Conflicts of Interest

Nephrotoxic Injury Negated by Just in time Action (NINJA) Stuart L. Goldstein, MD, FAAP, FNKF Director, Center for Acute Care Nephrology Nephrology & Hypertension The Heart Institute Conflicts of Interest Baxter Healthcare Speaker s Bureau Grant support Consultant Consultant AM Pharma Akebia Astute Medical Bellco BPL Otuska

High Level Rationale for NINJA One of the most common causes of AKI in non-critically ill hospitalized children A portion of NTMx-AKI goes unnoticed due to lack of systematic kidney function surveillance in exposed children Multiple studies show SCr measured at least every four days only 50% of the time in children receiving multiple NTMx NTMx-AKI may be a potentially modifiable adverse safety event if At-risk patients are identified Systematic SCr monitoring is instituted reliably in at-risk patients AKI is avoided and/or mitigated by reducing unnecessary NTMx exposure Motivation or Why did I get interested in NTMx-AKI? Frequent consults for patients receiving multiple NTMx with AKI Tired of writing AKI secondary to NTMx, we will follow with you, in the chart Early NTMx-AKI epidemiological research to get an accurate AKI rate was difficult SCr surveillance inconsistent and differed between services Started as an economic exercise NINJA Vision Statement Children should only get the nephrotoxic medications they need for the duration they need them

Patients receiving IV AG > 5 days Primary renal diagnoses excluded One year of study 557 children 95% > 3 months of age AKI occurred in SCr measured at least q4 days only 50% of the time 350 non-critically ill children with AKI by prifle 350 matched children without AKI 38 potential NTMx Compared NTMx exposure rate between AKI vs. non- AKI patients 86% exposed to at least 1 NTMx Patients with AKI had 1.7 OR for exposure to a NTMx PPV for AKI doubles for patient with 3+ NTMx Objectives of NINJA Develop and EHR-based AKI screening intervention to assess changes in AKI prevalence, or duration (intensity) RELIABLY QUANTIFY the rate of High NTMx exposure and NTMx-AKI in the non-critical care population.

High NTMx-exposure Criteria Patient receiving 3 or more nephrotoxic medications (NTMx) concomitantly* or On an aminoglycoside for 3 or more days *IV radiology contrast, amphotericin, or cidofovir in previous week is counted for the week following administration Nephrotoxic Medication List AKI Definition

Outcome Measures The Process Pharmaci sts create/ receive daily reports, verify & validate Provide SCr screening suggestio ns if necessary Data Analyst compiles registry from Pharmaci st reports and generate metrics, run charts Share with AKI team, leadershi p, other stakehold ers AKI Surveillance Algorithm

AKI Surveillance Algorithm Meets High NTMx Exposure Criteria AKI Surveillance Algorithm Injury surveillance loop AKI Surveillance Algorithm Exposure surveillance loop

AKI Surveillance Algorithm End Surveillance

Inclusion Flowchart 99% compliance with daily SCr monitoring in all high NTMx-exposed patients Data span June 2, 2011 June 4, 2012 EHR Trigger reports improve detection of NTMx exposure in Year 1

Initial AKI prevalence rates 10-fold higher than CAUTI rates and 3-fold higher than CLBSI rates at CCHMC AKI intensity decreases in Year 1 of the project by 42% Associated with 908 AKI days avoided in one year

Goldstein SL et al: submitted Goldstein SL et al: submitted Goldstein SL et al: submitted

Goldstein SL et al: submitted Adverse Events Avoided Measure 2011 * 2012 2013 2014 2015 * Aggregate Annualized Non-Critically Ill Patient Days (Actual Count) 97,065 (26,133) 91,363 90,627 99,076 109,968 (27,492) 334,691 Census Days Annualized Number Of Patient Exposures (Actual Count) 1,129 (304) 969 837 960 692 (173) 3,243 Patient Exposures Annualized Number Of Patients With AKI (Actual Count) 271 (73) 168 141 159 116 (29) 575 Patients With AKI Patient Exposures Avoided N/A 108 200 219 106 633 Avoided Exposures Patients With AKI Avoided N/A 105 113 134 46 398 Avoided AKI Events * Data presented for partial year. Annualized values represent if data were extrapolated to full time period. Study period in 2011 (Sept Dec), in 2015 (January March). All aggregate data are actual count. Goldstein SL et al: submitted Potential Adverse Consequence?

