities included diabetes mellitus (DM) 26.8%, hypertension 39.7%, ischemic heart disease (IHD) 20.9%, chronic liver disease or cirrhosis 5.7% and active malignancy 27.1%. Premorbid MDRD egfr was 72.9 (47.7, 102.2) ml/min/

102 m2. AKI was present in 209 patients (49.6%) at ICU admission (91 patients with Acute Kidney Injury Network Stage 3 AKI) and 173 (41.1%) died. Median follow up for the 248 survivors was 27.7 (3.7 to 34.4) months. 155 patients (62.5%) had a hospital readmission at median 2 (1, 7) months after discharge. After adjusting for age, gender, DM, hypertension, IHD, liver cirrhosis, chronic lung disease, active malignancy, premorbid serum creatinine, need for mechanical ventilation and vasopressor at ICU admission and AKI, only age was independently associated with hospital readmission [adjusted OR 1.03, 95% CI (1.01, 1.05), p=0.009]. Fifty-two patients (21.0%) died at 7 (2 to 21) months after discharge. Male gender [adjusted OR 2.64, 95% CI (1.18, 5.90), p=0.02] and active malignancy [2.55 (1.16, 5.61), p=0.02] were independently associated with post-discharge death. AKI at ICU admission was not different between patients with (45.8%) and without hospital readmissions (41.9%), p=0.59; nor between patients with (32.7%) and without post discharge mortality (47.4%), p=0.06. Conclusion AKI was not associated with hospital re-admission and post-discharge death in this cohort of critically ill patients. 15 The Association of Plasma Pro-Enkephalin with Renal Function Decline Lyanne M Kieneker 1, Oliver Hartmann 2, Joachim Struck 2, Ron T Gansevoort 1, Michel M Joosten 1, Rudof A de Boer 3, Andreas Bergmann 2, Stephan J Bakker 1 1 Internal Medicine, Nephrology, UMC Groningen, Netherlands, 2 sphingotec GmbH, Hennigsdorf, Germany, 3 Cardiology, UMC Groningen, Netherlands Purpose of the study: Enkephalins are well-known as small endogenous opioid peptides. Recent evidence indicates that they are not only involved in regulation of pain, but also play roles in the periphery in homeostasis of the immune system and the circulation. Pro-Enkephalin (penkid) is stable in plasma and has been established as reliable surrogate marker for unstable enkephalins. Observational studies found associations of penkid with acute kidney injury and chronic renal failure. We therefore aimed to prospectively examine the association of penkid with renal function decline in a population-based cohort. Methods: We studied 5,544 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women aged years. Plasma levels of penkid at baseline were measured with a double monoclonal sandwich immunoassay. Estimated glomerular filtration rate (egfr) was measured at baseline, after 2.3±0.3 years, 5.1±0.6 years, and 7.7±0.9 years, and were LNtransformed. Linear mixed models were used to define individual egfr slopes. Next, multivariable linear regression of penkid was performed with the individual egfr slopes as outcome, with adjustment for potential confounders. 101

103 Results: At baseline, mean age was 53±13 years, 50.4% were male, and egfr was 94 ml/min/1.73m2 (interquartile range [IQR]: ml/min/1.73m2). Baseline median penkid was 52 pmol/l (IQR: pmol/l). penkid was correlated with baseline egfr (r=-0.44, P<0.001). The geometric mean of individual egfr slopes was ±0.95 ml/min/1.73m2 per year. Log-transformed penkid was significantly associated with annual decline in egfr (st.β=-0.133; P<0.001; R2=0.02). This association remained significant after adjustment for age, sex, baseline egfr, smoking, alcohol consumption, high-density lipoprotein, systolic blood pressure, and urinary creatinine and albumin excretion (st.β=-0.032; P=0.04; R2=0.25). Conclusion: In this population-based cohort, penkid was significantly associated with renal function decline. This association was independent of potential confounders. Measurement of penkid could be a helpful tool to guide measure preventing renal function decline. 16 Furosemide Stress Test, Renal Angina Index, and Urinary Sediment: Which I Should Use to Predict AKI? Daniela Torrico-Guillen 1, Ivan Chavez-Mostajo 1, Marcelo Coca-Villarroel 1, Alex Arauco-Meneses 1, Lety Castro-Cossio 1, Rolando Claure-Del Granado 1 1 Hospital Obrero #2 - CNS; Universidad Mayor de San Simon, School of Medicine; Cochabamba, Bolivia Background: In recent years several approaches for identifying patients at risk of AKI were used; among them two have been of increasing interest: the furosemide stress test (FST) and the renal angina index (RAI). We recently used Perazella et al urinary sediment score (USS) to predict subsequent development of clinical AKI. All of these approaches aim to delineate patients at risk for subsequent severe AKI (AKI beyond the period of functional injury) versus those at low risk. We aimed to assess the performance of these three different ways to identify patients at risk of subsequent severe AKI in an ongoing cohort of adult critically ill patients at risk of AKI. Methods: We analyzed data from 30 hospitalized patients admitted to our Medical ICU. We measured serum creatinine (scr) every 24 hours for 7 consecutive days following ICU admission, and urinary volume was assessed hourly each 24 hours. At admission (day 0) and 24 hours after (day 1): a) the RAI was calculated at ICU using the following formula: Risk level (presence of sepsis (yes or no), use of vasopressors and use of invasive mechanical ventilation, and presence of diabetes mellitus, and) x Injury level (changes in kidney function based on egfr); b) we evaluate the USS (Perazella et al); and c) we applied the FST (as describe by Chawla et al in Crit Care 2013 Sep 20; 17(5):R207) at ICU admission (day 0). We assessed the performance of these 3 tests to predict the subsequent development of AKI using KDIGO scr and urinary volume criteria. Results: Of the 30 patients included in this study, 4 (13.3%) patients met the primary end point of AKI diagnosis (using scr KDIGO criteria). The performance of the two different scores and the test were as follows: RAI had the best performance with a ROC AUC of 1.00(p = 0.002); followed by FST with a ROC AUC of (p = 0.002) but we consider a cut-off point of <600 cc of urine at 2 hours since none of the patients who developed AKI had <200 cc of urine as the original cut-off value proposed by Chawla et al; finally the use of USS ( 2) had a ROC AUC of (p = 0.002). The sensitivity, specificity, PPV and NPV of the 3 tests used 102

104 are shown on table 1. Conclusions: The 2 scores (RAI and USS) and the furosemide stress test have robust predictive capacity to identify critically ill patients at high risk of developing AKI before a rise in serum creatinine occurs. These preliminary data of our ongoing study warrants future studies to validate these findings. Furosenide Stress Test Renal Angina Index Urinary Sediment Score Sensitivity (%) Specificity (%) PPV (%) NPV (%) The Role of Bioimpedance Analysis as a Predictor of Outcomes in Acute Kidney Injury Patients Requiring Renal Replacement Therapy Sadudee Peerapornratana 1, Khanitha Yimsangyad 1, Srisuda Sripeng 1, Nattachai Srisawat 1 1 Chulalongkorn University, Bangkok, Thailand Background: Fluid overload is one of the independent risk factor for mortality in acute kidney injury (AKI) patients. Bioimpedance analysis (BIA) is a promising tool for quantifying volume status in end stage renal disease. However, the role of BIA in estimation fluid balance and predictor outcome in acute kidney injury (AKI) is still unclear. This prospective cohort study aims to investigate the role of BIA as a predictor of mortality in AKI patients. Methods: We enrolled adult patients with severe AKI who underwent continuous renal replacement therapy (CRRT) or sustained low-efficiency dialysis (SLED) admitted in intensive care units (ICUs) of King Chulalongkorn Memorial Hospital from October 2013 to February Baseline characteristics including actual body weight were recorded. Volume status was estimated by fluid accumulation from admission to study date (a total input fluid minus total output fluid). We tested multi-frequency BIA within 24 hours after RRT initiation. The primary outcome was 28-day mortality. Results: A total of 41 critically ill patients were included in this study (49% are male). Mean body weight at admission was 60.2 kg. Twenty-three patients (56%) were dead within 28 days. Mean body fluid accumulation was 3.98 ± 3.88 and 4.67 ± 5.73 liters (7.10% ± 7.09% and 7.45% ± 8.68% compared to body weight at admission) in survival and non-survival group, respectively (p=0.663), while mean excess fluid from BIA was 4.73 ± 3.12 and 5.50 ± 6.27 liters (p=0.637). The correlation (r) between body fluid accumulation and excess fluid from BIA is (p<0.001). The ROC curve of fluid accumulation and excess fluid by BIA for predict 28-day mortality were and 0.499, respectively. Conclusions: Fluid accumulation and excess fluid from BIA has a good correlation in AKI patients requiring RRT. However, this two methods of volume status estimation are poor predictor for 28-day mortality in these patients. Figure on following page 103

105 18 Evolution of AKI Treatment in ICU in 2 Hospitals of Piedmont (Italy) in The Last 15 Years: Analysis of Outcome, Progression Toward CKD and RRT Modality. Marita Marengo 1, Maddalena Coaloa 2, Alessandro D Quercia 3, Sergio Dellepiane 3, Marco Formica 1, Alfonso Pacitti 4, Vincenzo Cantaluppi 5 1 Nephrology and Dialysis Unit, ASLCN1, Cuneo, Italy, 2 Anesthesiology and Intensive Care Unit, ASLCN1, Cuneo, Italy, 3 Center for Experimental Medical Research (CeRMS), University of Torino, Italy, 4 Nephrology and Dialysis Unit, "Santa Croce e Carle" Hospital, Cuneo, Italy, 5 Nephrology, Dialysis and Kidney Transplantation Unit, University of Eastern Piedmont "A.Avogadro", "Maggiore della Carità" University Hospital, Novara, Italy AKI is one of the most common complications in patients (pts) admitted to ICU leading to an increased risk of multiple organ failure (MOF) and death. We report a 15-year retrospective analysis of AKI incidence in 2 104

106 different hospitals in the Piedmont region in Italy with the aim to evaluate the clinical impact of AKI on outcome and progression toward chronic kidney disease (CKD). In addition, we analyzed the evolution of RRT modality in our centers. We analyzed all pts admitted to ICU and treated by renal replacement therapies (RRT) for AKI in the period RIFLE, SOFA and ATN_ISS scores were calculated. Diagnosis of sepsis/septic shock was performed according to published criteria. We evaluated ICU mortality and renal function in survivors at ICU discharge. Statistical analysis was performed using the Hemer-Lemeshow test. We treated by RRT 2836 pts for a total of RRT sessions performed. Pts characteristics were: 68.9% males; age 68.2±12.3 years; serum creatinine (scr) at the start of RRT 4.3±2.2 mg/dl; RIFLE Failure 62.5%, Injury 28.5%, Risk 9%; SOFA 10.3±1.2; number of organ failures: 3.7±1.4; ATN_ISS 0.825± ICU mortality was 1560/2836 (55%): the observed mortality was significantly lower than that expected by the ATN_ISS score (61.5%). Sepsis (31.4%) and ischemia-reperfusion injury after major cardiac surgery (24.6%) were the main causes of AKI. Mortality in septic pts (64.3%) was significantly higher than in the non-septic AKI population (45.7%) (p<0.05). At ICU discharge, survivors presented elevated levels of scr (2.4±0.9 mg/dl). In the period , prolonged intermittent RRT was the preferred modality of treatment. In the last 3 years, hemodynamic instability associated with intense fluid overload lead to an increased use of CRRT with regional citrate anticoagulation. Since sepsis is the main cause of AKI associated with a worse outcome, the use of high cut-off or adsorptive membranes was also increased. In conclusion, this 15-year retrospective analysis showed a persistent increase of AKI incidence in ICU usually in association with MOF and high mortality rates. Sepsis was the main cause of AKI and represented a further risk factor for a worse outcome. Since 2013, CRRT using citrate anticoagulation was the preferred modality in consideration of the clinical complexity of these patients. Survivors presented high levels of scr, suggesting the potential progression toward CKD and the need of nephrological follow-up. 19 Acute Kidney Injury In Non Renal Solid Organ Transplantation: a rising clinical problem Vincenzo Cantaluppi 1, Alessandro D Quercia 2, Marita Marengo 3, Sergio Dellepiane 2, Luigi Biancone 2 1 University of Eastern Piedmont, 2 University of Torino, 3 ASLCN1 Cuneo Only few studies evaluated Acute Kidney Injury (AKI) incidence in non renal solid organ transplant (NRSOT) recipients. The aims of the present study were: 1) a 15-year analysis of AKI incidence in NRSOT in a 1000-bed University Hospital; 2) to identify the clinical impact of AKI on outcome and progression toward chronic kidney disease (CKD) in this selected population. We retrospectively analyzed ( ) the percentage of NRSOT in the whole AKI population treated by renal replacement therapies (RRT) in our centre. For each NRSOT recipient, we evaluated RIFLE and SOFA scores and the severity index ATN_ISS at the start of RRT. The percentage of AKI requiring dialysis in the whole NRSOT population and for single transplanted organ (liver, heart or lung graft) was also studied. Renal function was evaluated at the end of the observation period (30 days). Hemer-Lemeshow statistical test was performed. In the period , we treated 2756 critically ill patients with AKI for a total of RRT sessions performed. Among this population, 402/2756 (14.6%) were NRSOT recipients. We treated by RRT 10.8 % of all patients subjected to liver transplantation, 27.5% of heart transplanted patients and 26.2% of lung transplanted patients. Baseline characteristics were: age 59.2 yrs (SD 7.6), male gender 62.5%, serum creatinine 3.76 mg/dl (SD 1.34), number of organ failures 3.7 (SD 1.87) and ATN_ISS score 0.68 (SD 0.16). The 105

107 prevalent cause of AKI in NRSOT patients was sepsis (52.5%), associated with high mortality, multiple organ failures and a difficult management of the immunosuppressive therapy. Overall mortality in NRSOT patients was 42.6% and in particular 38.5% for liver, 48% for heart and 41.5% for lung transplant recipients, respectively. Mean serum creatinine at the end of the study period (ICU or hospital discharge) was 2, 43 mg/dl (2.06 mg/dl in liver, 2.42 mg/dl in heart and 2.82 mg/dl in lung graft recipients, respectively). In conclusion, we observed a continuous increase of AKI incidence in the NRSOT population. The main cause of AKI was severe sepsis which was associated with an increase of mortality and with an impairment of renal function that may be responsible for the progression toward CKD in survivors. Early goal-directed therapies to inhibit AKI may potentially improve outcome and limit progression toward CKD in NRSOT recipients. 20 The Effect of the Choice of Contrast Media on Renal Failure Events in Inpatient Cardiovascular Procedures Peter J Mallow 1, Meridith Johnson 2, Lauren Lim 2, Guy David 3 1 CTI Clinical Trial and Consulting, 2 GE Healthcare, 3 University of Pennsylvania PURPOSE OF STUDY: The physiochemical properties of iodinated contrast media (CM) may increase the likelihood of renal failure, which may lead to a significant increase in morbidity, mortality, and cost associated with the procedure. The objective of this study was to assess the relationship between iso-osmolar CM and lowosmolar CM (LOCMs), and renal failure events in patients undergoing inpatient cardiovascular procedures. METHODS: The Premier Hospital database was used to identify patients between January 2008 and September Eligible patients had a primary cardiovascular procedure (interventional or diagnostic) defined by International Classification of Diseases, 9th Revision (ICD-9) and/or Current Procedural Terminology (CPT ) codes, inpatient admission, and LOCM or iso-osmolar CM agent. CM agents were identified by Standard Charge Master codes and text mining algorithms. One iso-osmolar CM, iodixanol, was identified. Six LOCMs were identified: iohexol, ioversol, iopamidol, ioxaglate, ioxilan, and iopromide. Renal failure during the visit was determined by ICD-9 diagnosis codes. Multivariable regression analysis was conducted using Ordinary Least Square (OLS) and hospital fixed-effects specification to assess the relationship between renal failure and CM use. RESULTS: A total of 662,299 cardiovascular procedure visits met the inclusion criteria. Patients receiving isoosmolar CM comprised 29% of the visits. In 74% of the hospitals identified, both iso-osmolar CM and LOCM was used. Iso-osmolar CM was used in older patients (66.7 vs. 62.8; p < ) compared to LOCM. Patients receiving iso-osmolar CM were generally sicker as measured by Charlson Comorbidity Index Score compared to patients receiving LOCM (3.9 vs. 3.3; p < ). Univariate OLS analysis indicated that patients receiving iso-osmolar CM had 1.9% (p < 0.01) more renal failure events during the visit compared to patients receiving a LOCM. Controlling for unobserved heterogeneity across hospitals using a hospital fixed-effect specification, we found 2.3% (p < 0.01) fewer renal failure events with iso-osmolar CM. This absolute difference represents an approximately 55% relative difference from the 4.2% rate for the overall population. CONCLUSION: In this retrospective study, the use of iso-osmolar CM was associated with fewer renal failure events compared to LOCMs in patients who underwent inpatient cardiovascular procedures. This may translate to reduced hospital costs. 106

108 21 Change of Estimated Glomerular Filtration Rate to Assess the Extent of Renal Recovery after Cardiac Surgery Associated Acute Kidney Injury Jiarui Xu 1, Bo Shen 1, Jun Jiang 2, Yi Fang 1, Yi mei 1, Zhonghua Liu 1, Jianzhou Zou 1, Chunsheng Wang 3, Xiaoqiang Ding 1, Jie Teng 1 1 Department of Nephrology,Zhongshan Hospital, 2 Department of Nephrology, Anhui Provincial Hospital, Hefei, China, 3 Department of Cardiovascular Surgery, Zhongshan Hospital, Shanghai , China Objective: The extent of renal recovery after acute kidney injury (AKI) is often assessed by change of serum creatinine post- and pre-operation. Our study tried to find out if the change of estimated glomerular filtration rate (egfr) can do the assessment more accurate and the relationship between different extent of egfr decrease and longterm outcome of the AKI patients. Methods: We collected data of patients who underwent cardiac surgery from April 2009 to December Complete renal recovery was defined as SCr concentrations at discharge 44 mmol/l above baseline values. The egfr was determined according to the simplified MDRD formula. The 2 years primary endpoint was all-cause of mortality and secondary endpoint was progressive CKD(CKD stages 4 5 including ESRD). Results: Among the total of 3245 patients enrolled, the AKI incidence was 39.9% (n=1295). According to SCr criteria, there are 72.9% (n=944) patients had completely renal recovery. Using the simplified MDRD formula to calculate the egfr before and after AKI patients who was assessed as complete renal recovery by SCr criteria, the egfr after AKI was significantly lower than before AKI (88.9± 33.6 vs 94.5±29.7 ml/min/1.83m2,p<0.001). According to simplified MDRD formula, there are 33.7% (n=436) patients with egrf 90ml/min/1.73m2 and 66.3% (n=859) patients with egrf<90ml/min/1.73m2 at discharge. After 2 year period followed up, we first analyze the outcomes of AKI patients with complete renal recovery assessed by SCr criteria. Cox proportional hazards regression model showed that AKI with completely renal recovery is still the risk factor for accumulated overall survival (RR 1.79, 95%CI 1.28 to 2.52) and progressive CKD (RR 1.92, 95%CI 1.37 to 2.69). Then we analyze the outcomes of AKI patients whose extent of renal recovery assessed by egfr criteria. Cox proportional hazards regression model showed that AKI patients with egrf < 90ml/min/1.73m2 at discharge is the risk factor for accumulated overall survival (RR 3.7, 95%CI 2.66 ~ 5.16;) and progressive CKD (RR 5.28, 95%CI 3.86 ~ 7.21). But AKI patients with egrf 90ml/min/1.73m2 at discharge is not the risk factor for accumulated overall survival and progressive CKD. Conclusions: The change of SCr criteria may over-estimate the extent of renal recovery of CSA-AKI patients.csa-aki patients with egrf(simplified MDRD formula) 90ml/min/1.73m2 at discharge can be the clinical criteria for completely renal recovery. 107

109 22 Effect of Body Mass Index on Acute Kidney Injury after Cardiac Surgery Zhouping Zou 1, Jiarui Xu 1, Yi Fang 1, Jianzhou Zou 1, Xiaoqiang Ding 1, Jie Teng 1 1 Department of Nephrology,Zhongshan Hospital Objective :Among maintenance hemodialysis patients, the higher body mass index(bmi) was, the higher survival rate was. This study was to explore the relationship between BMI and incidence, mortality of AKI and AKI requiring RRT (AKI-RRT) after cardiac surgery. Methods :Clinical data of patients undergoing cardiac surgery, which included demographic data of preoperative intraoperative postoperative, were prospectively collected in Zhongshan hospital affiliated Fudan University from January 2009 to December According to BMI classification for Chinese: low weight group (BMI>18.5kg/m2), normal weight group (18.5 BMI<24kg/m2), overweight group (BMI<28kg/m2), obese group (BMI 28 kg/m2 ). Results: A total of 8013 patients enrolled, including 4477 males and 3536 females with the mean age of 53.1±14.0years. The overall AKI incidence was 34.0%(n=2723). The hospital mortality of AKI was 5.7%(n=156). The incidence of AKI-RRT was 4.9%(n=133). The morality of AKI-RRT was 58.6%(n=78).The incidences of AKI in low weight group, normal weight group, overweight group, obese group were 27.8%,31.4%,35.7%,45.0% (P<0.001). The hospital mortality of AKI in four groups were 9.0%,6.5%,4.6%,5.0%,there was no significantly statistical difference (P =0.062). The hospital mortality of AKI-RRT in four groups were 62.5% 61.3% 51% 75%,also no significantly statistical difference (P =0.426). Conclusion: BMI is an independent risk factor for AKI after cardiac surgery, the AKI incidence increased, as BMI gained. The hospital prognosis of AKI and AKI-RRT were optimum, when BMI was kg/m2. 23 Early Diagnosis of Severe Sepsis and Acute Kidney Injury, Judgment of Rapid Transport to Critical Care Center: Better Prognostic Factor Hisashi Imahase 1, Yuichiro Sakamoto 1, Kosuke C Yamada 1, Mayuko Yahata 1, Hiroyuki Koami 1, Miho Ohta 1, Ryota Sakurai 1, Toru Miike 1, Ryo Fujita 2, Satoshi Inoue 1 1 Saga University Hospital, Saga city, Saga, Japan, 2 Karatsu Red Cross Hospital, Karatsu city, Saga, Japan Purpose of the study The prognosis of patients with severe sepsis or septic shock is improving. In our center, although promoting the standardization and individualization of sepsis treatment, some patients die. We examined whether acute kidney injury affects the prognosis of septic patients. Methods We included the patients with severe sepsis and septic shock who admitted from the emergency department to the ICU from Jan to Jun We defined severe sepsis as patients with SOFA score 2 points worse than sepsis onset before. Gender, age, APACHE2, SOFA, KDIGO classification of AKI, time from sepsis onset to 108

110 our center visits, and time from sepsis onset to the first antibiotic administration, were examined. Results The number of patients was 60: non-survivor 18(30%), and survivor 42(70%). As APACHE2, SOFA and KDIGO classification of AKI was bad, life prognosis was bad. The table showed the relationship between KDIGO classification and the prognosis. As the definitive treatment or the first antibiotic administration was earlier, KDIGO classification of AKI and life prognosis was better. Conclusion The early diagnosis of severe sepsis and acute kidney injury and the judgment of rapid transport to critical care center were better prognostic factor. KDIGO classification Non-survive Survive Mortality (%) Non-AKI Hemodialysis Patients Total Changes of Epidemiology and Influencing Factors of Acute Kidney Injury After Cardiac Surgery- A Five year Study from 2009 to 2013 Zhouping Zou 1, Jiarui Xu 1, Yi Fang 1, Jianzhou Zou 1, Xiaoqiang Ding 1, Jie Teng 1 1 Department of Nephrology,Zhongshan Hospital Objective :We collected the epidemiological data of patients with AKI from 2009 to 2013 in order to explore the influencing factors of changes of epidemiology after cardiac sugery. Methods: Clinical data, which included demographic data of preoperative, intraoperative, postoperative, were prospectively collected in our hospital from January 2009 to December The main endpoint was poor prognosis including overall mortality and abandon of treatment. The second point was renal outcome. Results :A total of patients enrolled, including 6637 males and 5056 females. The overall AKI incidence was 34.5%. The AKI incidence increased during the five years from 34.2% to 36.5% (P<0.05).There was no significantly statistical differences in AKI-RRT incidences during the five years (p=0.360); The hospital mortality of AKI decreased from 6.3% in 2009 to 3.8% in 2013.The incidence of poor prognosis in AKI were 8.3%,7.5%,6.8%,5.1%,8.0% (P=0.196).The mortality of AKI-RRT decreased from 47.1% in 2009 to 29.5% in 2013 (P= 0.230). The incidence of poor prognosis in RRT decreased from 66.7% to 57.4% (P=0.825). Multivariate logistic regression analysis showed that male, old age, body mass index(every additional 5 kg/m2 ),hypertension, chronic heart failure, pre-operative serum creatinine>115µmol/l,cpb(every additional 30min )were the risk factors of AKI after cardiac surgery. Conclusion: The incidence of AKI after cardiac surgery increased from 2009 to 2013 and the rate of poor prognosis did not change. 109

111 25 Positive Fluid Balance as a Predictor of ICU Free Days in Patients with Kidney Disease Requiring Dialysis sharad patel 1, Hernan Rincon-choles 1, Tarik Hanane 1, Duncan Hite 1, Sevag Demirjian 1 1 cleveland clinic Positive fluid balance as a predictor of ICU Free Days in patients with kidney disease requiring dialysis Sharad Patel, Hernan Rincon-Choles, Tarik Hanane, Duncan Hite, Sevag Demirjian Department of Critical Care Medicine, Department of Nephrology and Hypertension, Cleveland Clinic Background: Optimal fluid management in critically ill patients has recently come under scrutiny due to volume driven morbidity such pulmonary edema, intra-abdominal hypertension, renal venous pressures, and bowel edema. The latter is further compounded by renal impairment, prevalent in these patients. Our aim in this study was to assess volume burden on ICU-free days in patients with renal failure. Methods: We retrospectively studied adult critically ill patients with renal failure requiring renal replacement therapy (RRT) between the years 2011 and We examined the effect of 7-day ICU cumulative fluid balance on ICU-free 28-days using linear regression. Results: The cohort included 1328 subjects with renal failure requiring RRT: 841 with AKI, and 487 with ESRD. The median age was 63 (54,71), 69% were white, and 56% male. Median cumulative fluid balance at one week was 3,315 ml (range -1,078 to 7,730 ml). Univariate analysis of the effect of fluid balance on the outcome showed a curvilinear shape (p<.001, nonlinearity p <.001). Conclusion In patients with renal failure requiring RRT, positive fluid balances is associated with reduced ICU-free days. The association is non-linear in nature, and dose-dependent with increasing fluid balance. Further research should incorporate adjustment of severity of illness which may confound the observed association. 110

112 26 Clinical Significance Of Renal Biopsy In AKI SANTOSH HEDAU 1, RAJASEKARA CHAKRAVARTHI 1, VIJAYA TAURANI 1 1 CARE HOSPITAL PURPOSE OF STUDY Renal biopsy in AKI helps us to diagnose, effectively treat and prognosticate patients based on histopathology. The renal biopsy confirms clinical diagnosis on many occasions and helps in precise treatment. METHOD USED We did retrospective analysis of renal biopsy data at our institute from January 2003 to September Total 3293 renal biopsy were done during this period. the indication of biopsy was AKI in 759 patients out of 3293 biopsies. This cohort of AKI was separated and analysed based on histopathology findings. SUMMARY OF RESULTS The commonest histopathological lesion was acute interstitial nephritis (AIN) in 28.5% patients (n=216). Proliferative glomerulonephritis (PIGN and DPGN) was found in 17.8% (n=135). Acute tubular necrosis (ATN) was found in 14.1% (n=107) as third most common lesion. The other findings included cresenteric glomerulonephritis in 9.7% (n=74), vasculitis in 6.9% (n=53). Cortical necrosis and myeloma was found in 1.05% and 1.5% respectively. Patients with diabetic nephropathy were analysed separately. AIN with background diabetic nephropathy was seen in 13.7% (n=104). Hence the commonest lesion was AIN in 42.2% patients. CONCLUSION It is important to biopsy patients with AKI to know histopathology. The commonest lesion found was AIN which is potentially treatable and can avoid rapid loss of renal function if treated in time. This is in contrary to present understanding where ATN is presumed to be the commonest lesion. It looks justified in doing renal biopsy for diabetic patients with AKI. The treatment of potentially treatable lesions which are often missed helps in preventing decline of renal parameters to ESRD. 111

113 27 Acute Kidney Injury Recovery and the Risk of Chronic Kidney Disease in Sepsis Survivors Javier A Neyra 1, Xilong Li 1, Beverley Adams-Huet 1, Orson W Moe 1, Robert D Toto 1 1 University of Texas Southwestern Medical Center Background: AKI is a frequent complication of sepsis and is associated with an increased risk for subsequent CKD. The purpose of this study was to investigate whether the absence of 90-day AKI recovery increases the risk of CKD in sepsis survivors. Methods: We conducted a retrospective cohort study of patients admitted to the ICU with a diagnosis of severe sepsis or septic shock from May 2007 to December We excluded patients with egfr <15 or receiving chronic dialysis prior to enrollment. Baseline serum creatinine (SCr) was defined as the most recent SCr within the 3-month period before ICU admission. The highest SCr during ICU admission was used to diagnose AKI (KDIGO criteria). The independent variable, AKI recovery, was determined by the ratio of 90-day postdischarge SCr / baseline SCr in RRT-free survivors: <1.1 indicated AKI recovery and 1.1 no AKI recovery. The primary outcome measure was incident or progressive CKD based on relative or absolute egfr changes during the follow-up period. A Cox proportional hazard regression analysis adjusting for age, baseline egfr, diabetes, AKI severity, SOFA score, and the need for acute RRT was performed. Results: Of 6268 ICU patients included in the study, 3703 (59%) suffered from AKI and 729 (12%) required acute RRT. A total of 4949 (79%) patients survived the hospitalization. Of these, we identified 2401 sepsis survivors that were RRT-free at 90 days following hospital discharge and had available follow-up data. Incident or progressive CKD occurred in 399 (32%) of patients that suffered from AKI (47% in those without AKI recovery and 18% in those with AKI recovery) and in 124 (11%) of patients that did not suffer from AKI, median follow-up 2.5 years. 90-day AKI recovery status was an independent predictor of CKD (adjusted HR 4.04, 95% CI for absent AKI recovery vs no AKI; 1.59, for AKI recovery vs no AKI; and 2.54, for absent vs AKI recovery). Other independent predictors of CKD post-aki were older age, lower baseline egfr, the need for acute RRT, and higher admission SOFA score. Conclusions: The absence of AKI recovery within 90 days following hospital discharge is a strong and independent predictor of CKD in sepsis survivors. The timely evaluation of AKI recovery may serve to riskstratify sepsis survivors and implement more vigilant surveillance for CKD in this susceptible population. 112

114 28 Post-Operative Acute Kidney Injury After Major Non-Cardiac Surgery and its Association with Death in the Following Year Michael E O'Connor 1, Russell W Hewson 1, Christopher J Kirwan 1, Rupert M Pearse 2, John R Prowle 2, 2 William Harvey Research Institute, Queen Mary University of London Background: Acute kidney injury is a common complication after major surgery that has been associated with adverse outcomes. Method: We performed a retrospective cohort study of major non-cardiac surgery in a teaching hospital over an eighteen-month period, examining the incidence of AKI and relationship with post-operative outcomes over one-year follow up. AKI was defined by KDIGO creatinine criteria. Major surgery was defined as inpatient procedures of >1h duration. End stage real disease and those without pre or post-operative creatinine measurement were excluded. To assess the independent effect of AKI on survival, a multi-variable Cox proportional-hazard survival model was developed examining survival from 7 to 365 days after surgery. Results: 1897 patients were included in our final analysis, post-operative AKI occurred in 128 patients (6.8%), of these 101 had KDIGO stage 1 (5.4%), 19 KDIGO stage 2 (1%) and 8 KDIGO stage 3 (0.4%). Patients who developed AKI were significantly older, had a lower baseline egfr, were in a higher ASA class and spent longer in hospital post-operatively compared to those patients who did not develop AKI. Hospital Mortality occurred in 17/128 (13.3%) of patients that developed AKI post-operatively compared to only 16/1741 (0.9%) of those that did not (p<0.001). However, by one year after surgery 34/94 (27%) of patients who developed post-operative AKI had died compared to only 106/1741 (6%) who had not had AKI (Fig1), p< In the multi-variable model accounting for multiple confounders AKI was associated with a hazard ratio for death of 3.0 ( ) in the year after surgery. Importantly AKI defined by only a 26µmol/L creatinine rise and AKI with recovery remained associated with on-going increased risk of death to one year. Conclusions: In a well-characterised population of patients undergoing major surgery we have demonstrated a strong association between even mild post-operative acute kidney injury and increased risk of death in the next year. 113

115 29 Trajectory of Serum Creatinine after Major Surgery and Relationship with Acute Kidney Injury Michael E O'Connor 1, Russell W Hewson 1, Christopher J Kirwan 1, Rupert M Pearse 2, John R Prowle 2 1 Adult Critical Care Unit, The Royal London Hospital, 2 William Harvey Research Institute, Queen Mary University of London Background: We have demonstrated that even mild and transient perioperative acute kidney injury is associated with significantly worse survival in the year after major surgery (see accompanying abstract). However, confounding effects of major illness on serum creatinine levels may cause severity of AKI to be underestimated and recovery from AKI over-estimated (1). Methods: From a population of 1897 patients undergoing major surgery (of which 128 had peri-operative AKI) we examined baseline and hospital discharge estimated GFR (CKDEpi creatinine formula) and the trajectory of serum creatinine in patients who were hospitalized for 5 days after surgery. Results: In 1836 patients who survived to hospital discharge median duration of hospitalization was 7 days (IQR: 4-11) overall and 11 days (6-25) in patients who had peri-operative AKI. In all hospital survivors mean egfr rose significantly from baseline to discharge: 88.4 to 94.7ml/min/1.73m2 (p<0.001). However in those with AKI discharge egfr was similar to baseline 76.4 to 74.5 (p=0.6) patients stayed 5 days after surgery, in those with AKI mean creatinine rose rapidly and eventually settled to near baseline, however in all patients creatinine fell progressively in the five days after surgery and was ~10% below baseline at discharge (Figure). In a regression analysis a higher discharge egfr significantly correlated with longer hospital length of stay (p<0.001), however no such relationship existed for baseline egfr (p=0.79). Conclusion: Underlying reduction in serum creatinine after major surgery may confound our ability to identify AKI and to assess its severity and recovery. Importantly, these effects may be more pronounced in patients with longer hospital admissions who are at higher risk of complications including AKI. Figure Legend Figure: Trajectory of serum creatinine in 1225 patients with post-operative length of stay of 5 or more days who survived to hospital discharge. Mean with SEM. Ref 1) Prowle et al Clin J Am Soc Nephrol 9:

116 30 Effect of Renin Angiotensin Blockade on Renal Function at Short and Mid Term in Patients Undergoing Coronary Angiography EMMANUEL VILLALOBOS 1, ARMANDO VAZQUEZ 1 1 Instituto Nacional de Cardiología Ignacio Chavez INTRODUCTION: The use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on short-term renal function after contrast medium is still controversial; moreover, its impact on mid-term renal function in populations with proven cardiovascular benefit has not been studied. METHODS: A retrospective cohort of patients undergoing coronary angiography in a third-level academic reference center in Mexico City from January 1st to December 31st The clinical and biochemical characteristics were obtained from medical records, including a 3 year follow-up after coronary angiography. Specifically, the use of ACEI/ARB peri-procedure and during follow-up was assessed. RESULTS: A total of 353 pts were analyzed, 283 (80.2%) were male, aged 58.9 ± 12.1 years, 164 (46.4%) were diabetic, 189 (53.5%) had hypertension, 331 (93.8%) had acute coronary syndrome, 42 (11.9%) had preexisting chronic kidney disease (CKD). A total of 106 pts received ACEI/ARB (30%) prior to catheterization and 285 (80.7%) during follow-up. The overall incidence of contrast-induced nephropathy (CIN) was 13.3% (47/353), with a significant reduction in pts with ACEI/ARB (28 of 277 [10.1%] vs 19 of 76 [24.7 %], p<0.01). This short-term protective effect remained in pts with anemia, diabetes, CKD and/or previous use of ACEI/ARB, although no difference was observed in pts with NYHA functional class III-IV, and a higher incidence of CIN was shown in pts with mean arterial pressure (MAP) <85 mmhg in presence of ACEI/ARB. In multivariate analysis by Cox proportional risk for progression to CKD up to 3 years of follow-up, the use of ACEI/ARB showed a HR 1.41 (95% CI, , p=0.116). The change in glomerular filtration rate over time was ( to ) ml/min/month with ACEI/ARB vs ( to 0.125) ml/min/month without ACEI/ARB (p=0.177). CONCLUSIONS: The use of ACEI/ARB peri-catheterization showed a decrease in the incidence of CIN in our population, except for patients with MAP <85 mmhg. Up to 3 years of follow-up, ACEI/ARB showed no deleterious effect in progression to CKD. A randomized controlled trial is warranted. 97 (number out of sequence) Risk factors for acute kidney injury and mortality after orthotopic liver transplantation Chen XiaoHong, Chen Nan, Wang ting, Xu jiarui, Teng Jie, Ding XiaoQiang Blood Purification Center, Zhongshan Hospital of Fudan University, Department of Liver surgey, Zhongshan Hospital of Fudan University ICU,Shanghai public health clinical center Purpose: The aim of this study is to identify the risk factors for acute kidney injury (AKI) classified according to AKI network criteria, and mortality after orthotopic liver transplantation (OLT). METHODS: From January 2001 to October 2010, patients undergoing OLT were retrospectively included in the study. Risk factors for AKI and death were investigated. 115

117 RESULTS: A total 809 patients were included, with median age of 50 years. AKI was found in 265 (32.75%) patients in the first 7 days after OLT. Risk factors for AKI were: age (OR=1.02, 95% CI: 1.00, 1.04), low-blood pressure during operation (OR=1.78, 95% CI: 1.63, 1.95) and pre-egfr (OR 1.02, 95%CI: 1.02, 1.03). The mortality was 9.43%. AKI was an independent risk factor for 30-day mortality after OLT (OR=0.001, 95% CI: 1.24, 2.30). Low-Blood pressure during operation was a predictor for hemodialysis need (OR=1.42, 95%CI 1.26, 1.59). Of the 265 post-olt AKI patients, 22 did not recover renal function within 1 year. CONCLUSIONS: AKI after OLT is not an uncommon complication and associated with a poor clinical outcome. Age, low-blood pressure during operation and pre-egfr are risk factors for post-olt AKI. AKI is a risk factor for perioperative death and can lead to prolonged renal function impairment after OLT. Low-Blood pressure during operation is a predictor for hemodialysis need. 116

118 RESEARCH IN AKI 31 Incidence and Risk Factors of Acute Kidney Injury Following Transcatheter Aortic Valve Replacement Wisit Cheungpasitporn 1, Charat Thongprayoon 1, Narat Srivali 1, Wonngarm Kittanamongkolchai 1, Kevin L Greason 1, Kianoush B Kashani 1 1 Mayo Clinic, Rochester, MN, USA Background: This study aimed to determine the incidence and risk factors of Acute Kidney Injury (AKI) following Transcatheter Aortic Valve Replacement (TAVR). Methods: We included all adult patients undergoing TAVR for aortic stenosis from January 1, 2008 through June 30, 2014 at a tertiary referral hospital. AKI was defined based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. We performed a multivariate logistic regression to identify factors associated with post-procedural AKI occurrence. Results: Three hundred eighty-six patients met the inclusion criteria, of which 106 (28%) developed AKI. In multivariate analysis, AKI development was independently associated with a transapical approach (OR, 2.81; 95% CI, compared with transfemoral approach), and the need for an intra-aortic balloon pump (OR, 9.11; 95% CI, ) [Table 1]. Higher baseline renal function (OR, 0.77 per 10ml/min/1.73m2 increment in glomerular filtration rate; 95% CI, ) was significantly associated with a decreased risk of AKI. Patients who developed AKI had significantly higher in-hospital mortality than patients without AKI (6.6% vs 1.4%, respectively; P=.01). Conclusion: In a cohort of patients undergoing TAVR for aortic stenosis, AKI commonly occurred and was significantly associated with increased mortality. Baseline renal function, procedure approach, and the need for circulatory support were important predictive factors for post-procedural AKI occurrence. Variables Odds Ratio (95% CI) GFR (per 10mL/min/1.73m2) 0.78 ( ) <0.001 Arterial approach Transfemoral 1 (ref) - Transapical 2.81 ( ) <0.001 Transaortic 1.54 ( ) 0.45 Intra-aortic balloon pump 9.11 ( )

119 32 Proteomics of AKI induced by Maleic Acid on renal tubule cells Hugo Y Lin 1, Shih-Shin Liagn 2 1 Kaoshiung Medical University Hospital, 2 Department of Biotechnology, College of Life Science, Kaohsiung Medical University Purpose of the study: Maleic acid (MA) was used in the manufacturing process in order to augment the productivity of preparing the conventional comestible starch foodstuffs in Taiwan. At the same time, in the process of manufacturing to add the malic anhydride which is the hydrolyzed form of maleic acid. Thus, the maleic anhydride will interact with water and invert maleic acid, and simultaneously, maleic acid integrates into the foods. Nevertheless, the critical thing is that the human being could eat the food which may have envenomed. Up to present, there are plenty of food additives; the most common used to increase a great number of decent traditional foods is furan-2, 5-dione (Maleic anhydride) which is the acid hydride of maleic acid, and in other words, it is an archetypal product from hydrolyzing maleic anhydride. On top of that, when the food additives, maleic anhydride, degrade in the processing, maleic acid in the products will be released. Furthermore, depending on Fanconi's syndrome, maleic acid could similar stimulate a speedy, reversible, elaborate dysfunction in the renal tubule Methods used: The silicon dioxides (SiO2) particles will sediment to a silanized linker (3-aminopropyl triethoxyslane, APTES), and moreover, the maleic acid and APTES!SiO2 fabricate to the maleate chemical probes. Summary of the results: The probe can be used to detect the target proteins of maleate in this study and demonstrate the protein-protein interactions which are associated maleic acid. We expect that synthetic maleic acid chemical probes incubated the cell lysates of normal human kidney (HK-2) cell lines, and establish the relationships between maleic acid and HK-2 cells for protein-protein interaction analysis. Conclusion reached: By means of STITCH database networks software in order to understand the relationship between maleic acid chemical probes and HK-2 cells whether they were protein!protein association and specific binding or not. Judging by D/H ratios <1.8, we could remove the most possible non-specific proteins by using the method. 118

120 33 Analysis of hypo and hyperphosphatemia in an ICU cohort Marcus Broman 1, Amanda Wilsson 1, Bengt Klarin 1 1 Skane University Hospital Purpose of the study The aim was to evaluate the epidemiology of phosphate disturbances and their adjusted morbidity and mortality. Methods used 5337 patients were screened, 681 were excluded, resulting in a final cohort of 4656 patients, divided in a control group (0.7<phosphate<phosphate<phosphate2.5 mm) and a mixed group (phosphate<0.7 AND >1.5 mm), as shown in Figure 1. Summary of the results The distribution of phosphate values was; measurements, mean 1.18 mm, SD ±0,52, min 0,04 and max 6,1 (Figure 1). Kaplan-Meier survival curves were plotted over 180 days. Mean survival days were 177 days in moderate hypo, 141 in severe hypo and 114 in moderate hyper, 47 in severe hyper and 112 in the mixed group, compared to 179 days in the control group. A COX proportional hazards pairwise equation was used to calculate hazard ratios (Table 1). Severe hyper was the only study group showing significantly increased hazard ratio p< Moderate hyper showed a tendency towards increased hazard ratio p= Study groups in the hypophosphatemic arm did not show significantly increased hazard ratios, neither did the mixed group. 13/38 covariates in the hyperphosphatemic arm compared to 9/39 in the hypophosphatemic arm showed increased hazard ratios. The mixed group showed significantly longer ventilator treatment time compared to all other groups; 177,25 hours to 25,82 in the control group and to 77,27 in moderate hypo and to 109,60 in severe hypo and to 76,35 in moderate hyper and to 86,42 in severe hyper, p< /4656 (5,0 %) patients got CRRT and only 9 were in the control group meaning that 96,1 % of the CRRT patients showed a phosphate deviation. Hyperphosphatemia could exert its action through chelating calcium and thus causing hypocalcemia. Regression analysis showed that there were no correlation between phosphate and simultaneous ionized calcium values; pearson coefficients were 0,039 for minimum and -0,051 for maximum phosphate. Reached conclusions Hypophosphatemia in absence of organ failure seems not to increase mortality. Increasing level of hyperphosphatemia is connected to worse outcome and COX analysis indicated that organ system failure may be the main reason.</phosphate Table and figure on following pages 119