First 100 patients with NTMx-AKI assessed at > 6 months after AKI episode Review of electronic health record Nephrology Clinic visit (y/n) Serum creatinine Urine for protein and creatinine Cystatin C GFR estimation from serum creatinine and/or CysC egfr (ml/min/1.73m 2 ) <90 0/100 Before AKI Hospital DC 6 months post-aki 22/92 (5<60) 18/77 (2< 60) 90-150 100/100 70/92 50/77 >150 0/100 0/92 9/77 Cystatin C egfr (ml/ min/1.73m 2 ) N/A N/A 80+23 Urine protein/creat >0.2 0/15 N/A 27/34

Dissemination of NINJA Disseminate NINJA implementation at nine pediatric hospitals Measure the impact of NINJA on NTMx-AKI in participating hospitals Assess the association between context measures, including network participation, and reduction in NTMx-AKI by individual hospitals across the network 12 The Rate of Patients with Nephrotoxic Medication (NTMx) Exposure per 1000 Non-ICU Patient Days 10.9195 Exposure Rate 8.7672 9 8.131 7.9329 7.2936 7.405 6.9353 7.0446 7.2456 7.3603 7.2202 6.8725 6.7423 6.44326.4432 5.8296 6 5.9417 5.8617 6.0267 5.6648 8.2807 8.3963 7.6947 7.29346.9806 7.2169 7.55887.5423 6.3905 6.5986 3 0 10/1-10/14, 2014 10/15-10/31, 2014 11/1-11/14, 2014 11/15-11/30, 2014 12/1-12/14, 2014 12/15-12/31, 2014 1/1-1/14, 2015 1/15-1/31, 2015 2/1-2/14, 2015 2/15-2/28, 2015 3/1-3/14, 2015 3/15-3/28, 2015 3/29-4/11, 2015 4/12-4/25, 2015 4/26-5/ 9, 2015 5/10-5/23, 2015 5/24-6/ 6, 2015 6/6-6/20, 2015 6/21-7/4, 2015 7/ 5-7/l18, 2015 7/19-8/1, 2015 8/2-8/15, 2015 8/16-8/29, 2015 8/30-9/12, 2015 9/13-9/26, 2015 9/2-10/10/2015 11/8-11/21, 2015 10/11-10/24/2015 10/25-11/7, 2015 11/22-12/5, 2015 High NTMx Exposure Rate Median High NTMx Exposure Rate Goal 3 Rate of Nephrotoxic Medication (NTMx) associated Acute Kidney Injury (AKI) per 1000 Non-ICU Patient Days Maturity Detection System AKI Rate 2.4138 2.4377 2.273 2.25 1.94 1.9113 1.758 1.7842 1.7984 1.6565 1.586 1.5597 1.5 1.2914 1.3382 1.3075 1.2804 1.2081.2081 1.1896 1.1497 0.8842 0.9908 0.9997 0.8806 0.8792 0.899 0.9627 0.78480.7848 0.7736 0.75 0 10/1-10/14, 2014 10/15-10/31, 2014 11/1-11/14, 2014 11/15-11/30, 2014 12/1-12/14, 2014 12/15-12/31, 2014 1/1-1/14, 2015 1/15-1/31, 2015 2/1-2/14, 2015 2/15-2/28, 2015 3/1-3/14, 2015 3/15-3/28, 2015 3/29-4/11, 2015 4/12-4/25, 2015 4/26-5/ 9, 2015 5/10-5/23, 2015 5/24-6/ 6, 2015 6/6-6/20, 2015 6/21-7/4, 2015 7/ 5-7/l18, 2015 7/19-8/1, 2015 8/2-8/15, 2015 8/16-8/29, 2015 8/30-9/12, 2015 9/13-9/26, 2015 9/2-10/10, 2015 11/8-11/21, 2015 10/11-10/24, 2015 10/25-11/7, 2015 0.1245 11/22-12/5, 2015 AKI Rate Median AKI Rate Goal