121 number of patients in group studygroup compared to control age additional year gender female SOFA score total SOFA score renal diagnosis circulatory severe hypo moderate hypo control moderate hyper severe hyper ,734 p=0,2192 1,035 p<0,0001 0,966 p=0,7441 1,214 p<0,0001 1,215 p<0,0001 4,961 p=0,1118 0,912 p=0,322 1,035 p<0,0001 1,025 p=0,7814 1,201 p<0,0001 1,179 p<0,0001 2,915 p=0,1342 diagnosis coagulation 0 p=0, p=0,9878 diagnosis diabetes diagnosis fluid balance diagnosis GI tract diagnosis infectious 0 p=0,9819 1,121 p=0,9357 5,328 p=0,0988 3,567 p=0,2099 diagnosis intoxication 0,446 p=0,5692 diagnosis multiple trauma diagnosis neoplasm diagnosis neurological diagnosis neursurgical 1,269 p=0,5105 2,2 p=0,0218 3,075 p=0,2750 2,99 p=0,2823 3,227 p=0,2575 7,575 p=0,046 1,3 p=0,4595 2,52 p=0,0042 2,347 p=0,4877 0,416 p=0,4747 3,065 p=0,1201 2,855 p=0,1441 0,581 p=0,5882 2,313 p=0,2518 2,25 p=0,2619 2,475 p=0,2191 5,928 p=0,013 1,065 p=0,8879 diagnosis pulmonare 2,252 p= p=0, p=0, p=0,9513 1,168 p=0,0656 1,032 p<0,0001 1,639 p<0,0001 1,032 p<0,0001 1,02 p=0,7954 1,072 p=0,4384 1,196 p<0,0001 1,156 p<0,0001 1,853 p=0,0712 1,689 p=0,6189 0,889 p=0,8801 1,131 p=0,8260 2,084 p=0,0369 1,363 p=0,3767 0,122 p=0,0469 1,125 p=0,7616 1,303 p=0,4665 1,257 p=0,5570 1,196 p<0,0001 1,138 p=0,0015 2,126 p=0,017 1,291 p=0,8071 0,694 p=0,7269 1,205 p=0,0813 2,241 p=0,0161 1,539 p=0,1912 0,169 p=0,0906 1,267 p=0,5336 1,321 p=0,4246 1,067 p=0,8705 3,03 p=0,0025 2,968 p=0,0022 6,538 p=0,0628 diagnosis obstretric diagnosis other 4,603 p=0,03 mixed hypo/hyper 0,812 p=0,0741 1,036 p<0,0001 0,904 p=0,2536 1,189 p<0,0001 1,201 p<0,0001 1,841 p=0, p=0,9823 0,884 p=0,881 0,301 p=0,2666 1,738 p=0,1989 1,231 p=0,6282 0,144 p=0,7624 1,091 p=0,8223 1,142 p=0,7624 1,143 p=0,7818 3,355 p=0, p=0, p=0,9678 3,04 p=0,2782 2,643 p=0,

122 34 Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN): Design of a Retrospective Cohort Study Jennifer G Jetton 1, Jennifer R Charlton 2, Ronnie Guillet 3, David J Askenazi 4 1 University of Iowa Children's Hospital, 2 University of Virginia, Charlottesville, VA, USA, 3 University of Rochester, Rochester, NY, USA, 4 University of Alabama, Birmingham, AL, USA On behalf of the Neonatal Kidney Collaborative Background: Acute kidney injury (AKI) affects 30% of NICU patients. The Neonatal Kidney Collaborative (NKC) is a multidisciplinary, international group of neonatologists and pediatric nephrologists interested in investigating important questions related to neonatal AKI. Objective: To design and establish the infrastructure for a retrospective cohort study (AWAKEN) to: define the epidemiology of neonatal AKI, determine if current categorical definitions of AKI are associated with mortality, length of stay, and discharge serum creatinine, determine how neonatal fluid balance relates to biochemical data and short term outcomes. 121

123 Design/Methods: In 2014, the NKC was established with at least 1 pediatric nephrologist and 1 neonatologist from institutions in 4 countries (USA, Canada, Australia, India). A Steering Committee and 4 subcommittees were created. The database subcommittee oversaw the development of case report forms (CRFs) and the webbased database using MediData Rave housed at Cincinnati Children's Hospital that captured, managed, and reported data for AWAKEN. Individual centers were responsible for entering data on all NICU admissions from 1/1/2014-3/31/2014. Results: The NKC grew from 16 to 24 sites. CRF development took 9 mo, the electronic database build took 10 wk, and pilot testing took 8 wk. All site PIs and research staff completed standardized training. The database includes ~325 unique variables representing >4 million discrete data points. Data entry began 3/15. Each subject required 1-2 h for data extraction and min for data entry. Over 28,000 queries were generated and resolved to date. By 10/1/15, 20 sites completed data entry (3397 subjects screened, 1742 enrolled). Data entry from all sites will be completed by 12/15. Conclusions: AWAKEN is the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during inpatient hospitalization. The time and effort needed to establish the collaborative and develop the database was considerable, but it is anticipated that the AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health and well-being of newborns at risk for kidney disease. 35 Computerized Prediction of AKI Outperforms Plasma NGAL: a Retrospective Analysis Flechet Marine 1, Fabian Güiza 1, Miet Schetz 1, Ilse Vanhorebeek 1, Pieter Wouters 1, Inge Derese 1, Jan Gunst 1, Michael P Casaer 1, Greet Van den Berghe 1, Geert Meyfroidt 1 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium Purpose Critically ill patients at risk for Acute Kidney Injury (AKI) may benefit from early detection of this condition. We aimed to develop and validate accurate prediction models for AKI during the first week of Intensive Care Unit (ICU) stay. Additionally, we aimed to compare the models predictive performance against plasma NGAL (pngal), a well-studied biomarker for early detection of AKI. Methods Retrospective analysis of patient data from the multicenter randomized EPaNIC trial, comparing early versus late supplemental parenteral nutrition in critically ill patients. Data were split into a development (n=2194) and a validation (n=2434) cohort. pngal upon ICU admission was determined in 2274 patients from the validation cohort. We derived and validated 4 multivariate random forest models to predict AKI (defined according to the creatinine-based KDIGO criteria) within the first week of ICU stay. To mimic the availability of patients data in the ICU, models were based on routinely collected patient information available at baseline (model B), ICU admission (model AB), at the end of the first day (model D1AB) and using the first 24 hours of monitoring and medication data (model D1-24hAB). Model performance was assessed using area under the ROC curve (AUC), decision curve analysis, and calibration. Results Table 1 reports the performance of the models in development and validation cohorts, and pngal performance in the validation cohort. Figure 1 specifically shows the decision curves of pngal and model AB in the 122

124 validation cohort. Overall, all models presented good discriminability, net benefit and calibration, which remained after external validation. Model AB achieved a higher discriminability and net benefit than pngal. Predictive performance increased when information from later time points was added. Conclusion Prediction models based on routinely collected patient information accurately identify patients at risk for developing AKI within the first week of ICU stay. Additionally, models developed with information available upon ICU admission outperformed pngal. Whether such in silico model could outperform any biomarker for AKI remains to be investigated. To be of any clinical use, these biomarkers should always demonstrate an added value over routinely collected data. Alternatively, computer models could be used to select those higherrisk patients in whom biomarkers could be of additional value to predict AKI or stratify patients. Development cohort Model B AB D1AB D1-24hAB Validation cohort B AB D1AB D1-24hAB N AKI prevalence AUC Net benefit Calibration slope Calibration in the large pngal

125 36 A Case of Successful Treatment via Continuous Renal Replacement Therapy in Patient with Acute Kidney Injury due to Liver Abscess. JOON SEOK OH 1, YOO JEONG OH 2 1 Dongnae Bong-Seng Hospital, 2 Departmant of Internal Medicine, Dong-Eui Medical Center Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary tract infection and is usually associated with high mortality in Korea. We report a 78-year-old male survived from acute kidney injury due to septic shock caused by pyogenic liver abscess without aspiration. He was referred from gastroenterology of our hospital because of hypotension, anuria, thrombocytopenia, elevated liver enzyme and unknown origin fever. He had elevated serum BUN and creatinine levels, requiring hemodialysis treatment at the time of referral. But conventional hemodialysis was not available because of hypotension. So, we started continuous renal replacement therapy (CRRT) with inotropic agents at intensive care unit. We checked his abdominal CT scan before CRRT and multiloculated cystic/ necrotic lesion (5x5x3cm) in S7 was noted. The day after we started CRRT for him, we received his blood culture report. Klebsiella pneumoniae were identified in 3 sets of his blood samples. So we changed administrated antibiotics from ceftriaxone to meropenem and decide to prepare aspiration of abscess after observation. After 3 more days of continuous venovenous hemodiafiltration (CVVHDF), his blood pressure and urine output recovered to normal range and CRRT was stopped. We decided to deliver intravenous antibiotics for 6 weeks and maintain oral antimicrobial treatment for consolidate the effect of treatment without aspiration of abscess for technical difficulties. The patient has been treated follow-up care in outpatient department for 3 months. 124

126 37 Use of Cell-Cycle Arrest Biomarkers for Prediction of AKI in Infants Following Cardiac Surgery Katja M Gist 1, Jeffrey Alten 2, Danielle Soranno 3, Jane Duplantis 3, Julia Wrona 1, Christopher Altmann 4, Zhiqian Gao 5, Stuart L Goldstein 6, Sarah Faubel 4 1 University of Colorado, Children's Hospital Colorado, Aurora, 2 University of Alabama, Children s of Alabama, Department of Pediatrics, Division of Pediatric Cardiology, 3 University of Colorado, Department of Pediatrics, Renal Division, Children s Hospital Colorado, 4 University of Colorado, Department of Internal Medicine, Division of Nephrology and Hypertension, 5 Cincinnati Children s Hospital Medical Center, Heart Institute Research Core, 6 Cincinnati Children s Hospital Medical Center, Center for Acute Care Nephrology, Department Purpose: Acute kidney injury (AKI) following pediatric cardiac surgery (CS) is common, occurring in 20-40% of children, and is associated with increased morbidity and mortality. Early diagnosis of AKI has been hampered because rises in serum creatinine (SCr) the current method by which AKI is diagnosed occurs late after AKI. Currently, an increase in urine TIMP2*IGFBP1 0.3 ((ng/ml)2/1000) measured by the Nephrocheck (Astute Medical, La Jolla, CA) device is the only FDA approved AKI biomarker test, yet its approval is only for adults. The utility of TIMP2*IGFBP7 to predict AKI in infants is uncertain. The purpose of this study was to evaluate the utility of TIMP2*IGFBP7 for prediction of AKI in infants following CS. Methods: Stored urine samples from a large multi-center study were analyzed for TIMP2*IGFBP7 using the clinically validated Nephrocheck device according to manufacturers directions. Samples were measured at baseline (before CS) and then 2, 6, 12, 24, 48 and 72 hours after the initiation of cardiopulmonary bypass. The primary outcome was severe AKI defined by at least a 100% increase in SCr (KDIGO Stage 2 or greater) within 72 hours of cardiac surgery. Results: 94 infants (birth to 1 year) from 3 pediatric centers were included in the study, of which 26 (28%) developed severe AKI. Cross clamp time was 107 minutes (IQR: min) vs. those without AKI (62.5min, IQR: min)(p = 0.012) and urine output was 23.5ml/kg ml/kg vs ml/kg on the day of surgery (p=0.016) and vs ml/kg on post op day 1 (p = 0.016). Infants with severe AKI had a higher urinary TIMP2*IGFBP7 by 12 hours (1.1, IQR: vs. 0.4, IQR: )(p = )(Table 1). Urine TIMP2*IGFBP7 12 hours following CS demonstrated an AUC of 0.78, sensitivity of 0.81, specificity of 0.7 for a cutoff value of 0.78, which is more than double the cut-point used in adults. The relative risk of developing AKI when TIMP2*IGFBP7 was >0.78 was 4.48 times (95%CI: ) compared to those with TIMP2*IGFBP7 < 0.78 (p = ). Using the adult cut-off of 0.3 yielded a sensitivity of 0.9 and specificity of 0.5. This was not predictive of AKI. Conclusion: Similar to adults, urine TIMP2*IGFBP7 represents a sensitive, specific and predictive biomarker of AKI in children, although different urine cut-off levels than adults were necessary to identify AKI. Table on following page 125

127 Variable No AKI (n = 68) AKI (n = 26) p-value Age (days) / / Gender (male) 43 (63%) 20 (77%) 0.21 Cardiopulmonary bypass time (median, IQR) 150 (91.5, 186.5) (123, 205) 0.41 Cross clamp time (median, IQR) 63.5 (35.5, 97) 107 (62, 128) Urine output (ml/kg) Post-operative day / / Urine output (ml/kg) Post-operative day / / TIMP2*IGFBP7 (median, IQR) Baseline 0.5 (0.1, 1.6) 0.3 (0.2, 0.8) 0.99 TIMP2*IGFBP7 (median, IQR) 2 Hour 0.5 (0.2, 1.2) 1.1 (0.1, 2.3) 0.38 TIMP2*IGFBP7 (median, IQR) 6 Hour 0.7 (0.4, 1.5) 0.7 (0.5, 1.6) 0.99 TIMP2*IGFBP7 (median, IQR) 12 hour 0.4 (0.1, 1.1) 1.1 (0.9, 3.4) TIMP2*IGFBP7 (median, IQR) 24 Hour 0.3 (0.1, 1.2) 0.6 (0.1, 3.8) Plasma Pro-Enkephalin (penkid) and Renal Impairment in Severe Sepsis and Septic Shock: Data from the ALBIOS Trial Serge Masson 1, Pietro Caironi 2, Joachim Struck 3, Sandra Ferraris 4, Valentina Bellato 5, Oliver Hartmann 3, Andreas Bergmann 3, Luciano Gattinoni 2, Antonio Pesenti 2, Roberto Latini 1 1 IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan Italy, 2 Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, e Dipart, 3 sphingotec GmbH, Hennigsdorf, Germany, 4 U.O. di Anestesia e Rianimazione, Ospedale di Treviglio-Caravaggio, Treviglio, Italy, 5 U.O. Anestesia e Terapia Intensiva Generale, Istituto Clinico Humanitas, Rozzano, Italy Purpose of the study: Acute kidney injury (AKI) is a frequent complication in sepsis, associated with increased lethality. In such setting accurate prediction of incident AKI by biomarkers has been frequently impaired by delayed response and/or influence of the systemic inflammation. Pro-Enkephalin (penkid), a stable surrogate marker for Enkephalins, has emerged as a novel promising plasma biomarker reflecting kidney dysfunction in acute diseases. Here we describe performance of penkid as predictor of incident AKI in a large cohort of patients with severe sepsis or septic shock from the Albumin Italian Outcome in Sepsis (ALBIOS) trial (Caironi P et al., N Engl J Med Jul 3;371(1):84.). Methods: In a predefined biologic substudy of the ALBIOS trial, which randomized patients to albumin replacement in addition to crystalloids or crystalloids alone, EDTA plasma samples were obtained from 995 patients on days 1, 2 and 7 after randomization. Relations between plasma penkid concentrations, clinical characteristics and outcomes were analyzed. 126

128 Results: Multivariable regression analysis identified serum creatinine as the strongest independent determinant of elevated penkid levels (F=254.4, p<0.0001). When kidney function was normal (renal SOFA score=0), penkid levels were essentially within the normal range, whereas penkid increased with the renal SOFA score (Spearman correlation: r=0.66). Elevated penkid predicted incident acute worsening of renal function (AKI) as well as the use of renal replacement therapy (RRT) (unadjusted p< for both). In a multivariate Cox model after adjustment for serum creatinine, chronic kidney disease, and other variables penkid was an independent risk predictor for 90 day mortality (HR=1.6 [ ] per 1 IQR). Serial measurement of penkid further improved mortality risk prediction. Conclusions: In this large study including almost 1,000 patients with severe sepsis or septic shock from 40 Italian ICUs, plasma penkid was associated with both prevalent and incident kidney dysfunction and independently predicted mortality. The absence of influence of systemic inflammation on penkid levels along with the fact that penkid is assayed in plasma (not urine) makes it a novel kidney biomarker especially attractive for use in critically ill patients. 39 Milrinone Clearance in Critically Ill Infants with Acute Kidney Injury Following Cardiac Surgery Katja M Gist 1, Tomoyuki Mizuno 2, Julia Wrona 1, Jeffrey Alten 3, Zhiqian Gao 4, Stuart L Goldstein 5, David Nelson 6, David Cooper 6, Alexander A Vinks 2 1 University of Colorado, Children's Hospital Colorado, 2 Division of Clinical Pharmacology, Cincinnati Children s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati School of Medicine, 3 University of Alabama, Department of Pediatrics, Children s of Alabama, 4 Cincinnati Children s Hospital Medical Center, Heart Institute Research Core, 5 Division of Nephrology, Center for Acute Care Nephrology, Cincinnati Children s Hospital Medical Center and Department of Pediatrics, University of Cincinnati School of, 6 The Heart Institute, Division of Pediatric Cardiology, Cincinnati Children s Hospital Medical Center and 3Department of Pediatrics, University of Cincinnati School of M Purpose: Milrinone is used as an inotropic agent with vasodilating properties for treatment of ventricular dysfunction. Milrinone is eliminated as unchanged drug in the urine, and accumulates in acute kidney injury (AKI). The purpose of this study was to evaluate the effect of AKI on milrinone clearance in critically ill infants following cardiac surgery. Methods: Prospective multicenter observational study in infants undergoing surgery with cardiopulmonary bypass. Serum creatinine (SCr) was measured to assess milrinone pharmacokinetics (PK). Blood was collected at serial time points after milrinone initiation, dose changes and termination, and analyzed for using a validated LC-MS/MS assay. Pharmacokinetic parameters were estimated using MW/Pharm (Ver. 3.82, Mediware, The Netherlands). A 2-compartment population PK model was used in the Bayesian analysis. Milrinone clearance was allometrically scaled to account for body size differences. The primary outcome was severe AKI defined by at least a 100% increase in SCr (KDIGO Stage 2 or greater) within 72 hours of cardiac surgery. Results: 94 infants (67% male) were included. Twenty-six (28%) patients developed severe AKI. There was no difference in age, gender and weight between those with and without AKI. Milrinone clearance was significantly lower in pts with severe AKI (4.1L/h/70kg (IQR: 3-5.5) vs. (5.7L/h/70kg (IQR: 4-8))(p = 0.006). Clearance in those without AKI was also significantly lower than previously reported in PK studies in adult patients (18.9L/h/70kg). Urine output on the day of surgery and the first post-operative day was significantly 127

129 lower in those with AKI (p = and p = respectively). Lower milrinone clearance was associated with AKI (p = 0.02). Finally, AKI influences milrinone concentration and estimated highest steady state concentration. At a standard dose of 0.5mcg/kg/min, estimated steady state concentration was higher in AK pts (277ng/mL (range: ) vs. 203ng/mL (range: ))(p = )(Figure 1). Conclusion: Milrinone clearance is significantly lower in critically ill infants than in previously reported studies in adults. We suggest overdosing of milrinone in the setting of AKI is possible, and caution should be taken in critically ill infants. The estimated steady state concentration at a standard dose was lower than the target range. We suggest monitoring of milrinone concentrations with PK model based guidance could be beneficial in patients at risk for AKI. 40 Alkaline Phosphatase Protects Against Renal Inflammation Through Dephosphorylation of Lipopolysaccharide and Adenosine Triphosphate Esther Peters 1, Norbert Gretz 2, Peter Pickkers 1, Rosalinde Masereeuw 3 1 Radboud university medical center, Nijmegen, The Netherlands, 2 Medical Research Center, University of Heidelberg, Mannheim, Germany, 3 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht, The Netherlands. Background: Two phase-ii trials demonstrated improved renal function in critically ill patients with sepsisassociated Acute Kidney Injury (AKI) treated with the enzyme alkaline phosphatase (AP). Here, we elucidated the dual active effect on renal protection by human recombinant AP (recap) presumably related to dephosphorylation, thereby detoxifying, lipopolysaccharide (LPS). Methods: Human proximal tubular epithelial cells (ciptec) were incubated with LPS (10µg/ml) or TNF-α (10ng/ml). RecAP (10U/ml) was added 2h prior to LPS and cytokine production was studied after 24h by ELISA (n=5 per group). After 20 minutes, supernatant was collected to determine LPS-induced cellular adenosine triphosphate (ATP) release by bioluminescence (10µg/ml or 100 µg/ml LPS). Male SD rats were treated with placebo (n=6), LPS (n=6) or LPS+recAP (n=5). At t=0, LPS (IV, 0.3mg/kg) was administered to induce AKI, followed by an recap bolus (IV, 1000U/kg) at t=2h. GFR was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. Urine was collected during 16h. At 128

130 t=24h animals were sacrificed followed by blood and organ sampling. Results: In ciptec, recap significantly reduced LPS induced cytokine response of TNF-α (40.4±7.9%), IL-6 (47.5±3.1%) and IL-8 (39.6±2.4%). Similar effects were observed in ciptec stimulated with TNF-α (IL-6: 21.0±4.2%; IL-8: 21.6±4.6% reduction). Inactive AP had no effect on LPS- or TNF-α-induced cytokine response, confirming the relevance of dephosphorylation. Extracellular ATP concentrations increased following LPS incubation, which was more pronounced with a higher LPS concentration but reversed by recap preincubation. In vivo, LPS significantly prolonged FITC-sinistrin half-life (placebo: 19 [18-25] min, LPS: 55 [33-73] min), for which recap treated animals were protected (33 [29-47] min). Also, recap prevented LPSinduced increase in fractional urea and KIM-1 excretion and renal KIM-1 expression. Conclusion: These results indicate that the ability of recap to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect. 41 "Código IRA" Proposing a Rapid Response Team for the Detection and Management of Acute Kidney Injury in a University Hospital in Mexico Lilia Rizo-Topete 1, Giovanna Arteaga-Müller 1, Mara Olivo 1, Jesús Cruz 1, Elisa Guerrero 1, Concepción Sánchez 1, Jose G. Martínez 1, Dionicio Galarza 1, Edelmiro Pérez 1, Marco Hernández 1 1 Monterrey University Hospital Introduction: Acute Kidney Injury (AKI) is common in hospitalized and critically ill patients is, associated with high morbidity and mortality. The 5 to 7% develop it during internment, from 5 to 25% develop in ICU. Inpatients with severe AKI the Renal replacement therapy (RRT) serves as a cornerstone in the treatment, where mortality for AKI and multiple organ failure (MOF) is 50% and if RRT is required it would be 80%. Objective: If the fact of starting RRT increases morbidity and mortality, so why wait to start RRT if we can make a detection of a high risk patient during hospitalization. If we use the concept of Renal Angina we can identify minimal changes in serum creatinine, oliguria and volume overload in combination with the risk factors we could detect an early stage of AKI and prevent it. Methods: Based on the conceptual model of AKI and the proposal 0 by 25, in the 5 Rs between risk and recognizing a flowchart for detection inpatients at risk for AKI is proposed with an early management flowchart. To set the proposal in our hospital we made an statistical study with the following results: The Nephrology service has an average of 30 inpatients per day, the last 6 months were evaluated 438 patients, 193 were interconsulted by AKI, 118 were male (61.1%), Middle Age 52.1 years. The most common comorbidities were DM (39.9%) and hypertension (37.8%). Interconsultations were made for ICU and internal medicine (IM). The main cause of AKI was infectious. 90 (46.6%) patients need RRT and 30 of these stay in Chronic RRT (33.3%). Of all interconsulted patients died 31.6% but this increase in ICU to 59.6% Proposal: Our Hospital (third level) offers all medical services from ICU, Surgery, Neurosurgery, Orthopedics, Urology, Gynecology, Plastic Surgery and Internal Medicine (IM) this last with all its subspecialties like nephrology, because of this IM is the proposed base of the flowchart. Forming the team: IM service coordination and Nephrology. Primary care physician: Family, emergency room staff (surgeon, internist). Educate satellite services to identify: Emergency room (doctors and nurses), Surgical Service (General, Traumatology, Urology, Gynecology), Radiology, Oncology, Pulmonary and Critical Care Medicine. The proposal has been accepted by the Department of IM and will start the makeup of the group in January 2016, education block in February 2016 and the pilot group start activitiesin March Figure on following page 129

131 42 Ineffective Diuresis as a Biomarker During Early Postoperative Period Predicts Cardiac Surgery Associated Acute Kidney Injury Salvador Lopez-Giacoman 1, Carlos Garza-Garcia 2, Jose L Salas 2, Faeq Husain-Syed 1, Sara Samoni 1, Silvia De Rosa 1, Gerardo Gamba 2, Magdalena Madero 2, Claudio Ronco 1 1 Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy, 2 National Institute of Cardiology, México City, México Background: Cardiac surgery associated acute kidney injury (CSA-AKI) significantly increases morbidity and mortality. Difficulties in prediction and early identification of AKI have hindered the ability to develop preventive and therapeutic measures for this.. The present study aims at verifying that an ineffective diuresis, defined as less than 1.6ml/kg/h (IUO) during the early postoperative period (first 6h post-cardiopulmonary bypass (CPB)), may be a useful parameter to identify high risk patients (pts) for development of CSA-AKI. Methods: We performed a dual center prospective cohort study ( ) in pts requiring CPB, admitted to San Bortolo Hospital Vicenza/Italy and National Institute of Cardiology, México City/México. AKI was defined according to AKIN criteria. Pts were classified in two groups on the basis of urinary output (UO): 1) less than 1.6mL/kg/h (IUO group) and 2) equal or more than 1.6 ml/kg/h (control group). Primary outcome was AKI incidence, secondary outcomes were AKI severity, length of stay in intensive care unit, and 30-day mortality. Results: A number of 458 pts who underwent CPB were enrolled. The mean UO was 2.3±0.7 ml/kg/h. During the first 96h post-cpb, 158 pts (34.5%) developed AKI, among these 61 pts (13.3%) had severe AKI. In the IUO group, 98 pts developed AKI (45.4%), while in the control group, AKI occurred in 60 pts (24.8%) (p<0.001). Moreover, 44 pts (20.4%) and 17 pts (7%) respectively in the IUO group and control group had severe AKI (p<0.001). Ineffective diuresis was associated with increased odds of AKI and severe AKI [adjusted odds ratio OR 4.2 ( , CI 95% p:0.001) and 3.8 ( , CI 95% p:0.001) respectively]. The value of 130

132 1.6mL/kg/h for UO may be considered as cut-off value to predict CSA-AKI with an AUC of Table 1 summarizes characteristics of two groups. Conclusion: An ineffective diuresis (<1.6mL/kg/h) during the early postoperative period should be included in the early evaluation of cardiac surgery pts to identify those at clinical high risk of CSA-AKI, could even improve the performance of new molecular biomarkers NGAL, TIMP2/IGFBP7, KIM-1 and others. 131

133 43 Endothelial Progenitor Cell-Derived Extracellular Vesicles Protect From Sepsis-Associated Acute Kidney Injury Vincenzo Cantaluppi 1, Davide Medica 2, Alessandro D Quercia 2, Sergio Dellepiane 2, Marita Marengo 3, Giovanni Camussi 2 1 University of Eastern Piedmont, 2 University of Torino, 3 ASLCN1 Cuneo Sepsis-associated AKI is due to a detrimental effect of pro-apoptotic circulating plasma factors able to induce endothelial (EC) and tubular epithelial (TEC) cell injury. Endothelial Progenitor Cells (EPC) are bone marrowderived precursors able to accelerate tissue regeneration through the release of paracrine mediators such as extracellular vesicles (EV), small particles carrying RNA.The aim of this study was to evaluate the protective role of EPC-derived EV on EC and TEC injury induced by plasma of septic patientts. We enrolled in the study 20 critically ill patients with septic shock and AKI Peripheral blood EPC were evaluated by FACS (CD34+/CD133+/flk-1+ cells) and isolated on fibronectin-coated plates. EV were isolated from EPC supernatants and characterized for RNA content. In vitro, kidney-derived EC and TEC were cultured with septic plasma and EPC EV from healthy subjects. Patients with sepsis-associated AKI presented an increased number of circulating EPC. However, isolated EPC showed a decrease of proliferation and of EV release. EV isolated from EPC of healthy donors were internalized in both EC and TEC and protected from septic plasma-induced injury. On EC, septic plasma induced leukocyte adhesion, decreased angiogenesis through enos reduction and induced apoptosis through activation of the complement cascade. EPC EV reduced all these effects through the transfer of pro-angiogenic microrna (mir-126, mir-296) and mrna coding for inhibitors of apoptosis (Bcl-XL) and of complement activation such as CD55 (DAF), CD59 and Factor H. On TEC, septic plasma induced death receptor (Fas, TNF- R) apoptosis and mitochondrial dysfunction through decrease of PGC-1alpha. In addition, septic plasma induced loss of cell polarity as assessed by TEER and a decreased expression of the tight junction protein ZO-1, the endocytic receptor megalin and other TEC-specific solute carriers. All these effects on TEC were reduced by EPC EV stimulation. The EV-associated protection on both EC and TEC was significantly abrogated by their pre-treatment with RNase, the enzyme able to destroy mrna and microrna within EV. In conclusion, EPC isolated from peripheral blood of patients with sepsis-associated AKI showed functional alterations, a decreased proliferation rate and EV release. EPC-derived EV may be exploited as innovative therapeutic approach in sepsis-associated AKI for their ability to inhibit apoptosis and functional alterations of EC and TEC. 132

134 44 Immunomodulation of Regional Citrate Anticoagulation in Acute Kidney Injury Requiring Renal Replacement Therapy: A Randomized Controlled Trial Sadudee Peerapornratana 1, Sasipha Tachaboon 1, Khajohn Tiranatanakul 1, Nattachai Srisawat 1 1 Chulalongkorn University, Bangkok, Thailand Background: Currently, Regional Citrate Anticoagulation (RCA) has become the standard anticoagulation for acute kidney injury (AKI) patients requiring continuous renal replacement therapy (CRRT) support. Beyond the anticoagulant effect, data from in vitro showed RCA might have anti-inflammatory effect. We aim to study the immunomodulation effect of RCA in patients with AKI undergoing CRRT. Methods: This prospective randomized controlled trial was conducted at medical and surgical Intensive Care Unit, King Chulalongkorn Memorial hospital. The participants were randomized to either regional citrate group (n = 15) or control group (n = 15). Blood samples were collected at baseline, six hours and 24 hours after starting CRRT. We measured CD11b, human leukocyte antigen-dr (HLA-DR) expression by using flow cytometry technique. We also tested the RCA effect on coagulation cascade by measurement the level of C3a, C5a and plasminogen activator inhibitor-1 (PAI-1) in plasma by using enzyme-linked immunosorbent assay technique. Results: Thirty AKI patients with CRRT were recruited and randomized into control and citrate group. The demographic data between two groups are not different in each group. The percentage change of CD11b (0-24 hours) in RCA group had significantly higher than the control group, vs. 7.1 %, p = 0.02), concordantly with the percentage change of HLA-DR, vs %, p = 0.02). The percentage change of PAI-1 in RCA had also decreasing higher than the control group ( vs , p = 0.03). However, there was no significant different level of C3a and C5a between two group over 24 hours during CRRT. The mortality rate at day-28 after enrollment between RCA and control group was no significant difference. Conclusion: RCA had the benefit beyond the anticoagulation effect by decreasing the inflammatory process during CRRT. The larger randomized controlled trial is still warrant. 45 Low Normal Values of Circulating Immune Cells with Increased Proportion of Vδ2 T-Cells are Associated with Acute Kidney Injury after Endovascular Thoraco-Abdominal Aortic Repair Ivan Gocze 1, Katharina Ehehalt 1, Bernhard M Graf 1, Ed K Geissler 1, Thomas Bein 1, Piotr Kasprzak 1, Hans J Schlitt 1, John A Kellum 2, James A Hutchinson 1, Philipp Renner 1 1 University Medical Center Regensburg, 2 Department of Critical Care Medicine, University of Pittsburgh Purpose To assess the postoperative course of tubular cell cycle arrest biomarkers expression after mild ischemicreperfusion injury and intravenous contrast during endovascular multi-branched aortic repair and to identify cellular immunological phenotype associated with tubular cellular stress and acute kidney injury (AKI). Methods Prospective single-center pilot study including 18 patients. Incidence of tubular cellular stress as measured by expression of cell cycle arrest biomarkers, incidence of AKI, clinical and laboratory parameters were evaluated. Robust immunological profile of 62 immune cell subsets based on flow cytometry was assessed before and

135 hours after surgery. Results Duration of surgery (p=0.03) and postoperative level of [TIMP-2] [IGFBP7] (p=0.05) were associated with AKI. Strong cellular immune response with decrease of absolute numbers of circulating T, B and natural killer (NK) cells within first 24 hours was detected in all patients (from 1.29 /nl (SD 0.60) to 0.81 /nl (SD 0.37), p<0.01). By contrast, only limited cellular reaction was detected in patients, who developed AKI (from 0.96 /nl (SD 0.49) to 0.73 /nl (SD 0.38), p=0.36). This was due to significantly lower cell number prior to surgery as compared to patients without AKI (1.61 /nl vs 0.96 /nl, p=0.02). Trend to increased proportion of Vδ2 T-cells was identified in patients at AKI- risk, while other T-cells decreased, showing moderate correlation between cell cycle arrest biomarkers and number of Vδ2 T-cells (r=0.46, p=0.07) [Fig 1]. Conclusion Strong systemic immune response with migration of cells from peripheral blood compartment in to organs occurs after surgery. Low pre-operative level of circulating T, B and NK cells and increased proportion of Vδ2 T-cells within first 24 hours represents the immunological risk factors for early AKI after aortic surgery. Fig 1. Comparison of T-cells subgroups showing increased absolute count of Vδ2 T-cells in patients with cellular stress and patients with AKI, while CD4 and CD 8 cells are decreased. * p<0.05, ** p<

136 46 Biomarkers of Acute Kidney Injury and Outcome in Critically Ill Patients Matthieu Legrand 1, Joachim Struck 2, Alain Cariou 1, Nicolas Deye 1, Bertrand Guidet 1, Samir Jaber 1, Marc Leone 1, Antoine Vieillard Baron 1, Etienne Gayat 1, Alexandre Mebazaa 1 1 Department of Anesthesiology and Intensive Care, Saint Louis - Lariboisière - Fernand Widal University Hospital, AP-HP, Paris, France, 2 sphingotec GmbH, Hennigsdorf, Germany Purpose of the study: Acute kidney injury (AKI) has been associated with an increased risk of poor outcome in critically ill patients. Pro-Enkephalin (penkid), a stable surrogate marker for enkephalins, has emerged as a promising novel plasma biomarker predicting renal function and mortality. The objective of this study was to explore the diagnostic and prognostic value of a panel of biomarkers of renal injury and renal function in critically ill patients. Methods: The French and european Outcome registry in Intensive Care Units (FROG-ICU) study was a multicenter observational study, including 2087 critically ill consecutive patients. Plasma and urine samples were collected on admission. Primary endpoint was AKI, defined by KDIGO definition using the creatinine criteria on admission as the baseline. Secondary endpoints included severe AKI (defined by KDIGO stage 2 or 3), transient AKI and major adverse kidney events (MAKE, including death, RRT and non-renal recovery). The association between outcomes and biomarkers was assessed by univariate analysis. Predictive values were assessed using area under the ROC curves. Results: 893 (43%) patients developed AKI including 716 patients with severe AKI. 338 (37%) patients had transient AKI. 832 (40%) patients developed a MAKE including 480 requiring RRT. On admission all biomarker levels were higher in patients with AKI compared to non-aki: (63.3 to 193.3) vs 43.2 (30.6 to 66.8) pmol/l for penkid, 1.8 (1.2 to 2.7) vs 0.8 (0.6 to 1) mg/dl for Screat, 494 (247.8 to 909.2) vs 126 (74 to 225.8) for pngal, (158.9 to 1500) vs 62.5 (27 to 204.9) for ungal, 2 (1.4 to 3) vs 1 (0.8 to 1.4) for pcyst and 0.8 (0.2 to 3.4) vs 0.2 (0.1 to 1) for ucyst (all p<0.001). Area under the ROC curve (AUC-ROC) for AKI was: [ ] for penkid, [ ] for pngal, [ ] for pcyst. AUC-ROC for transient AKI was: 0.63 [ ] for Screat, [ ] for penkid, [ ] for pngal and [ ] for pcyst. AUC-ROC for MAKE was: [ ] for Screat, [ ] for PenKid, [ ] for pngal and [ ] for pcyst. A strong correlation was observed between penkid and egfr on admission (Spearman r=-0.68, p<0.001) Conclusion: Plasma penkid, pngal and Cystatin C appear to be valuable biomarkers of AKI in critically ill patients. penkid is not influenced by systemic inflammation. 135

137 47 Urinary TIMP2xIGFBP7 Detects Patients with Positive Urine Microscopy Findings Moritz B Schanz 1, Mark D Alscher 1, Martin Kimmel 1 1 Robert-Bosch Hospital, Stuttgart, Germany Background and objectives Urine microscopy is an established technique to assess kidney disease, including acute kidney injury (AKI), and can add valuable information about the mechanism of damage. However, it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in practice. A rapid biomarker test that identifies patients to have positive urine microscopy findings would likely enable more efficient use of this technique. We hypothesized that urinary TIMP2xIGFBP7, a new FDA-approved test to assess AKI risk, would indicate likelihood of a positive urine microscopy finding in emergency department (ED) patients. Design, settings, participants & measurements 400 patients were enrolled in the ED; thereof 362 patients had available both TIMP2xIGFBP7 and Urine-Score (U-Score) data at enrollment. TIMP2xIGFBP7 results are reported in units of (ng/ml)2/1000. U-Score was assessed through urine microscopy as described previously. AKI was assessed within 24 hours of enrollment using serum creatinine and urine output. Results Fifteen (4%) of 362 patients had a U-Score >0. When patients were stratified into three groups using the validated TIMP2xIGFBP7 cutoffs of 0.3 and 2.0, the proportion of patients with a positive U-Score increased across the three strata from 1% to 6% to 24% (p<0.001). At the 0.3 cutoff, TIMP2xIGFBP7 had a sensitivity of 87%, specificity of 62%, negative predictive value (NPV) of 99% and positive predictive value (PPV) of 9% for prediction of a positive U-Score. At the 2.0 cutoff, specificity increased to 95% and PPV increased to 24%. Conclusions In ED patients, urinary TIMP2xIGFBP7 had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary TIMP2xIGFBP7 may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources. 136

138 48 Vitamin D Deficiency is Common in Severe Acute Kidney Injury Danni Bear 1, Linda Tovey 1, Katie Lei 1, Helen Dickie 1, Kathryn Chan 1, John Smith 1, Marlies Ostermann 1 1 Guy's & St Thomas Hospital London (UK) INTRODUCTION In patients with chronic kidney disease (CKD), Vitamin D deficiency is very common and the supplementation with active Vitamin D preparations is recommended. To date, it is unknown whether patients with severe acute kidney injury (AKI) also suffer from Vitamin D deficiency and whether there is a role for supplementation. OBJECTIVES To determine Vitamin D3 levels in patients with AKI stage 3 on the day of diagnosis of AKI stage 3 and 6 days later. METHODS We prospectively identified adult patients on the Intensive Care Unit (ICU) with AKI III. Following informed consent, we measured plasma Vitamin D3 levels at diagnosis of AKI III and 6 days later. Vitamin D3 levels were measured by immunoassay. Vitamin D3 deficiency was defined as Vitamin D3 <30nmol/L. We differentiated between patients with and without continuous renal replacement therapy (CRRT) and excluded patients on parenteral nutrition. RESULTS We analysed 54 patients of whom 12 patients received CRRT for 6 days, 31 patients had CRRT for 1-5 days and 12 patients did not have CRRT. Vitamin D3 deficiency was very common in all groups (Table 1). There was no clear evidence that CRRT was contributing. CONCLUSIONS Vitamin D3 deficiency is common in patients with AKI III. More research is necessary to investigate its impact on patient outcome and the role of Vitamin D supplementation. Mean Vitamin D3 on day of diagnosis of AKI III [nmol/l] Presence of Vitamin D3 deficiency on day of AKI III CRRT for 6 days CRRT for 1-5 days % 74% 84.6% Mean Vitamin D3 on day 6 of AKI III [nmol/l] AKI III without CRRT 137

139 49 Serum Cystatin C Predicts Renal Recovery Earlier Than Serum Creatinine Among Hospitalized Patients With Acute Kidney Injury Kamel Gharaibeh 1, Abdurrahman Hamadah 1, Ziad El-Zoghby 1, John Lieske 1, Nelson Leung 1 1 Mayo Clinic, Rochester, MN Background/Aim Limited evidence suggests serum cystatin C (cys C) peaks earlier than serum creatinine (scr) during the course of acute kidney injury (AKI). Earlier identification of AKI recovery could allow better resource utilization and earlier hospital discharge. Thus, we conducted an observational pilot study to determine the relative time course of scr and cys C in hospitalized patients with AKI in our tertiary medical center. Methods Hospitalized patients with AKI at our institution between May and November of 2015 who had serial scr and cys C levels measured during their hospitalizations were identified. AKI was defined based on the Acute Kidney Injury Network criteria. Demographic data, baseline creatinine, causes of AKI, and other significant comorbidities were collected by review of the medical record. Results Overall, 29 patients were identified. Mean age was 57.1 ± 14.3 years, 48.3 % were women, 93% were white, and median BMI was 29 kg/m2. Baseline median creatinine was 0.9 (IQR ), 17% had a kidney transplant and 42% had received steroids. Co-morbidities included hypertension (55%), malignancy (52%), diabetes (31%), thyroid disorder (24%) and heart failure (10%). Two (7 %) patients had AKI stage I, 6 (21 %) AKI stage II, and 21 (72 %) AKI stage III, with 10 (34%) requiring dialysis. The cause of AKI was ATN in the majority of patients (69%). Overall, cys C peaked before scr in 69 % of patients (10% 3 days, 24% 2 days, 34% 1 day prior), and on the same day in 28% of them. In only 1 patient (3%) cys C peaked after SCr (2 days). The cause of AKI in this patient was obstruction. Exploratory analyses did not suggest any effect of the various comorbidities on the timing of peak cys C as compared to scr. Overall cys C peaked a mean of 1.1 days prior to scr (95% CI ; p<0.001) and performed equal or better than scr in 97% of patients in this study for monitoring recovery from AKI Conclusion This pilot study suggests cys C peaks earlier than scr in the majority of hospitalized AKI patients. A larger study is warranted to confirm the magnitude of this effect, and the potential confounders (if any). These findings have significant clinical implications for managing AKI with the potential for shortening hospital stay and reducing cost. Timing of Cys C peak compared to creatinine peak N (%) -3 days 3 (10%) -2 days 7 (24%) -1 day 10 (34%) Same day 8 (28%) +2 days 1 (3%) Total 29 (100%) 138