40.0 Percent of patients with Nephrotoxic Medication (NTMx) Exposure who develop Acute Kidney Injury (AKI) 34.9206 Percent with AKI 30.0 20.0 10.0 12.963 13.4615 12.1212 10.6061 14.2857 12.5 23.0769 23.0769 23.0769 15 22.2222 17.6471 18.1818 16.4179 13.5593 25.9259 13.3333 21.6216 14.4928 22.1053 15.7895 30.3571 24.3243 22.7273 21.25 17.7419 23.4375 18.5714 % 1.8868 0.0 10/1-10/14, 2014 10/15-10/31, 2014 11/1-11/14, 2014 11/15-11/30, 2014 12/1-12/14, 2014 12/15-12/31, 2014 1/1-1/14, 2015 1/15-1/31, 2015 2/1-2/14, 2015 2/15-2/28, 2015 3/1-3/14, 2015 3/15-3/28, 2015 3/29-4/11, 2015 4/12-4/25, 2015 4/26-5/ 9, 2015 5/10-5/23, 2015 5/24-6/ 6, 2015 6/6-6/20, 2015 6/21-7/4, 2015 7/ 5-7/l18, 2015 7/19-8/1, 2015 8/2-8/15, 2015 8/16-8/29, 2015 8/30-9/12, 2015 9/13-9/26, 2015 9/2-10/10, 2015 10/11-10/24, 2015 10/25-11/7, 2015 11/8-11/21, 2015 11/22-12/5, 2015 Monthly Percent of Patients with AKI Median Percent of Patients with AKI Goal 30 Acute Kidney Injury (AKI) Days per 100 High NTMx Exposure Days 26.1538 24.8538 22.5 21.6617 20 19.0476 20.5314 16.6667 17.0507 16.3755 AKI Days 15 7.5 13.212.9921 7.4627 7.8717 10.5882 10.7477 11.9481 10.0304 8.8652 13.8767 14.1892 10.6287 8.8542 8.9005 7.5734 7.9044 5.5743 4.2959 11.658 11.2426 0 10/1-10/14, 2014 10/15-10/31, 2014 11/1-11/14, 2014 11/15-11/30, 2014 12/1-12/14, 2014 12/15-12/31, 2014 1/1-1/14, 2015 1/15-1/31, 2015 2/1-2/14, 2015 2/15-2/28, 2015 3/1-3/14, 2015 3/15-3/28, 2015 3/29-4/11, 2015 4/12-4/25, 2015 4/26-5/ 9, 2015 5/10-5/23, 2015 5/24-6/ 6, 2015 6/6-6/20, 2015 6/21-7/4, 2015 7/ 5-7/l18, 2015 7/19-8/1, 2015 8/2-8/15, 2015 8/16-8/29, 2015 8/30-9/12, 2015 9/13-9/26, 2015 9/2-10/10, 2015 11/8-11/21, 2015 10/11-10/24, 2015 10/25-11/7, 2015 0.3247 11/22-12/5, 2015 AKI Days Median AKI Days Goal Vision for NINJA Develop reliable AKI detection and mitigation across the collaborative Once the clinical NINJA engine is in place, this reliable NTMx-AKI phenotype will allow for: Disease specific epidemiology and AKI reduction strategies Development of translational research initiatives Pharmacogenomics AKI biomarker validation Personalized AKI detection and reduction strategies

Acknowledgements Eric Kirkendall, MD, MBI Stephen Muething, MD Theresa Mottes, RN, BSN Jason Olivea Cynthia Barclay, PharmD