140 50 AMPK is activated in mice after CLP and that it protects from AKI Yujie Ma 1, Kui Jin 2, Hui Li 1, Jacob Volpe 1, David Emlet 1, Xiaoyan Wen 1, Michael R Pinsky 1, Brian S Zuckerbraun 1, John A Kellum 1, Hernando Gomez 1 1 University of Pittsburgh, 2 Center of Critical Care, An Hui Provincial Hospital, Hefei, Anhui, China Purpose: The role of energy regulatory pathways in the protection from sepsis-induced acute kidney injury (AKI) is uncertain. We have previously shown that AMP-activated protein kinase (AMPK), a master regulator of energy balance, is activated early after cecal ligation and puncture (CLP), and its exogenous activation with AICAR limits sepsis-induced AKI and inflammation. Here we tested the hypotheses that activation of AMPK with AICAR H1: limits both ATP depletion and inflammation, and H2: improves clinical status and survival. Methods: H1: 15 C57BL/6 wild type, week old, 30-35g mice were subjected to CLP (n=12) or sham surgery (n=3), and sacrificed after 8 h to measure renal tissue ATP. H2: 27 mice were subjected to CLP (n=18) or sham surgery (n=9) were randomly assigned to pretreatment with AICAR (100 mg/kg intraperitoneal (IP), 24h before), Compound C (AMPK inhibitor, 30mg/kg IP) or vehicle (control). Functional status was assessed using a 6-item clinical severity score (score range 0-3) daily for 7 days. Results: AMPK activation limited the decline in renal ATP (Fig 1A), and was associated with a trend towards improved mortality (Fig 1B), whereas compound C was associated with worse clinical score (Fig 1C) and survival (Fig 1B). Conclusion: AMPK activation limits ATP depletion in the kidney, decreases inflammation, and was associated with decreased clinical severity score and with a trend towards improved survival. These data suggest that immune modulation and energy conservation may play a role in the protective effects of AMPK activation during sepsis. 139

141 51 Clinical and Subclinical Acute Kidney Injury in An Experimental Model of Sepsis Xiukai Chen 1, Xiaoyan Wen 1, Jicheng Zhang 1, David R Emlet 1, John A Kellum 1 1 The Center of Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, School of Medicine Propose: Sepsis is commonly followed by clinically apparent acute kidney injury (AKI) but injury to the kidney may occur even when serum creatinine is normal. This subclinical AKI may increase risk for recurrence of AKI, chronic kidney injury (CKD) and even death. This study was intended to document patterns of subclinical AKI and to explore the mechanisms underlying sepsis associated AKI. Methods: Male BALB/c mice were divided into various sepsis severities (mild, moderate and severe) using a cecal ligation and puncture (CLP) model according to different punctures (1, 2, and 3) or sham surgery. In different animals, blood and kidneys were harvested at 6hrs, 24hs and 14ds. Results: Mild CLP did not result in any differences, while severe CLP resulted in high mortality (75%). Increased tissue staining for neutrophil gelatinase-associated lipocalin (NGAL) and diffuse kidney inflammation was seen at 6hrs in moderate and severe groups while expression of kidney injury molecular- 1(KIM-1) in kidney tissue and serum creatinine increased only in the severe group. NADP/NADPH ratio increased at 24hrs in the severe group. Interleukin-6(IL-6) in blood was elevated at 6h and 24hrs while TNFalpha elevated at 24hrs in all groups. The expression of bone morphogenetic protein receptor type 1a (BMPR1a) increased in started from 6h to 24 hours and continued to 14 days without concomitant changing of Bone Morphogenetic Protein 7(BMP7) in moderate and severe groups. Although serum creatinine concentration in CLP groups was similar to sham group, NGAL in kidney tissue was high with evidence of fibrosis including increased level of collagen I at 14 days post injury. Conclusions: Moderate CLP induced sepsis was a reliable model to study subclinical AKI. In addition to oxidase stress and inflammatory reactions, epithelial cell injury, fibrosis was also seen even as early as 14 days post injury. The imbalance of BMP7/BMPR1a signaling emerged to be a potential therapeutic target for preventing CKD in sepsis. 52 Urinary TIMP2xIGFBP7 for Risk Prediction of Cardiorenal Syndrome Kimmel Martin 1, Moritz B Schanz 1, Mark D Alscher 1 1 Robert-Bosch Hospital, Stuttgart, Germany Background and objectives Acute decompensated heart failure (ADHF) is a common reason for hospitalization and the risk of acute kidney injury (AKI) is high. The interaction of cardiac and renal dysfunction is well known as cardiorenal syndrome, and early detection of patients at risk for this condition is important. We tested urinary TIMP2xIGFBP7, a new FDA-cleared test to assess AKI risk, in a cohort of ADHF patients in the emergency department (ED). Design, settings, participants & measurements 400 patients were enrolled in the ED. Serum creatinine values and urine output were recorded for AKI staging by KDIGO criteria. Urinary TIMP2xIGFBP7 was analyzed in samples collected during the first day (at 0, 6 and 140

142 24h) after enrollment. We examined the predictive ability of TIMP2xIGFBP7 for development of KDIGO stage 2 or 3 within 12 hours of sample collection in the 40 patients with ADHF, urinary TIMP2xIGFBP7, serum creatinine, and urine output data. Operating characteristics were determined for the previously validated TIMP2xIGFBP7 cutoffs of 0.3 and 2.0. TIMP2xIGFBP7 results are reported in units of (ng/ml)2/1000. Results Seven (17.5%) of the 40 ADHF patients met the AKI stage 2-3 endpoint. TIMP2xIGFBP7 discriminated for risk of AKI stage 2-3 with an AUC (95% confidence interval) of 0.84 ( ). At the 0.3 cutoff for TIMP2xIGFBP7, the sensitivity was 86% and the specificity was 71% for prediction of AKI stage 2-3. At the 2.0 cutoff, the sensitivity was 43% and the specificity was 95%. Conclusions In ADHF patients presenting to the ED, urinary TIMP2xIGFBP7 enables good risk prediction of cardiorenal syndrome. 53 Intraoperative CRRT Could be Useful During Liver Transplantation in Critically Ill patients with Renal Dysfunction Seung Don Baek 1, Mun Jang 1, Wonhak Kim 1, Shin Hwang 1, Sung-Gyu Lee 1, Eun Kyoung Lee 2, So Mi Kim 3, Jai Won Chang 1 1 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, 2 Dankook University College of Medicine, Cheonan-si, Chungnam, South Korea, 3 Jeju National University School of Medicine, Jejusi, Jeju, South Korea Purpose Renal dysfunction frequently complicates liver transplantation (LT). Volume overload aggravate the morbidity and mortality in major surgical procedure. Continuous renal replacement therapy (CRRT) is well known for its hemodynamic stability and tolerance. However, comparative outcomes of CRRT during LT are unproven. Methods We investigated retrospectively clinical outcomes of intraoperative CRRT compared with those of non-dialytic conservative treatment in 240 LT patients with preoperative renal dysfunction (estimated GFR (egfr) < 60 ml/min/1.73m2) from 1st January 2011 to 31st December Results Compared with non-dialytic conservative group (n=98, age 53.1+/-8.0 yrs, M:F=64:34), intraoperative CRRT group (n=142, age 51.3+/-10.2 yrs, M:F=108:34) revealed more severe critical illness including MELD score (34.9+/-8.8 vs /-10.2, p<0.005), ascites (83.1% vs. 64.3%, p=0.001), hepatic encephalopathy (73.2% vs. 38.8%, p<0.005), preoperative renal dysfunction (egfr 31.4+/-15.4 vs /-11.4, p<0.005), ventilatory care (52.1% vs. 10.2%, p<0.005), and ICU admission (52.1% vs. 10.2%, p<0.005). Despite of above problems, there was no significant difference between two groups in 1-year survival, graft failure, recovery of renal dysfunction, frequency of hyperkalemia and postoperative complications by multivariate analysis. In an adjusted variables model, intraoperative CRRT group significantly escaped volume overload such as pulmonary edema (OR 0.396, 95% CI , p=0.002) and the unnecessary change of serum sodium concentration > 10 mmol/l (OR 0.208, 95% CI , p=0.008). 141

143 Conclusion Considering more severe critical illness of intraoperative CRRT group and low frequency of volume overload, intraoperative CRRT could be useful during LT in critically ill patients with renal dysfunction. In the future, randomized controlled studies to prove the definite advantage of intraoperative CRRT during LT are needed. 54 Early CRRT Could be Defined as the Initiation of CRRT within 24 hours after vasopressor infusion Seung Don Baek 1, Hyang-Sook Park 1, Mi-Soon Kim 1, Eun Kyoung Lee 2, So Mi Kim 3, Jai Won Chang 1 1 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, 2 Dankook University College of Medicine, Cheonan-si, Chungnam, South Korea, 3 Jeju National University School of Medicine, Jejusi, Jeju, South Korea Purpose Although institution of early continuous renal replacement therapy (ecrrt) reduces morbidity and improves the conditions of the patients with septic acute kidney injury (AKI) by removing inflammatory cytokines, the optimal timing for the initiation of ecrrt is uncertain and requires practically feasible definition and acceptable evidences. Methods We investigated the clinical impacts of three parameters about time interval such as (1) from the start of vasopressor to the initiation of CRRT (Tvaso-CRRT), (2) from the time of ICU admission to CRRT (TICU- CRRT), and (3) the time from endotracheal intubation to CRRT (Tendo-CRRT), on morbidity and mortality of 75 patients (age / yrs, M:F=39:36, SOFA score 14.4+/-2.2, NGAL 1002+/-390 ng/ml, procalcitonin 76+/-129 ng/ml, RIFLE criteria R:17, I:26, F:32) who need CRRT for septic AKI. 142

144 Results The proportion of the patients with Tvaso-CRRT (median 21, range hours) less than 24 hours was significantly higher in survival group than non-survival group (26/30(86.7%) vs. 19/45(42.2%), p<0.005). Tvaso-CRRT less than 24 hours and SOFA score were independent factors associated with 28-day mortality (HR 0.430, 95% CI , p=0.022; HR 1.434, 95% CI , p=0.001) and 90-day mortality (HR 0.460, 95% CI , p=0.018; HR 1.340, 95% CI , p=0.006). TICU-CRRT (19, 6-52 hours) and Tendo-CRRT (13, 3-39 hours) were significantly correlated with the length of stay in ICU (p=0.005) and the duration of mechanical ventilation (p=0.005). Conclusion Considering the possible therapeutic measurement by physician on the basis of the results in this study, the definition of early CRRT could be Tvaso-CRRT less than 24 hours. TICU-CRRT and Tendo-CRRT were only associated with morbidity, but not mortality. In the future, randomized controlled trials are needed to prove the usefulness of our definition of early CRRT. 143

145 55 Clinical Factors to Discriminate the AKI Patients Requiring CRRT over 6 days Seung Don Baek 1, Hyang-Sook Park 1, Mi-Soon Kim 1, Eun Kyoung Lee 2, So Mi Kim 3, Jai Won Chang 1 1 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, 2 Dankook University College of Medicine, Cheonan-si, Chungnam, South Korea, 3 Jeju National University School of Medicine, Jejusi, Jeju, South Korea Purpose To avoid unnecessary early CRRT increasing cost without measurable clinical benefit, the factors to predict the duration of CRRT should be settled. We investigated factors influencing the duration of CRRT including clinical parameters and the biomarker of AKI such as NGAL and serum creatinine. Methods We extracted 124 patients who required CRRT for AKI in ICUs and were followed for 28 days from January 1st to December 31st, We excluded patients with chronic kidney disease, prior liver or kidney transplantation, and death during 28-day follow-up. We divided patients (n=124, median duration of CRRT: 6 days) into the shorter group (=< 6 days, n=65) and longer group (>6 days, n=59) and retrospectively analyzed. We also tested the performance of the predictors. Results The presence of acute respiratory distress syndrome (p=0.002), mean arterial pressure (p=0.086), urine output (ml/kg/hour, p=0.006), the duration of mechanical ventilation (p<0.005), the duration of ECMO (p=0.001), platelet count (p=0.013), serum creatinine (p=0.086) and serum total CO2 (p=0.064) were considered significantly correlated with the duration of CRRT in univariate linear regression analysis. Among them, urine output (p=0.012) and duration of ventilation (p<0.005) were independently significant in multivariate analysis. As the predicting factors of the duration of CRRT over 6 days, urine output (OR 0.381, 95% CI , P=0.002), application of mechanical ventilation (2.321, , p=0.03), and the presence of ECMO support (5.187, , p=0.003) were independent factors in multivariate logistic regression analysis. Serum creatinine and NGAL were not significant. A clinical model using above three parameters demonstrated the discriminatory ability with AUC of (95% CI, ) to predict the duration of CRRT over 6 days. Conclusion Simultaneously considering of urine output, mechanical ventilation and ECMO could select the AKI patients requiring CRRT over 6 days and avoid unnecessary early CRRT. These criteria should be confirmed by other randomized studies. Figure on following page 144

146 56 IGFBP7 and TIMP2 Expression and Secretion in Human Kidney Tubule Epithelial Cells David R Emlet 1, Nuria Pastor-Soler 2, Allison Marciszyn 1, Xiaoyan Wen 1, Hernando Gomez 1, Jacob K Volpe 1, William H Humphries IV 3, Xiukai Chen 1, Seth Morrisroe 1, John A Kellum 1 1 University of Pittsburgh, 2 University of Southern California, 3 B&B Microscopes Purpose: Acute kidney injury (AKI) continues to be a significant issue in the critically ill patient, and discovery of novel biomarkers for the disease have not yet significantly contributed to improvements in patient care. Our group has recently identified IGFBP7 and TIMP2 as early superior biomarkers for prediction of development of AKI in critically ill patients, but their potential role in the disease remains unknown. Methods: Human kidney samples were procured from the local Organ Procurement Organization CORE with institutional approval. Cortex tissue was isolated and dissociated with Collagenase and sieving. Viable cells were cultured to confluence, and epithelial cells of proximal (PTEC) and distal (DTEC) tubule origin were immunoaffinity isolated with antibodies directed against CD13 and CD227 respectively using the Dyanbead pan-mouse IgG system. Cells and conditioned media were characterized and studied by immunoblot and immunofluorescence. Immunofluorescence of fixed cortical tissue sections was used to assess protein expression in vivo. Summary: In immunoaffinity isolated cells in culture, both proteins are expressed and secreted, where IGFBP7 is primarily secreted by cells of proximal origin, and TIMP2 is primarily secreted by cells of distal origin. Furthermore, TIMP2 is primarily secreted from the apical/luminal surface of polarized cells. In human cortical kidney tissue, 145

147 IGFBP7 and TIMP2 were compared to panels of markers for proximal and distal tubule cells, where IGFBP7 staining is seen strongly in the luminal brush border region of a subset of proximal tubule cells, and TIMP2 is mostly seen intracellularly in distal tubule cells. Lastly, while tubular co-localization of both markers can be identified with the markers of injury Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), only partial co-localization can be identified, suggesting a separate mechanistic and temporal profile of these markers from injury markers. Conclusion: Together, these data show that IGFBP7 and TIMP2 are expressed and secreted in primary human kidney tubule cells, exhibit differential expression and secretion patterns within cells and across tubule types, and suggest that the expression and secretion of IGFBP7 and TIMP2 only partially correlates with markers of injury. This work sets into place the ability to investigate any potential role of these markers in the etiology of AKI. 57 Mitochondrial Pathology And Glycolytic Shift During Proximal Tubule Atrophy After Ischemic AKI Hui Geng 1, Rongpei Lan 1, Prajjal Singha 1, Pothana Saikumar 1, Erwin Bottinger 2, Joel Weinberg 3, Manjeri Venkatachalam 1 1 University of Texas Health Science Center, San Antonio, TX, USA, 2 Mount Sinai School of Medicine, New York, NY, USA, 3 University of Michigan Medical Center, Ann Arbor, MI, USA A subset of proximal tubule cells regenerating after ischemia-reperfusion injury (IRI) fail to redifferentiate after early dedifferentiation, undergo premature growth arrest, and become atrophic. These atrophic cells display pathological signaling that triggers production of profibrotic peptides and proliferation of fibroblasts. We now report that tubule atrophy after IRI is associated with striking alterations of metabolism, glycolytic enzyme expression and mitochondrial structure. Proximal tubule regeneration after IRI was accompanied by enhanced hexokinase activity, accumulation of pyruvate and lactate, and increased expression of glycolytic enzymes. Late during regeneration, protein expression of hexokinase 2 (HK2), phosphofructokinase platelet (PFKP), 6- phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), and pyruvate kinase M2 (PKM2) increased markedly in atrophic tubules, unlike declines seen during normal recovery. Tubules undergoing atrophy showed simplified mitochondria, reduced mitochondrial number, and autophagolysosomes containing damaged mitochondria. Atrophic tubules exhibited depletion of Mpv17L, an inner membrane protein that protects mitochondria from oxidant damage. Also, atrophic tubules showed increased S293 phosphorylation of pyruvate dehydrogenase E1 alpha, consistent with inhibition of this rate limiting enzyme for pyruvate entry into Krebs cycle. These alterations were accompanied by expression of hypoxia markers and prevented by TGF-beta antagonism. Hypoxia can trigger TGF-beta and both hypoxia and TGF-beta may induce glycolysis and mitochondrial oxidant species. Therefore, we examined metabolic regulation by hypoxia and HIF1 alpha in cultured proximal tubule cells. Exposure to 0.5% O2 for 48 hours increased the expression of PFKP, PFKFB3, and PKM2 proteins. HIF1 alpha knockdown abrogated these hypoxic effects. Hypoxia also induced S293 phosphorylation of pyruvate dehydrogenase E1 alpha in a HIF1 alpha independent manner. Taken together, our findings suggest that tubulointerstitial hypoxia gives rise to a metabolic switch from oxidative metabolism to glycolytic metabolism in proximal tubules regenerating after IRI. Failure to reverse the metabolic switch appears to be an integral part of the process that prevents tubule redifferentiation and causes tubule atrophy after IRI. How these metabolic alterations relate to other aspects of the failed differentiation program that leads to tubule atrophy needs investigation. 146

148 58 Renal Angiogenesis and Inflammatory Mediator Patterns Differ in Murine Models of Sepsis and VILI Mark L Hepokoski 1, Joshua A Englert 2, Rebecca M Baron 3, Laura E Crotty-Alexander 1, Mark Fuster 1, Jeremy Beitler 1, Atul Malhotra 1, Prabhleen Singh 1 1 University of California San Diego School of Medicine, 2 The Ohio State University, Wexner Medical Center, 3 Brigham and Women's Hospital, Boston, MA PURPOSE: Acute respiratory distress syndrome (ARDS) that leads to acute kidney injury (AKI) carries a mortality of 58% compared to 28% in ARDS alone. There are roughly 190,000 new cases of ARDS in the United States each year, and AKI is twice as likely in these patients. Many of the potential etiologies of AKI in ARDS may stem from consequences of mechanical ventilation on the kidney, as ARDS patients often require mechanical ventilation as a life saving intervention. Injurious mechanical ventilation in ARDS may lead to the release of inflammatory mediators from the lung via ventilator induced lung injury (VILI), and these mediators may have detrimental effects in the kidney. This process is termed, biotrauma. The purpose of this study was to gain mechanistic insight into the mediators involved in lung to kidney biotrauma by comparing protein expression changes in the kidneys of mice exposed to VILI with, and without sepsis. We hypothesized that biotrauma related to VILI would have a unique renal inflammatory pattern compared to sepsis induced by cecal ligation puncture (CLP) and CLP with VILI. METHODS: C57BL/6 wild type mice underwent either CLP (23g, 1 hole, 100%) or sham operation 24 hours prior to mechanical ventilation (or spontaneous breathing control) with 20cc/kg tidal volumes for 4 hours using a Flexivent rodent ventilator. Tissue lysates from harvested whole kidneys were prepared from each group, and protein expression analyzed using a proteome array (mouse XL cytokine array, R&D Systems). The team performing the array analysis was kept blinded to the etiology of each sample. RESULTS: Markers of septic tubular injury, such as NGAL and TNF-alpha, were significantly increased in both CLP groups compared to control and VILI without sepsis (Figure 1). VILI with and without CLP led to increased levels of vascular endothelial growth factor (VEGF). Proteins involved in the Angiopoetin/Tie2 axis, such as angiopoetin-2, were not remarkably increased in CLP or VILI samples alone, but there was significantly increased expression in the CLP with VILI group. CONCLUSION: Angiopoetin-2 is a known mediator of endothelial leak, and persistently elevated levels have been associated with kidney injury in sepsis and ARDS. VILI may be a mechanism of increased renal angiopoetin-2 in mechanically ventilated patients with sepsis. Further research is necessary to determine the potential role of VILI induced angiopoetin-2 as a cause of AKI in sepsis induced ARDS. Figure on following page 147

149 59 The Prognostic Value of the Furosemide Stress Test in Predicting Delayed Graft Function Following Kidney Transplantation. Blaithin A McMahon 1, Jay L Koyner 2, Tessa Novick 1, Edward Kraus 1, Niraj Desai 1, William T Merritt 1, Promise Ariyo 1, Lakhmir S Chawla 3, Bonnie E Lonze 1 1 Johns Hopkins Hospital, 2 University of Chicago, 3 Washington DC Veterans Affairs Medical Center Background: The Furosemide Stress Tess (FST) is a novel dynamic assessment of tubular function that has been shown in preliminary studies to predict patients who will progress to advanced stage Acute Kidney Injury, resulting in the need for renal replacement therapy in a substantial proportion of patients. Aim: To investigate if the urinary response to a single intraoperative dose of furosemide predicts delayed graft function (DGF) in patients undergoing kidney transplant (KT). Methods: This was a single center retrospective cohort analysis of patients undergoing KT from 01/2010 to 06/2015. As standard of care at Johns Hopkins Hospital, all patients undergoing KT receive a single dose of intraoperative furosemide after the anastomosis of the renal vessels and their urine output (UO) is measured hourly via a Foley catheter. Inclusion criteria for the study were: 1) KT, 2) age 18 years, 3) patients who received a 100mg of furosemide intraoperatively. Clinical variables were obtained from the institutional transplant database. DGF 148

150 was defined as the need for renal replacement therapy (RRT) within 1 week of KT. UO was evaluated at 2 and 6hrs post renal vessel anastomosis. Multiple logistical regression (MLR) analysis was used to predict DGF based on different values for UO at 2 and 6hrs. Area under the receiver operator curves (ROC) that predicted DGF for different values of UO at 2 and 6hrs were calculated. Both the MLR and the ROC were adjusted for age, race and gender. Results: A total of 803 patients met the inclusion criteria. Preliminary analysis of a random subsample of 200 patients was performed. The mean age was 52.9 ± 13.7 years, 41% were male, 51% were African American, 38% were white and 11% were other race. The UO associated with the greatest odds ratio (OR) and AUC at 2 and 6hrs were, 150mls and 600mls, respectively. The adjusted OR for DGF in patients who had a UO of 150mls compared to patients who had a UO of < 150mls at 2 hours was 9.57 (95% CI: , p<0.001). The adjusted OR for DGF in patients who had a UO of 600mls compared to patients who had a UO of <600mls at 6 hours was (95%CI: , p<0.001). The AUC for DGF based on a UO of <150mls at 2 hours was 0.78 (95%CI: ). The AUC for DGF based on a UO of <600mls at 6 hours was 0.80 (95%CI: ). Conclusion: The FST is a predictor of DGF post KT and has the potential to identify patients requiring RRT early after KT. 149

151 RRT TECHNIQUE CHARACTERISTICS 60 Cost Analysis Of Standardizing CRRT Processes Salma Elbehary 1, Steven Hays 1, Katy M Cox 1, Sean Ramsey 1, Harold M Szerlip 1 1 Baylor University Medical Center, Dallas, TX, USA Purpose of the study: Acute Kidney Injury in the ICU has been increasing in incidence over the last decade. It has been estimated that approximately 5% of patients admitted to an ICU require renal replacement. Because of hemodynamic instability and need for volume removal, continuous therapies (CRRT) have become the procedure of choice. Because of decreasing reimbursement it is essential that healthcare systems maximize cost efficiency. We therefore analyzed the cost savings of changing from a single dialysate solution that was tailored to the patients needs to using multiple different solutions. Methods: Baylor University Medical Center operates 118 ICU beds and performs approximately 220 CRRT treatments a month. Because of storage issues we purchased only 0 meq K+ dialysate (NxStage- RFP-402) and added electrolytes as needed. In September 2015 we began purchasing premixed 2 and 4 meq K+ solutions and except in exceptional cases supplemented Mg, PO4 and HCO3 peripherally. We analyzed labor and material costs during a one month period and then estimated the costs for 12 months. Total costs were calculated and included wasted bags, compounding costs and labor costs divided between pharmacist and pharmacy technician.. Results: Annualized over a 1 year period approximately 48,500 five-liter bags were dispensed. Preparation time for six 5-liter bags declined from 25.5 minutes in the old system to 12 minutes in the new. 67 bags were discarded because they were compounded but never used. In addition to the cost of wastage, 12 minutes were required to process each wasted bag. Over a 12 month period it estimated that we will save $469,879 in labor and material costs. Conclusion: By changing our practice we will be able to produce a significant cost savings without jeopardizing quality. In fact by eliminating compounding we have removed a possible source of error. Because of this we have changed our purchasing practice, revised our CRRT order set, educated our prescribers on decreasing unnecessary additives and enhanced patient safety. 150

152 61 The comparison of double lumen temporary hemodialysis catheter and tunneled cuffed hemodialysis catheter on vascular access of continuous renal replacement therapy Dongyeol Lee 1, Hansae Kim 1, Jin Ho Lee 1, You Jeong Oh 2, Joon-Seok Oh 1, Seong-Min Kim 1, Yong-Hun Sin 1, Joong-Kyung Kim 1 1 Bongseng memorial Hospital, Busan, Korea, 2 Department of Internal Medicine, Dong-Eui Medical Center, Busan, Korea Objective: A vascular access is needed for performing continuous renal replacement therapy (CRRT). The type of vascular access in the most case is temporary and permanent catheter in intensive care unit. But double lumen temporary hemodialysis catheter is occurred more catheter malfunction and filter clotting more than permanent catheter. Therefore, we retrospectively evaluated which vascular access may affect filter life during CRRT. Method: We evaluated 44 patients with acute kidney injury requiring CRRT from March 2014 through October patients used double lumen temporary hemodialysis catheter and 22 patients used tunneled cuffed hemodialysis catheter. All catheters were inserted in the internal jugular position. We obtained age, gender, duration of CRRT, number of use of CRRT filter, dose of anticoagulation. Result: The mean durations of CRRT were 3.77 ± 2.67 days, mean ages were ± years, number of use of CRRT filter was 1.02 ± 0.37 / day, nafamostat mesilate which is anticoagulant was ± 5.44 mg / hour in double lumen temporary hemodialysis catheter groups. The mean durations of CRRT were 5.31 ± 6.09 days, mean ages were ± 6.76 years, number of use of CRRT filter was 1.18 ± 0.37 / day, nafamostat mesilate was ± mg / hour in tunneled cuffed hemodialysis catheter. Conclusion: Tunnel cuffed hemodialysis catheter is less occurred CRRT filters clotting and less needed anticoagulation. 62 Using a Bridging Technique for Continuous Renal Replacement Therapy Circuit Change Reduces Time off Therapy and Exposure to Blood Products Rebecca Greene 1, Vimal Chadha 1, Gianna Swift 1 1 Children's Mercy Hospital, Kansas City, MO, USA Introduction: Continuous Renal Replacement Therapy (CRRT) is the preferred method of dialysis for critically ill pediatric patients with acute renal failure. Manufacturers recommend changing the CRRT circuit every 72 hours to ensure the integrity of the tubing and support adequate flow rates. This necessitates a circuit change for patients requiring therapy longer than three days. However, some circuits show signs of failure prior to the end of 72 hours. Circuit changes traditionally resulted in the patient being without therapy for over an hour. In addition, the circuit set up for neonates and infants requires a blood prime due to the large extra-corporeal circuit volume. 151

153 Methods: Our institution implemented a new circuit changing procedure (bridging) in 2013 to rapidly exchange CRRT circuits and reduce blood exposure as described by Yorign et al. Bridging is the preferred method for patients who are hemodynamically unstable, require a blood prime, or are showing signs of clotting. Bridging includes setting up a separate circuit with new filter and tubing. All routine aspects to set up the pump are performed. During this time, the patient is still on their old circuit, receiving CRRT therapy as ordered. Once the new circuit is ready, the old circuit is stopped and the patient s dialysis catheter is flushed and packed. The old circuit is then connected to the new circuit and rinsed so that the blood from the old circuit is flushed into the new circuit. Then the patient is re-accessed and connected to the new circuit and therapy is restarted. This method requires the use of two CRRT pumps and two staff members trained on the procedure. Results: Since 2013, 220 circuits have been changed. Of those, 59 were done so by bridging. The most common reason for bridging was to avoid a blood prime, of the 220 circuits 99 of them would have required a blood prime, and we bridged 43 of those. The time required for a circuit change by bridging (6.3 ± 3 min) was significantly (p<0.05) less than for traditional circuit changes (58 ± 14 min). The process of bridging was also well tolerated except on only one occasion. In contrast, significant hemodynamic events (hypotension, bradycardia) were seen in 19% of patients when the circuit was changed by conventional method. Conclusion: Bridging exchange of the CRRT circuit is a safe and efficient method that significantly reduces exposure to blood products, therapy downtime, and hemodynamic instability. 63 Underutilization of Citrate Anticoagulation for Continuous Renal Replacement Therapy: A Survey Study Lindsay Sanders 1, Ayan Sen 1, Mira T Keddis 1 1 Mayo Clinic Arizona Purpose: Citrate use as an anticoagulant for the continuous renal replacement therapy (CRRT) circuit has been shown to improve safety and efficacy of CRRT and lead to overall decreased cost compared to heparin. While widely acknowledged to be an excellent extracorporeal regional anticoagulant, the routine use of citrate for CRRT has been limited. The purpose of this study is to investigate practice patterns and barriers to utilization of citrate for anticoagulation for CRRT among key stakeholders in an intensive care unit (ICU) in a single center. Methods: Three survey questionnaires were created on REDCap and sent to a sample cohort of physicians and advanced practitioners, critical care nurses, and ICU pharmacists via from September-November Three follow-up s were sent after the initial invitation. For statistical analysis, Microsoft Excel 2010 (Microsoft Corporation, Redmond, VA) was used. Results: Nearly half (44.6%) of all those invited to participate responded: 59.2 % (16/27) of physicians and advance practice providers, 40.9% (63/154) of nurses, and 100% (3/3) of pharmacists. There was significant difference regarding preference for heparin/no anticoagulation approaches compared to use of citrate. Fortyfour percent of nurses preferred heparin versus only 13% who indicated preference for citrate (p<0.05). Physicians and advanced practice providers [31.2% for citrate compared to 68.8% for heparin/no anticoagulation (p<0.05)] and pharmacists [0% for citrate versus 100% for heparin or no anticoagulation (p<0.001)] also revealed a similar bias. The most commonly cited reasons for the preference of heparin included 152

154 ease of use and familiarity with heparin (25 respondents) and difficulty monitoring and managing abnormal laboratory values with citrate (8 respondents). Conclusions: Our surveys indicate that a significant number of physician and advanced practice providers, nurses, and pharmacists in the ICU are uncomfortable using citrate for regional anticoagulation during CRRT. Given the known risks associated with systemic heparin, increased association with dialysis filter clots, and low risks associated with citrate use, further educational efforts and quality improvement initiatives are needed to address citrate under-utilization for CRRT in ICU settings. 64 CRRT Without Anticoagulation. Feasibility and Prescription Factors. Armando Vazquez-Rangel 1, Gabirela Hernandez 2, Alberto Santos 2, Jose Carlos Pena 2 1 Instituto Nacional de Cardiologia, 2 Centro de Diagnostico Angeles INTRODUCTION: Filter coagulation is the most frequent complication during CRRT, leading to a lower delivered dose, blood loss and increased costs. On the other hand, avoiding heparin in order to reduce bleeding complications is justified, but when no citrate is available then CRRT without anticoagulation might be considered in our short experience. METHODS: An observational cohort study analyzing filter life-span was carried out during CRRT in patients admitted into mixed ICUs in private hospitals in Mexico City from March to October Patient treatments were included if they fulfilled the following criteria: acute kidney injury, severe sepsis or septic shock, no systemic anticoagulation, no use of citrate anticoagulation, no new surface treated membranes. Usually, there is a trend towards avoiding the use of heparin; in case of losing a filter in less than 24 hours, and no citrate is available, then heparin is started in the next filter. There was no routine use of flushes or recirculation strategies to avoid clotting. We describe filter life-span up to clotting or clogging in filters without anticoagulation, compared to heparin, and we analyzed some prescription specifications that allowed running this treatment without anticoagulation. RESULTS: A total of 85 filters from 31 patients were analyzed, 28 filters (32.9%) with heparin and 57 (67.1%) without anticoagulation. In general, most common prescription was pre-dilutional CVVHDF, blood flow was 180 ( ), pre-dilutional replacement flow as 67% (61-72) of total dose, pos-dilutional replacement flow as 9% (0-9), and dialysate flow as 23% (12-28) of total dose. Median filter survival with heparin was 72 hours vs 38 hours without anticoagulation (Log rank 1.65, p=0.099). In filters treated without anticoagulation, a filtration fraction <0.175 had a significant benefit on filter life-span (Log rank 2.23, p=0.025). Due to a low number of pure CVVH treatments, only a non-significant trend towards increase filter life-span with use of higher dialysate flow was observed. CONCLUSIONS: CRRT without anticoagulation is feasible under certain prescription factors, if heparin should be avoided and citrate is not available. Figure on following page 153

155 154

156 RRT APPLICATIONS AND TARGETED INTERVENTION 65 Influence of Daily Fluid Balance prior to Continuous Renal Replacement Therapy on Outcomes in Critically Ill Patients Jung-ho Shin 1, Min Jee Han 1, Ki Hyun Park 1, Su Hyun Kim 1 1 Chung-Ang University Hospital, Seoul, Korea Background: Positive fluid balance is a risk factor for mortality in critically ill patients, especially those requiring renal replacement therapy. However, it remains unclear whether daily fluid balance is associated with various organ impairments, which can influence worse outcomes. The present study investigated the impacts of daily fluid balance prior to continuous renal replacement therapy (CRRT) on organ dysfunction, as well as mortality in critically ill patients. Methods: We recruited 100 patients who experienced CRRT, and identified the daily fluid balance between ICU admission and CRRT initiation. The time to CRRT initiation and 28-day mortality were evaluated. Furthermore, organ failure based on the sequential organ failure assessment (SOFA) score was also assessed according to daily fluid balance. Results: Included patients were followed for a median of 10 [3, 26] days, and CRRT was initiated within 2 [0, 4] days. The time to the start of CRRT was shortened in proportion to daily fluid balance (P = 0.001). This result was persistent after the adjustment for age, gender, and the renal SOFA score at ICU admission (HR 1.14, 95% CI 1.04 to 1.25, P = 0.007). The prevalence of respiratory, cardiovascular, and nervous failure was increased in patients with excessive positive fluid balance (P = 0.075, and 0.004, respectively). Moreover, positive daily fluid balance was a risk factor for respiratory, cardiovascular, nervous, and coagulation failure, independent of age, gender, and each organ SOFA score at ICU admission (HR 1.36, 1.26, 1.24 and 1.38, all P < 0.05). We found that positive fluid balance increased the rate of 28-day mortality, independent of age, gender, and the baseline SOFA score (HR 1.14, 95% CI 1.01 to 1.25, P = 0.007). Conclusion: This study found that positive daily fluid balance prior to CRRT may not only accelerate the requirement for CRRT but could also increase the risk of multiple organ failure as well as mortality in critically ill patients. Therefore, judicious fluid therapy should be performed in critically ill patients, especially those requiring CRRT. Further studies to elucidate the protective effects of restrictive fluid therapy on multiple organ systems and mortality are needed. 155

157 66 Use of Segmental Bioimpedance Analysis in Critically Ill Patients requiring Continuous Renal Replacement Therapy Jung-ho Shin 1, Ki Hyun Park 1, Jin Ho Hwang 1, Su Hyun Kim 1 1 Chung-Ang University Hospital, Seoul, Korea Background: Fluid overload prior to continuous renal replacement therapy (CRRT) is an important prognostic factor. Accordingly, precise evaluation for fluid status is necessary to treat critically ill patients. In this study, we investigated whether fluid assessment using bioimpedance analysis (BIA) can predict outcomes in critically ill patients requiring CRRT. Methods: A prospective observational study was performed between Mar 2014 and Dec Patients who admitted in the intensive care unit and required CRRT were recruited. Segmental BIA was conducted before CRRT in included patients to obtain the total and segmental ratio of extracellular water to total body water (ECW/TBW). Results: A total of 35 patients treated with CRRT were included in the study. There were 23 (65.7%) men and 12 (34.3%) women, and the median age was 71 [47, 80] years. Of included patients, 20 (57.1%) were survived after treatment. Among the total and segmental ECW/TBW, that of right arm was correlated with levels of hematocrit, total protein, albumin and C-reactive protein, and total SOFA score (P = 0.083, 0.086, 0.030, and 0.055), however, was not associated with levels of erythrocyte sedimentation rate, procalcitonin, 25-vitamin D and lactate. Survivors showed low levels of ph and total protein, and high levels of lactate and right arm ECW/TBW, compared with non-survivors (P = 0.021, 0.039, and 0.033). Receiver operating characteristics (ROC) curve was constructed for ECW/TBW for predicting mortality. The ECW/TBW of right arm had an area under the curve (AUC) of 0.71 (95% CI 0.54 to 0.89, P = 0.033), on the other hand, the total and the other segmental ECW/TBW did not have significant AUCs for mortality. Conclusion: Fluid status can be assessed using segmental BIA in critically ill patients requiring CRRT, moreover, it may predict poor outcomes, especially with the result from right arm. To confirm the usefulness of segmental BIA for predicting outcomes in critically ill patients, further large studies are needed. 156

158 67 Unusual and no renal indications for continuos renal replacement therapy (CRRT) Jesus Mier 1, Víctor Castañeda 1, Arizpe Daniel 1, Eduardo Marín 1, Rachid Cesin 1, Samuel Vargas 1, Leonor Rivera 1 1 Hospital Angeles Puebla Latest publications have demonstrated that The CRRT is successful in orgánic failure from different etiologies to the renal one,such as venous congestive heart failure,poisonings,hepatic,pulmonary failure and sepsis between others.the aim of this article is to show our experience,with a group of 13 patients that were admitted to our Unit with diagnóstic and indications unusuals for having CRRT.table1 Method and Materials We received 13 patients (6 m and 7 w),2 of them with hepatorenal failure,2 with Congestive HeartFailure,5 with sepsis and the last 6 with other patologíes.all patients were submitted to the modality (CVVDHF)with liquid remplacement Prisma Sate BGK 4/2.5 in predilution with replacement of 30 ml/kg,giving and average result of 30 liters.the therapy was carried out with a Prisma Flex Plus Gambro machine,with ST150 filter with membrane AN 69 HF.Heparine was use as Necessary.All the patients complete at least a mínimum period of 24 hours and 30 percent 48 hours,according todo the severity of cases seizure by SOFA (Sequential Organ Failure Assesment). Results From 13 patients,10 of them(76.9%) survive and were discharged from hospital,3 patients(23.1%)( 2 w and 1 M) were dead. In groups 1,3 and 4 were dead 1 in each group.those patients that were dead had a SOFA clasification moré than 3.Independently of the cause of dead,all patients achieve and important level decrease in azoemia,although in this group of patients the main objective was to lower sustances dificultt to detect ( Piggy) In patients with cardiac failure we achieved ultra filtrations above 15 liters without hemodynamic instability or imbalance.despite is a small group of patients,all of them carry pathologies were Clinics and no creatinin leves are the final predictors. Conclusions 1. The continuous replacement therapy is efectivo in other pathologies different from The renal one. Specially in those patients with fluid overload. Independently of creatinin levels 2. La CVVDHF is the most common method used,because is easilly reproducible in other hospitals to increase our knowledge in this kínd of patients 3. The survival as group was bigger than the reports in literature for patients with similar SOFA 4. The ICU and hospital stay was lesser than the average with similar score 5. Mortality is associated to delayed treatment 6. We concluded that this kínd of therapy should be investigated deeply and compare control groups in hospitals with other modality of replacement therapy Table on following page 157

159 NAM E SE X A G E DX # SESIONS JCF M 84 ANASARCA 1 10 LLP F 64 PANCREATIT IS/HEPATO RENAL FAILURE AAA M 78 SEPSIS/PACE MAKER SDM M 76 EVC/ANASAR CA JLA M 80 SEPSIS 3 0 ETA M 44 ALA F HEPATO RENAL FAILURE 54 POISONING/A NASARCA GJB F 34 SEPSIS 1 0 RER F 74 TAB LE 1 CVV HDF 116/9 6 NO 12 ID 18 ID Y ES Y ES B V C G C X SEPTIC SHOCK/ANAS ARCA 1 8 LITER S REM OVED DA TE 16/0 2/15 31/0 5/15 08/0 5/15 11/0 5/15 09/0 6/15 19/0 6/15 03/0 7/15 30/0 6/15 23/0 6/15 57/ 40 1/.8 12/12 NO GH L N O 96 M F ANASAR CA/CHF 1 20 MODA LITY CVVH DF CVVH DF CVVH DF CVVH DF CVVH DF CVVH DF CVVH DF CVVH DF CVVH DF RESPO NDERS UREA IN/EN D CREAT IN/END YES 75/52 1.8/1.6 YES 201/ /2.7 NO 105/79 3.8/3.2 YES YES 97.8/ / / /1 YES 160/80 2/1.6 NO 213/ /3 YES 33/31.95/.53 NO F 34 08/08/1 4 CVVHD F CVVH DF GUILLEA N BARRE 1 F DCC 5 ID 12/17/ 14 LES/ANA SARCA /04/1 5 CVVHD F ID = INTRAHOSP ITALARY DAYS HB OT HER 15. 8/1 6 16/ 16 14/ / / /1 0 10/ 10 12/ / 10 NO BT 39/3 3 NO NO NO BT 36/ ID NO.75/. 6 SEPSI S/LES /0 9/14 YES 60/50 103/70 1.2/ / /70 1.7/.5 9/9 0 13/1 2 13/

160 68 Extracorporeal Ultrafiltration Therapy for Acute Decompensated Heart Failure Negiin Pourafshar 1, Ashkan Karimi 1, Amir Kazory 1 1 University of Florida, Gainesville, Florida, USA Background: There has been a renewed interest in the use of ultrafiltration (UF) for management of patients with acute decompensated heart failure (ADHF). While a number of studies reported on the efficacy of this therapy and lack of any significant adverse impact, the more recent trials have challenged its safety. The aim of this study is to provide a reappraisal of the current evidence on the use of UF in ADHF. Methods: Articles cited in PubMed database from 2000 to 2015 using key words ultrafiltration and heart failure were searched. Those randomized and non-randomized trials using recent portable devices dedicated for UF were selected. Case reports, and case series were excluded. Relevant data such as renal function, cardiac status, and weight change were extracted and compared. Results: A total 940 patients from 15 trials (7 randomized and 8 non-randomized) that used dedicated UF devices were included. Eleven studies reported either no change or non-significant decrease in serum creatinine, while 4 found worsening renal function after UF therapy; these studies had included patients with more severe renal dysfunction at baseline. Concerning weight, a reduction of 2 to 9 Kg was reported that was similar to conventional therapies in 9 studies but was significantly lower with UF in 6 trials. Length of stay was evaluated in 5 studies, 2 of which showed a significant reduction. Three studies showed fewer re-hospitalizations in the UF group at 30 days, 90 days, and 1 year follow ups. None of the studies evaluated long-term outcomes of patients undergoing UF therapy. Conclusion: Based on the currently available data, UF is efficient for management of volume overload in ADHF. However, these studies do not support any beneficial impact for this therapy on renal function, and suggest that it might be associated with suboptimal renal outcomes if used for patients with more severe renal dysfunction at baseline. Currently there is no data on the effect of UF on long-term outcomes of patients with ADHF. Whether this would translate into a lack of effect for UF on these outcomes needs to be elucidated by future studies. 69 The Assessment of Volume Status by Bioelectrical Impedance Analysis and Lung Ultrasound in Septic AKI Patients Undergoing CRRT Youn Kyung Kee 1, Seohyun Park 1, Seung Gyu Han 1, Jung Tak Park 1, Seung Hyeok Han 1, Tae-Hyun Yoo 1, Shin-Wook Kang 1 1 Department of Internal Medicine, College of Medicine, Yonsei University Purpose: Septic acute kidney injury (AKI) is one of the most common causes in critically ill patients requiring continuous renal replacement therapy (CRRT). The fluid status of the patient is known as significant risk factor in those patients. Thus, it is necessary to find an objective assessment of volume status. The aim of present study is to elucidate the impact of fluid status assessment by bioelectrical impedance analysis (BIA) and lung ultrasound (US) in septic AKI patients with CRRT. Methods: A single center prospective observational study was conducted between April 2014 and February We included 39 septic AKI patients undergoing CRRT in ICU. BIA and lung US were performed at the 159

161 time of CRRT initiation. We classified patients into two groups followed by survivor and non-survivor. We measured over-hydration (OH) values in BIA and number of B-lines in lung US. Primary endpoint was 28-day mortality. Logistic regression analysis was used to evaluate the risk factors affecting 28-day mortality. Results: The mean age was 64.6 ± 14.1 years and 24 (61.5%) was male. The median follow up was 29 days. During the study period, 19 deaths (48.7%) occurred. Survivor group showed significantly lower weight gain, which was defined as a body weight difference from that of last visit, at CRRT initiation (2.0 ± 3.5 vs. 5.8 ± 5.5, P = 0.017) and APACHE2 score (21.7 ± 5.3 vs ± 1.5, P = 0.006) compared with non-survivor group. However, there was no significant difference in results of BIA and lung US between both groups. OH per body mass index (BMI) measured by BIA had significant correlation with mean arterial pressure (r = , P = 0.034) and NT-pro BNP (r= , P = 0.024), and B-line measured by lung US had significant correlation with APACHE2 score (r = 0.330, P = 0.040). Logistic regression analysis showed a trend that increasing OH per BMI (odds ratio (OR) 6.18, 95% confidence interval (CI) , P = 0.334) and number of B-lines (OR 1.14, 95% CI , P = 0.458) were associated with increasing risk of 28-day mortality, but there was lack of statistical power. Conclusion: In this study, we found that OH status assessed by BIA and lung US correlated with traditional risk factors on poor clinical outcomes in septic AKI patients with CRRT. In addition, this study showed the association between OH per BMI measured by BIA and number of B-lines measured by lung US and 28-day mortality rate in critically ill patients undergoing CRRT. 70 Development of Ciprofloxacin Dosing Recommendations for Critically Ill Patients Receiving SHIFT Renal Replacement Therapy Alex R Shaw 1, Susan J Lewis 1, Weerachai Chaijamorn 1, Bruce A Mueller 1 1 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Background: Ciprofloxacin is an antibiotic commonly used in the intensive care unit where acute kidney injury (AKI) is prevalent. SHIFT is a daily 8-10 hour prolonged intermittent renal replacement therapy that is growing in popularity. However, a lack of antibiotic dosing information in critically ill patients receiving SHIFT limits its use. The purpose of this study was to use Monte Carlo Simulations (MCS) to develop ciprofloxacin dosing recommendations for SHIFT. Methods: Using previously-published pharmacokinetic & demographic data from critically ill patients, a population PK model was developed for SHIFT RRT. A series of 5000-subject MCS were performed for four shift regimens with varying duration (8 & 10 hr), effluent rate (4 & 5 L/hr), modality (HF/HD), and time of SHIFT initiation relative to ciprofloxacin administration. Ciprofloxacin regimens were evaluated on the probability of attaining a total drug concentration resulting in a ratio of area under the curve to minimum inhibitory concentration (MIC) 125 during the first 72 hours of therapy. Optimal regimens yielded a probability of target attainment (PTA) 90% for sensitive Pseudomonas aeruginosa (MIC=1mg/L) using the smallest total daily dose. Results: Intravenous ciprofloxacin administered as a 1200mg loading dose and a maintenance dose of 800 mg every 12 hours was the smallest daily dose to yield a PTA 90% in all SHIFT settings for MIC values 1. (See Figure). No FDA-approved ciprofloxacin dosing recommendations for any population reached the PTA 90%. 160

162 Conclusions: In critically ill patients receiving daily 8 or 10 hour SHIFT, the lowest possible ciprofloxacin dose to meet 90% PTA was 1200mg LD and 800 mg every 12 hours, but this high dose is likely to be cardio- or neurotoxic. The use of ciprofloxacin in critically ill patients receiving SHIFT cannot be recommended as monotherapy for Gram negative infections. 71 Monte Carlo Simulations (MCS) to Determine Optimal Levofloxacin Dosing for Gram Negative Infections in Patients Receiving SHIFT RRT Weerachai Chaijamorn 1, Susan J Lewis 2, Alex R Shaw 2, Bruce A Mueller 2 1 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA: Faculty of Pharmacy, Siam University, Bangkok, Thailand, 2 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Background: SHIFT is a daily 8-10 hour renal replacement therapy (RRT) for treating acute kidney injury in critically ill patients. Antibiotic pharmacokinetic data in SHIFT are lacking. At higher quinolone doses, cardioand neurotoxicity can occur; doses are recommended to be reduced in renal disease. This study evaluated the likelihood of attaining levofloxacin exposures that correlate with antibiotic efficacy known as probability of target attainment (PTA). Methods: Published levofloxacin pharmacokinetic data in critically ill patients were used to develop models for virtual patients receiving daily SHIFT with intermittent hemofiltration (HF) or hemodialysis (HD). Eight models were developed to account for the SHIFT variations including duration (8 and 10 hr), effluent rate (4 and 5 L/hr), modality (HF/HD), and time of SHIFT relative to drug dose. MCS generated drug concentration 161

163 profiles for each regimen in a different group of 5,000 virtual patients. The pharmacodynamic (PD) target was > 125 for area under the concentration-time curve to the minimum inhibitory concentration (MIC) of 2 mg/l (MIC for sensitive Pseudomonas aeruginosa) for the initial 72 hours of therapy. The optimal regimen required > 90% of PTA for this drug with the lowest daily doses to decrease toxicity risk. Results: The attainment of > 90% of PTA required levofloxacin doses of >3,000 mg/day (Figure) in all 8 SHIFT models. Desired PTA could not be achieved by using the FDA-approved doses. A regimen with an extremely high loading dose and post-shift dosing were the only regimens found to yield a PTA of 90%. Conclusion: A levofloxacin dose of 2,000 mg loading dose with 1,000 mg q 24 hours post-shift achieved the PTA for all SHIFT settings, but this regimen is likely to be toxic. No conventional levofloxacin doses could achieve 90% PTA. Using levofloxacin in patients with SHIFT RRT cannot be recommended as monotherapy for Gram negative infections. 162

164 72 Monte Carlo Simulations (MCS) to Determine Optimal Levofloxacin Regimens for Streptococcus pneumoniae Infections in Patients Receiving SHIFT Renal Replacement Therapy. Weerachai Chaijamorn 1, Susan J Lewis 2, Alex R Shaw 2, Katherine N Gharibian 2, Bruce A Mueller 2 1 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA: Faculty of Pharmacy, Siam University, Bangkok, Thailand, 2 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Background: SHIFT is a daily 8-10 hour renal replacement therapy (RRT) for treating acute kidney injury in critically ill patients. A levofloxacin dose of 500 mg q 48 hours has been recommended for patients receiving continuous RRT, however levofloxacin pharmacokinetic (PK) data in SHIFT does not exist. Precise levofloxacin dosing is important because cardio- and neurotoxicity of higher doses have been reported and dosage reduction in renal disease patients is recommended. The purpose of this study was to use MCS to determine appropriate levofloxacin doses for S. pneumoniae infections in SHIFT. Method: Pharmacokinetic models were developed using published demographic/pk data in critically ill patients with known variability and limits. Four daily-shift settings (hemofiltration or hemodialysis with effluent rates of 5L/hour x 8 hours or 4L/hour x 10 hours) occurring at 2 different times relative to levofloxacin dose were modeled. A set of 5,000 virtual patients was created and tested for each dosing regimen. The pharmacodynamic (PD) target was > 50 for area under the concentration-time curve to the minimum inhibitory concentration (MIC) of 2 mg/l (MIC for sensitive S. pneumoniae) for the initial 72 hours of therapy. The optimal regimen required > 90% of PTA for this drug with the lowest daily doses to decrease toxicity risk. Results: Levofloxacin administered as a loading dose of 750 mg with 500 mg q 24 hours post-shift yielded a PTA > 90% in all 8 SHIFT settings. Conclusion: Levofloxacin 750 mg loading dose with 500 mg every 24 hours post-shift is recommended in acute kidney injury patients receiving SHIFT RRT who have S. pneumoniae infections. Levofloxacin doses for Gram negative infections that have higher PD targets will require much higher doses. PK validation studies for these findings are required. 163

165 73 Slow Continuous Ultrafiltration Efficiently Improves Congestion in Acute Heart Failure without Adverse Impact on Renal Function: a Meta-analysis Ankur Jain 1, Nikhil Agrawal 1, Amir Kazory 1 1 University of Florida Background: Diuretic-based conventional regimens of acute decompensated heart failure (ADHF) are commonly associated with suboptimal results. There has been a renewed interest in the use of slow continuous ultrafiltration (SCUF) for management of fluid overload in these patients. While a number of studies reported on the efficacy of this therapy in improvement of congestion, recently there has been concern about its safety. The aim of this meta-analysis is to provide a reappraisal of the current evidence on the impact of SCUF on fluid removal, weight loss, and renal function in the setting of ADHF. Methods: Articles cited in PubMed, EMBASE, and Cochrane database from 1980 to 2015 using key words: ultrafiltration and heart failure were searched and those randomized controlled trials (RCTs) that addressed the role of SCUF in ADHF as compared with conventional therapy were identified. A total of 289 studies were selected after extensive database search. A meta-analysis was performed. Mantel-Haenszel random-effects model was used to calculate mean differences (MDs) with 95% confidence intervals (CIs). Comprehensive meta-analysis software version 3 was used for the analysis. Results: After excluding duplicate, non-randomized, and studies not relevant to the primary question, a total of 7 RCT with 768 participants were found eligible for analysis. Fluid removal and weight loss were considered as efficacy endpoint and change in renal function as the safety endpoint. Fluid removal was significantly higher with SCUF compared to standard therapy, MD of 1.81 L (95% CI , p<0.01). It also led to higher net weight loss, MD of 1.38 Kg (95% CI ,p<0.01). However, the MD for change in in serum creatinine was 0.06 mg/dl and was not statistically significant (95% CI; , p=0.48). Conclusion: Currently available data suggest that compared to diuretic-based therapy, SCUF improves congestion in ADHF more efficiently as evidenced by greater fluid removal and weight loss without portending a notable adverse impact on their renal function. Tables on following page 164

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167 NEW TECHNOLOGY 74 Outside-In Hemofiltration For Prolonged Operation Without Clogging - Hydrodynamics, Filter Designs and Challenges MOHAMED E LABIB 1, STANISLAV S DUKHIN 1, YACOOB TABANI 1, RICHARD LAI 1, OMAR A LABIB 1, ANDREW L ZYDNEY 2 1 NOVAFLUX TECHNOLOGIES, 2 The Pennsylvania State University, Dept. of Chemical Engineering, University Park, PA Hemofiltration (HF) is used extensively for continuous renal replacement therapy (CRRT), but long-term treatment is limited by thrombosis leading to fiber clogging. Maximum filter life in CRRT is typically less than 20 hours. For the first time in the field, we have achieved continuous and consistent hemofiltration for more than 100 hours using outside-in hemofiltration with the blood flow into the inter-fiber space (IFS) with minimal increase in filter pressure. Although thrombi do deposit in the IFS, they have minimal affect on the blood flow and filtrate flux due to the three-dimensional system of interconnected hydrodynamic flow channels in the IFS. Microscopic examination of sections of the fiber bundle showed that deposited thrombi have dimensions about the size of the gaps between the hollow fibers and remain isolated from each other. Mathematical models have been developed to describe the effect of thrombi deposition on the fluid flow which accounts for the enhanced filter performance arising from the interconnected flow. The hydrodynamic advantage of outside-in HF technology is expected to minimize the need for complex anticoagulation systems like regional citrate anticoagulation (RCA). For successful uninterrupted blood processing with the new outside-in HF technology, new filter configurations and designs are required. These results clearly demonstrate the significant potential advantages of using outside-in hemofiltration for long-term CRRT and for other extracorporeal therapies including hemodialysis and hemodiafiltration. The advantages, disadvantages and challenges of this new technology will be elaborated. Details of applications in both acute and chronic therapies will be presented. 166

168 75 Extracorporeal Carbon Dioxide (CO2) Removal with Continuous Renal Replacement Therapy - A Novel Therapy Sachin Gupta 1, Deepak Govil 1, Shrikanth Srinivasan 1, Jagadeesh KN 1, Sweta J Patel 1, Anand Gupta 1, Deeksha S Tomar 1, Parmender Shokeen 1, Dinesh K Agarwal 1, Mozammil Shafi 1 1 Medanta The Medicity Introduction: Acute respiratory distress syndrome (ARDS) with renal failure is a common phenomenon in ICU. These patients may present with acidosis respiratory due to low lung compliance, metabolic due to acute kidney injury (AKI). Extra-corporeal CO2 removal techniques are increasingly used to stabilise the metabolic consequences of respiratory acidosis(1). The extracorporeal CO2 removal technique that we used in our patients consisted of a neonatal oxygenator placed in series to a hemofilter on a CRRT machine. Purpose of the study: This was a retrospective data collection of three ventilated critically ill patients with AKI who underwent CO2 removal alongwith renal replacement therapy by a modified technique. Method: We used a CVVHDF device (Prismaflex system, Gambro) with a standard setup and CRRT dose. The blood flow was maintained between ml/min. For CO2 removal, a microporous polypropylene neonatal oxygenator (Capiox Baby RX05, Terumo) with a maximum permissible blood flow of 1.5L/min was applied in series with CRRT hemofilter (M100, Gambro). Oxygen at a flow rate of 4l/min was passed through the oxygenator as the sweep gas for CO2 diffusion. The gas exchanger had an approximate surface area of 0.5m2. The retrospective data was collected on three ventilated critically ill patients with ARDS and AKI treated with above modalities. Arterial Carbon dioxide (PCO2), arterial oxygen (PO2), arterial sodium bicarbonate (HCO3) levels and arterial ph were recorded as per arterial blood gases (ABG). Other parameters like Plateau pressure (Pplat) and mean arterial pressure (MAP) was also recorded. Results: This combination therapy reduced average PCO2 by 28.9% in about 4 hours. The ph concomitantly increased by 0.12 (0.05 to 0.23). There was no appreciable change in PO2 levels (around 2%). The HCO3 levels changed as per the dose of CRRT. All patients tolerated the procedure without change in hemodynamics. The Pplat decreased by an average of 10% due to ultrafiltrate removal. Two patients could be weaned off to conventional ventilator strategies without hypercapnia. The third patient dies due to refractory shock. Conclusion: Extracorporeal CO2 removal alongwith CRRT may be a useful modality in patients with combined respiratory and metabolic acidosis with a positive impact on hemodynamic stability (2). S.No Patient 1 Patient 2 Patient 3 ph t=0 ph t=4 hrs ΔpH pco2 t=0 pco2 t=4 hrs Δ pco2 mmhg po2 t=0 po2 t=4 hrs Δ po2 mmhg

169 76 Experiences of blood purification using cytokine- adsorbing hemofilter (AN69ST) in pediatric population in Japan Masaaki Nunomura 1, Keiichi Motoyama 2, Hirota Saito 2, Fujiko Fukushima 2, Isho Izumi 2, Toshihiro Muraji 3 1 Department of Clinical Engineering, Ibaraki Children's Hospital, 2 Department of General Pediatrics, 3 Department of pediatric Surgery Background In Japan, blood purification with AN69ST (Sepxiris : Baxter) has been included in the insurance-covered therapeutic modalities for sepsis since July The AN69ST membrane is an AN69 membrane that is surface-treated with highly biocompatible polyethyleneimine. Therefore, AN69ST is now the first choice for severe sepsis and septic shock because of its remarkable ability of adsorbing cytokines. We report our experiences in using the AN69ST in infants and children from July 2014 to May Cases Four patients required blood purification using AN69ST in our hospital during this period. Their average body weight was 21.9 kg and average age, 6 years 11 months. Their primary diseases were Crohn's disease, acute pancreatitis, post-operative infection, and acute kidney disease. Equipment We used a console of TR-55X (Toray Medical, JP) with a blood circuit (U520-SZK-M, JUNKEN medical, JP) and hemofilter (Sepxiris60, Baxter, USA). Results No initial drop in blood pressure was encountered at the beginning of the blood purification. In the second case, whereby nafamostat mesylate (NM) was used alone, the circuit (V chamber) was coagulated 7 h after the start, and heparin was added for anticoagulation following circuit exchange. In the third and fourth cases, coagulation of the circuit was prevented for 24 h with an NM and heparin combination. The average blood purification time 168

170 was 162 h 20 min. The average NM dose was 0.48 mg/kg/h; average heparin dose, 2.9 IU/kg/h; average activated clotting time (ACT), 185 s on the A side and 209 s on the V-side; and increase ratio, 12.6%. The active prothrombin time (APTT) was pre-blood purification 45.7s and 57.8 s during blood purification; the increase ratio was 12.6%. In the case of hemofilters other than AN69ST used previously, the increase ratios were 45.7% and 210.2% for ACT and APTT, respectively, with an average NM dose of 0.48 mg/kg/h. Discussion The second patient required a circuit exchange because of circuit coagulation only 7 h after the start. Other institutions have reported that the V chamber was coagulated with anti-coagulation therapy using NM alone. Our experiences have shown trends of shortened ACT and APTT with the use of AN69ST, compared to the use of other hemofilters. Further investigation is warranted to determine whether or not AN69ST adsorbs NM. Conclusion NM alone does not provide adequate anti-coagulation when an AN69ST membrane is used. Heparin is recommended in combination with NM. 77 oxiris a novel continuous renal replacement therapy and cytokine & endotoxin adsorption in septic patients an Indian clinical experience Sachin Gupta 1, Deepak Govil 1, Shrikanth Srinivasan 1, Jagadeesh KN 1, Sweta J Patel 1, Anand Gupta 1, Deeksha S Tomar 1, Parmender Shokeen 1, Divya Pal 1, Amit Goel 1 1 Medanta The Medicity Introduction: Most of the recent studies on sepsis have revealed the presence of high concentrations of cytokines and endotoxins in blood. This triggers the cascade of multiorgan dysfunction. Blood purification by removal of these cytokines have shown to improve the clinical outcome in septic patients[1]. oxiris hemofilter (oxiris, Gambro Hospal, Sweden) is an AN69-based membrane, surface treated with a polyethyleneimine (PEI) and grafted with heparin[2] and has been implicated to have an efficient cytokine adsorbing capacity[3]. Purpose of the study: A retrospective data collection of 10 critically ill septic shock patients who underwent oxiris membrane based CRRT and its effect on hemodynamics and mortality. Method: We collected data on patients who underwent continuous venovenous hemodiafilteration (CVVHDF) by oxiris hemofilter. The blood flow was maintained between ml/min with a CRRT effluent dose of ml/kg. APACHE IV score, vasopressor requirement at T=0 (at start of therapy), at T=24 & T=48 (24 & 48 hrs after therapy) was recorded. Other variables like core temperature by rectal probe, mean arterial pressure (MAP), sepsis markers like procalcitonin (PCT) and percentage reduction in APACHE IV & SOFA score were recorded. Endotoxin assay was not measured in all patients and so was not recorded in the assessment. We also looked at the effect on mortality. Results: The average vasopressor dosage reduction was 32% (14-64%) within first 12 hours of initiation of oxiris therapy and the effect persisted during the duration of therapy. This resulted in increase of MAP by an average of 22% over the same period. Patients experienced reduction in core temperature during the entire duration of therapy. Procalcitonin did not show any major change (average reduction of 5%). APACHE IV and SOFA scores showed an average reduction during the next 48 hours (20% and 18% respectively). The average 169

171 life of oxiris membrane was 52 hours without the need of heparin anticoagulation. The endotoxin assay although not a part of the assessment did show a significant reduction (average 56%) in 5 patients in whom it was done before the start of therapy. Four patients died within next 5 days. Conclusion: oxiris membrane based CRRT does help in reduction in vasopressor dependency and improvement in hemodynamics and organ failure scores in critically ill patients. Mortality benefit could not be commented as we did not compare with a control cohort. Variables T = 0hrs T = 12hrs T = 24hrs T = 36hrs T = 48hrs Noradrenaline dose (ml/hr) MAP (mmhg) PCT (ng/ml) APACHE IV SOFA In vitro and preliminary in vivo evalutation of new CRRT machine: KIBOUTM Mauro Neri 1, Francesco Garzotto 2, Alessandra Brendolan 2, Federico Nalesso 2, Monica Zanella 2, Claudio Ronco 2 1 Department of mechatronics engineering, University of Padova, 2 Department of Nephrology, Dialysis and Transplantation and International Renal Research Institute of Vicenza Introduction: KibouTM (Asahi Kasei Medical Co., Tokyo, Japan) is a new multifunctional automatic machine for Continuous Renal Replacement Therapy (CRRT) (figure). Kibou can perform different CRRT therapies with the possibility to use only a single platform; in particular, modalities for both adults and pediatrics, counter-current and cocurrent configurations, the use of heparin or citrate-calcium anticoagulation therapies and plasma exchange can be delivered (figure). Methods: 170

172 Based on the traditional experience of International Renal Research Institute of Vicenza (IRRIV), in vitro and α test evaluation of Kibou and related disposables has been conducted. In particular, during in vitro phase all the possible modalities and treatments have been performed, even for 24 hours. The 12 in vivo treatments were performed: 3 SCUF, 3 CVVH, 3 CVVHD, 3 CVVHDF, all for adult patients. The treatment parameters have been set based on the clinical needing of the patients. Machine s usability and accuracy has been evaluated by the staff (clinicians, nurses and engineers) through scores table. The measurement of the accuracy of fluid balance system (gravimetric) has even been performed comparing the displayed values in the monitor of the machine and in the bed scales. CurefloTM ACF-130W filter has been used for the in vivo evaluation. Results: Based on score given by the staff, the machine hardware results compact and well organized (figure), with 3 well separated compartments (dialysate/replacement, blood and effluent) that facilitate the preparation phase. Auto-priming function allows short priming time. The interface is user friendly in all the modalities (SCUF, CVVH, CVVHD, CVVHDF, TPE, for adults and pediatrics). During the α test in vivo, the measured fluid balance error was always lower than 0.3%, in all the modalities. On the contrary CVVHDF pre-infusion and pre + post infusion are not performable. For pediatric treatment the continuity of the flow of peristaltic blood pump need to be maintained and improved. Conclusion: Kibou is a promising CRRT machine that can perform multiple continuous therapies with just one platform. In particular, we evaluated a highly accurate gravimetric fluid balance control system and a user friendly interface. Kibou is one of the first machines of the new frontier of CRRT devices: the fifth generation of CRRT machines. 171

173 79 Confirmation of Hemodialysis Central Venous Catheter Placement Using an Ultrasonographic Bubble Test Rogerio H Passos 1, Rosseane F Euzebio 1, Arianne R Velasquez 1, Felipe D Marques 1, José C Freitas 1, Marlon S Rossi 1, Michel P Abreu 1, Zilma S Barreto 1, Ana C Catttony 1, Paulo B Batista 1 1 Hospital Sao Rafael, Salvador,BA, BRAZIL Confirmation of Hemodialysis Central Venous Catheter Placement Using an Ultrasonographic Bubble Test Introdution The insertion of hemodialysis catheter is an integral part of the management of critically ill patients requiring continuous renal replacement therapy (CRRT). Doppler ultrasound imaging guidance for the insertion compared with anatomic landmarks, has benefits with respect to several clinical outcomes, and its routine use is strongly recommended. Traditionally, a postprocedural portable chest radiograph (CXR) is performed for catheter confirmation; however obtaining one can take up to several hours, delaying use of the catheter in critical patients requiring emergent dialysis initiation. The objective was to determine if ultrasound (US) can more rapidly confirm hemodialysis central venous catheter position in comparison to (CXR) Methods The study included a convenience sample of critically ill patients requiring CRRT with supradiaphragmatic hemodialysis catheters and a CXR for confirmation. Ultrasound was used for confirmation by visualizing microbubble artifact in the right atrium after injection of saline through the distal port. Blinded chart review was performed to assess CXR timing, catheter position and CVC complications. Student's t test was used to compare US time to CXR performance time and radiologist reading time. Results Thirty two patients were included in the final analysis. The visualization of turbulence or microbubbles within the RA within 2 seconds of the distal port flush confirmed adequate CVC placement with a 96% sensitivity and 93% specificity. Mean total US time was 3 minutes (95% confidence interval [CI], CI 2,2-3,9) 24 minutes (CI 16,8-39,4) for CXR performance, with a median diference of 21 minutes (CI 10,8-36,5, p<0,001. When comparing only US CVC confirmation time to CXR time, US was an average 24 minutes (CI 12,7 35,4, p<0,001) faster. Comparing total US time to radiologist CXR reading time, US was an average of 254 minutes faster (95% CI, to ; P < 00001). Conclusion The rapid appearance of prominent turbulence or microbubbles in the right atrium on chest ultrasound after CVC saline flush serves as a precise bedside screening test of optimal hemodialysis catheter position and was significantly faster than CXR in our population of critically ill patients requiring CRRT. 172

174 80 Development and validation of an Acute Kidney Injury prediction model in Intensive Care Unit Srinivasan Vairavan 1, Caitlyn Chiofolo 1, Nicolas Chbat 1, Kianoush Kashani 2 1 1Philips Research North America, Cambridge, MA, 2 Mayo Clinic, Rochester, MN Introduction: Acute Kidney Injury (AKI) is common and life-threatening medical condition seen in the critically ill population. Timely risk stratification of AKI high-risk patients facilitates prevention of its progression. Objective: Over the past few years, standardized diagnostic and staging criteria for AKI standardized AKI detection and its complications. However, these criteria do not have the ability to identify AKI high-risk patients, which could provide the clinicians with an opportunity to develop strategies for prevention, and treatment of AKI. The proposed AKI model is based on random forests approach and uses the signatures of AKI observed in vital signs, laboratory data, and acute conditions to predict AKI. Methods: This study is conducted in the ICUs of a tertiary care center. The training and validation cohort study subjects were Olmsted County, MN, residents admitted to all Mayo Clinic ICUs from July 1, 2010, through December 31, The Acute Kidney Injury Network criteria were used to define AKI. The prediction model was developed; its precision and reliability in the prediction of AKI were assessed in both training and validation cohorts. AKI adjudication was performed using a validated electronic surveillance tool which identified patients with AKI using AKIN criteria with a sensitivity of 88% and specificity of 96%. Results: Out of 7594 screened patients, a total of 6530 patients were included in the study: 5472 for training and 1958 for validation. Following training model in the first cohort, in the validation cohort, sensitivity, specificity and positive predictive value of the AKI prediction model were 93%, 66% and 41% positive predictive value (adjusted to 20% prevalence of AKI in ICU). In addition, the AKI prediction model detects 79% of AKI patients earlier than the reference standard and 33% of AKI patients 6 hours prior to the reference standard. Conclusion: Acute kidney injury can reliably and accurately be predicted electronically in ICU patients. 173

175 81 Better "dose" for CRRT? Deliver the prescribed Francesco Garzotto 1, Mauro Neri 1, Anna Lorenzin 1, Marta Zaccaria 1, Federico Nalesso 1, Alessandra Bredolan 1, Claudio Ronco 1 1 St Bortolo Hospital and IRRIV Introduction: historically, assuming the equilibration of low molecular weight solutes between the blood and dialysate, the dose of CRRT has been quantified with the effluent flow rates (the sum of net ultrafiltration, dialysate and replacement fluid) normalized to body weight. It may be reduced by pre-filter administration of replacement fluids or by membrane fouling caused by clotting and by protein concentration polarization. While the literature does not support the concept that more RRT is better, the same data suggest that there must be a lower limit below which mortality will increase. KDIGO AKI guidelines recommend delivering an effluent volume of ml/kg/h: prescribing a modestly higher dose of therapy in order to actually deliver the desired target doses; closely monitoring the delivered dose to assure that the targeted dose is actually achieved. 4th generation CRRT machines have becomes multi-organ support technologies that provides a wider range of extracorporeal treatment options. Aim of the present is to evaluate the Dose feature, both for prescription and treatment delivery, of the new Kibou (Asahi) CRRT machine. Methods: the kibou machine is equipped with a dose feature capable to calculate and display the instantaneous, the delivered and the target doses. Of the 24 treatment (12 with kibou and 12with others) (4+4 CVVH, 4+4 CVVHD and 4+4 CVVHDF) performed in our semi-intensive care unit, we calculate the number of flows settings changes and the effect on the dose. In addition we evaluate the prescribed vs delivered values. Results: Excluding blood flow changes we observe 35 (vs 22 others) flows variations when kibou machine were used. Post infusion (22 vs 8) was mainly increased while net UF varied only 8 (vs8) times. 75% (vs 60%) was in a favor of an higher dose. The delivery dose was the 96% of the prescribed for treatments done with Kibou and the 90% for the others. Nurses was comforted on the actual delivery dose displayed in the main page of the machine. Discussion: Even if a debate on the better dose for the patient is still open and actual, the delivery of the prescribed amount is mandatory in clinical practice. Our results are in favor with a dose feature integrated on the CRRT machine 174

176 RRT RESEARCH 82 Adverse Effects of Hypophosphatemia during Renal Replacement Therapy for Acute Kidney Injury Cynthia C Lim 1, Hui Zhuan Tan 2, Han Khim Tan 1, Manish Kaushik 1 1 Department of Renal Medicine, Singapore General Hospital, 2 Ministry of Health Holdings, Singapore Purpose: Hypophosphatemia in critically ill patients is common and may be exacerbated by dialysis. We aimed to identify risk factors and adverse outcomes associated with hypophosphatemia in intensive care unit (ICU) patients treated with dialysis for acute kidney injury (AKI). Methods: Secondary analysis of data from a single-center prospective cohort study of medical and surgical intensive care patients with acute kidney injury initiated on dialysis for AKI between 18th December 2010 and 3rd April Patients with premorbid serum creatinine 500 µmol/l, received dialysis prior to ICU admission, had incomplete dialysis data or died within 1 day of dialysis initiation were excluded. Demographic, comorbidity, laboratory and dialysis data were retrieved from patient case notes and electronic medical records. Outcomes assessed were hypophosphatemia (serum phosphate <0.94 mmol/l) during dialysis, ICU mortality and duration of mechanical ventilation and vasopressor support. Results: Median serum phosphate at initiation of acute dialysis was 1.63 mmol/l (IQR: 1.23, 2.43) in 96 patients. Twenty-five patients (26.0%) developed hypophosphatemia. On multi-variate logistic regression, serum phosphate at dialysis initiation [adjusted odds ratio (OR) 0.29 (95% CI (0.09, 0.91, p=0.03] was independently associated with hypophosphatemia during acute dialysis. Patients with hypophosphatemia during dialysis required longer ventilatory support [median 12 (IQR: 8, 17) days vs. 5 (3, 9) days, p<0.001] and vasopressor support [5 (4, 15) days vs. 2 (2, 6) days, p=0.003] compared to those without hypophosphatemia but there was no significant difference in ICU mortality [5 patients (20.0%) vs. 24 patients (33.8%), p=0.20]. Hypophosphatemia during dialysis was independently associated with prolonged mechanical ventilation ( 7 days) [adjusted OR 14.0 (1.37, ), p=0.03]. Conclusions: Mild hypophosphatemia during dialysis was associated with prolonged need for mechanical ventilation in critically ill patients with AKI. 175

177 83 Pharmacokinetics of Imipenem/Cilastatin in Critically Ill Burn Patients Undergoing High Volume Hemofiltation (HVHF) Joanna Q Hudson 1, Bradley A Boucher 1, S. Casey Laizure 1, Joseph M Swanson 1, G. Christopher Wood 1, David M Hill 2, Zheyi Hu 1, Angela Arnold-Ross 2, William L Hickerson 2 1 The University of Tennessee College of Pharmacy, Memphis, TN, 2 Regional One Health Firefighters Burn Center, Memphis, TN Purpose: High-volume hemofiltration (HVHF) is a modality used in septic burn patients for extracorporeal blood purification, volume removal, and removal of inflammatory mediators. Imipenem-cilastatin (I-C) is an antibiotic routinely used for treatment of severe sepsis in burn patients; however, dosing of I-C in patients undergoing HVHF is based on inference from previous studies assessing substantially different CRRT methods. To address this knowledge gap, we quantified the systemic and extracorporeal clearance (CL) of imipenem and cilastatin in burn patients undergoing HVHF. Methods: Adult critically ill burn patients receiving I-C for a documented infection and requiring HVHF were eligible for inclusion. I-C dosing and the prescribed HVHF dose were at the discretion of the medical team. Blood and effluent (E) samples for analysis of I-C concentrations were drawn in conjunction with a scheduled dose of I-C. Blood and E samples were collected at time 0 (blood only), 0.25, 0.5, 1, 2, 4, and 6 hours after the infusion and the total effluent was collected for calculation of I-C total CL (CLTotal), CL by HVHF (CL HVHF), half-life during HVHF, and the percentage of drug eliminated by HVHF. Drug concentrations were measured using liquid chromatography-mass spectrometry. Results: A total of 10 patients were enrolled (mean age 50±17 years, total body surface area burns 24±27%, 80% male). The I-C dose was 1 gram every 6 hours in 9 patients and 0.75 g every 8 hours in 1 patient; mean infusion time 87±10 minutes. The median I-C dose number prior to sampling was 4 (range 1-22). The indication for HVHF was AKI in 9 patients and sepsis in 1 patient. Characteristics of the HVHF procedures were: mean delivered dose 52 ± 14 ml/kg/hr (range 32-74), blood flow rate 318 ± 39 ml/min, effluent flow rate 4.3 ± 1.2 L/hr. The dialyzer used for HVHF was the Purema H polyethersulfone filter with all replacement fluid delivered pre-filter. The pharmacokinetic parameters of imipenem and cilastatin during HVHF are shown in the table. Conclusion: Removal of imipenem and cilastatin was substantial. More aggressive dosing of I-C in the burn population requiring this CRRT modality may be warranted depending on the infection and pathogen. Parameter Imipenem Cilastatin CLTotal (ml/min) 120 ± ± 20 CL HVHF (ml/min) 54 ± 8 33 ± 9 Half-life (hrs) 1.9 ± ± 0.4 % Removed by HVHF 48 ± 9 84 ±

178 84 Continuous renal replacement therapy in the NICU; ten years experience in a single center Mariko Sawada 1, Kayo Ogino 1, Tomohiro Hayashi 1, Masumi Saito 2, Akihito Takahashi 1, Shinichi Watabe 1, Kenji Waki 1, Yoshio Arakaki 1 1 Pediatrics, Kurashiki Central Hospital, Kurashiki, Okayama, JAPAN, 2 Clinical Engineering, Kurashiki Central Hospital, Kurashiki, Okayama, JAPAN Introduction: A Japanese clinical guideline of neonatal continuous renal replacement therapy (CRRT) was published in 2013; however, few neonatal intensive care units (NICUs) perform CRRT, and patient mortality remains high. Our objective was to study the clinical course of patients receiving CRRT in the NICU, and to analyze factors associated with mortality. Methods: We performed a retrospective observational study of all neonates who received CRRT at our NICU between 2005 and Patient characteristics, laboratory findings at initiation of CRRT, setting of CRRT, and 3-month mortality were reviewed retrospectively. Survivors and non-survivors were compared using univariate and multivariate analysis. Results: Twenty-seven patients received CRRT and had data available for analysis. Median patient age was 2 days (range, days), and median body weight was 2.9 kg (range, kg). Diaphragmatic hernia was the most common underlying disease, with associated shock due to persistent pulmonary hypertension of the newborn. No patients had renal or urological disease. The mean catheter size was 5.6Fr, and the insertion sites were femoral, jugular, and umbilical veins. The filter material was polysulfone and polyacryonitrile, and polyether sulfone. The mean membrane surface area was 0.29m2. The priming fluid of circuit was red blood cell in all patients. The anticoagulant was nafamostat mesilate. The mean blood flow was 12±6 ml/kg/min, and the mean CRRT dose was 208±140 ml/kg/h. Median treatment duration was 8 days (range, days). Overall survival was 51.9% within 3 months. To compare survivors and non-survivors, univariate and multivariate analysis indicated no risk factors for mortality. Non-survivors tended to have a lower PF ratio (93 versus 163), higher lactate (9.9 versus 4.4 mmol/l) and higher serum creatinine (1.77 versus 0.97 mg/dl), and higher %fluid overload (44.7 versus 11.4%). All survivors recovered to dialysis-independence at hospital discharge. All non-survivors died from their primary disease. Conclusion: In neonatal CRRT, the main cause of CRRT is not renal disease but circulatory insufficiency. Central and peripheral circulatory failure, and fluid overload might be risk factors for mortality in neonates. The mortality is high, but all survivors require neither dialysis nor management of chronic kidney disease. The survey of neonatal CRRT should be continued. 177

179 85 Early versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury (The ELAIN-Trial): a randomized clinical trial Alexander Zarbock 1, John A Kellum 2, Christoph Schmidt 1, Hugo Van Aken 1, Carola Wempe 1, Andreea Boanta 1, Joachim Gerss 3, Melanie Meersch 1 1 1Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Germany, 2 2Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, PA, USA, 3 Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany PURPOSE OF THE STUDY The optimal timing of initiation of renal replacement therapy (RRT) in patients with severe AKI but without life-threatening indication is still unknown. This study was performed to determine whether early initiation of RRT in critically ill patients with AKI reduces 90-day all cause mortality. METHODS In this single-center trial, we enrolled critically ill patients with AKI between August, 2013, and June, We enrolled 231 patients at a University hospital in Germany and randomized them to early or late initiation of RRT. All patients completed follow-up 90 days after randomization, and were analyzed according to the intention-to-treat principle. RRT was either initiated early (KDIGO stage 2) or late (stage 3). The primary endpoint was survival over the first 90-days after randomization. Secondary endpoints included 28- and 60-day survival, clinical evidence of organ dysfunction, recovery of renal function, requirement of RRT after day 90, duration of renal support, ICU and hospital length of stay and markers of inflammation. RESULTS Early initiation of RRT significantly reduced 90-day all-cause mortality (44 deaths (39.3%)) compared to late initiation of RRT (65 deaths (54.7%); HR, 0.66; 95% CI, ; P=0.03). More patients in the early group had renal recovered (60 (53.57%), versus 46 (38.66%); OR, 1.83; 95% CI, ; P=0.02). Furthermore, duration of RRT and length of hospital stay were significantly shorter in the early group compared to the late group, but there was no significant effect on requirement of RRT after day 90, organ dysfunction, and length of intensive care stay. Early initiation of RRT significantly attenuated the levels of proinflammatory mediators in the plasma of critically ill patients with AKI (interleukin 6 at day 1: early: vs late, ng/ml; Hodges-Lehmann estimation of location shift, 310.9; 95%CI, ; P <.001; interleukin 8 at day 1: early: 65.7 vs late, ng/ml; Hodges-Lehmann estimation of location shift, 105.9; 95% CI, ; P <.001). No safety signal was evident in either arm. CONCLUSION Among critically ill patients with AKI, early initiation of RRT significantly reduced 90-day allcause mortality. The observed reduction in mortality warrants further investigation. 178

180 86 Effect of the intensity of Continuous renal Replacement Therapy in Patients With cardiac surgery associated Acute Kidney Injury (CRITERIA STUDY) Huaban Liang 1, Li Song 1, Xinling Liang 1, Wei Dong 1, Zhilian Li 1, Ruizhao Li 1, Xia Fu 1, Wei Shi 1 1 Guangdong General Hospital and Guangdong Academy of Medical Sciences,Guangzhou,China Introduction. Acute kidney injury (AKI) is a major complication in patients with cardiac surgery and is an independent predictor of mortality. However, the optimal intensity of continuous renal replacement therapy(crrt) for such patients is still controversial. Methods. From 13 April 2011 to 9 August 2015, we randomly assigned 211 patients with Cardiac surgery-associated acute kidney injury (CSA-AKI) to continuous renal replacement therapy with different treatment dose (35ml / kg / h or 25ml/kg/h),The primary study outcome was death from any cause within 14, 28,90 and 365 days. Secondary outcomes were length of stay in the ICU and hospital and renal outcome of survivors at 14, 28,90 and 365 days after randomization. Results were analyzed by univariate and multivariate methods and by Kaplan Meier survival curves. Results. A total of 112 patients were given 35ml / kg / h and 99 were given 25ml / kg / h. There were no significant differences between the groups in number of deaths at 14, 28,90 or 365 days. There were also no differences between the groups in renal outcome of survivors at 14, 28,90 or 365 days. Conclusions. In patients with cardiac surgery associated acute kidney injury, the intensity of renal replacement therapy about 25 and 35 ml/kg/h had no effect on survival at 14,28, 90 or 365 days. 179

181 87 Relationship of Total Parenteral Nutrition Administration and Renal Replacement Therapy in the Intensive Care Unit Jose J Zaragoza 1, Missael V Espinoza-Villafuerte 1, Ivette Y Alférez-Jiménez 2, Jean P Vázquez-Mathieu 3, Turmalina I Salgado-Hernández 4, Ulises W Ceron-Diaz 1 1 Intensive Care Unit, Hospital Español. Mexico City, Mexico, 2 Intensive Care Unit, Hospital Angeles Lindavista. Mexico City, Mexico, 3 Intensive Care Unit, Hospital Angeles Lomas. Huixquilucan, Mexico, 4 Intensive Care Unit, Hospital Angeles Acoxpa. Mexico City, Mexico Purpose of the study: Adequate nutritional support is a mainstay of treatment of critically ill patients. In case of contraindications for enteral feeding, total parenteral nutrition (TPN) emerges as the next choice. Some adverse effects of TPN on kidney homeostasis have been reported. We ought to analyze the relationship between TPN and renal replacement therapy (RRT) in the Intensive Care Unit (ICU). Specifically, we hypothesized that TPN is a risk factor to receive RRT during ICU stay. Methods: This was a study in 4 hospitals in Mexico City. We used a prospectively collected administrative database conducted in all the ICUs. We included adult patients admitted between September 2009 and April 2015-Hospital A; January 2009 and December 2014-Hospital B; January 2013 and April 2015-Hospital C; January 2010 and March 2015-Hospital D. We excluded readmissions and transfers. A propensity score (PS) was created by a logistic regression model (LRM) with TPN or No-TPN as the dependent variable. The numeric value of this PS was included as covariable in a LRM with RRT as the outcome. The final model s stability was tested by Hosmer Lemeshow Goodness of fit test and bootstrapping. Lastly, a receiving operating curve (ROC) for predicting RRT by the final model was created. Results: In total, 4061 patients were admitted and 570 of them excluded. From the remaining 3491 patients, 250 (7.1%) received RRT. TPN was more frequently administered in those receiving RRT (16.3% vs 6%; p<0.001). The variables included in the PS creation were ICU days, enteral feeding, urgent surgical treatment, mechanical ventilation and hospital days. Significant variables related to RRT after LRM were male gender (OR 1.35, CI95% [ ]; p=0.030), organic failure (OR 5.54, CI95% [ ]; p<0.001), Saps3 predicted mortality (OR 1.01, CI95% [ ]; p<0.001) and TPN administration (OR 2.17, CI95% [ ]; p<0.001). Hosmer-Lemeshow Goodness of fit test resulted in a Chi-2 of 1.84 (p=0.98). The area under the ROC for predicting RRT was Conclusion: The administration of TPN was found to be related to RRT even after adjusting for various cofactors, including each patients propensity to receive TPN. Within the limitations of this study, results suggest that TPN might be consider a risk factor for RRT during ICU stay. Due to the high frequency which TPN is prescribed, and the still uncertain feasible adverse effects, a well design prospective trial is needed. Table and figure on following page 180

182 RRT OR p Value 95% CI 95% CI Bootstrap Bias Age <0.001 Male Gender Organic failure ϯ < Risk of failure ϯ Coronary disease MV SAPS < TPN < EF PS ϯ. vs Post-surgery care Abbreviations: RRT: Renal replacement therapy; OR: Odds ratio; TPN: Total parenteral nutrition; EF: Enteral feeding; MV: Mechanical ventilation; SAPS 3: Simplified Acute Physiology Score 3, CI: Confidence interval; PS: Propensity 181