Accepted Manuscript. Looking to Prevent Acute Kidney Injury After Cardiac Surgery? Just Check the Urine.

Transcription

1 Accepted Manuscript Looking to Prevent Acute Kidney Injury After Cardiac Surgery? Just Check the Urine. Daniel T. Engelman, MD, FACS, Michael J. Germain, MD PII: S (18) DOI: /j.jtcvs Reference: YMTC To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 24 August 2018 Accepted Date: 27 August 2018 Please cite this article as: Engelman DT, Germain MJ, Looking to Prevent Acute Kidney Injury After Cardiac Surgery? Just Check the Urine., The Journal of Thoracic and Cardiovascular Surgery (2018), doi: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 Looking to Prevent Acute Kidney Injury After Cardiac Surgery? Just Check the Urine. Daniel T Engelman MD, FACS Department of Surgery Baystate Medical Center, Springfield, MA University of Massachusetts Medical School Baystate, Springfield, MA Conflicts of interest: Co-Founder HealthChain Solutions, Consultant for Astute Medical, Medical Advisory Board for Pavillion Medical, Consultant for Zimmer-Biomet Michael J. Germain MD Renal and Transplant Associates of New England, Hampden, MA, United States. Conflicts of interest: Speaker for Astute Medical Corresponding Author: Daniel Engelman MD FACS 759 Chestnut Street, Springfield, MA Daniel.Engelman@baystatehealth.org

3 Looking to Prevent Acute Kidney Injury After Cardiac Surgery? Just Check the Urine. Daniel T. Engelman MD, FACS and Michael J. Germain MD In 1776 Dr. Matthew Dobson confirmed that the sweet taste of a diabetic patient s urine comes from an excess of glucose. 1 Today we have an arsenal of more sophisticated urinary biomarker tests, one of which has shown promise to predict the occurrence of acute kidney injury (AKI). AKI can be considered the "Achilles' heel" of cardiac surgical procedures. Frequently unpredictable, its occurrence, though often reversible, predicts an increased long-term mortality rate independent of other risk factors even when kidney function has recovered. 2 Historically, the ability of clinicians to reliably diagnose patients at risk for developing AKI has been limited. In this novel study by Cummings and colleagues 3, they measured a novel urinary biomarker, Nephrocheck (NC) which quantitatively measures two urinary biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP-7), markers of cell cycle arrest, and combines them into a single AKIRisk Score. Using NC, patients who would subsequently develop stage II or III AKI could be identified immediately following the completion of cardiopulmonary bypass. NC afforded even greater predictability 6 hours after ICU admission. Each 10- fold increase in intraoperative NC was associated with a 290% increased risk of stage 2-3 AKI and the 6- hour postoperative NC test was associated with a 650% increased risk. These elevations occurred prior to any elevation in serum creatinine, or documented kidney injury. The NC urinary biomarker appears to be more of a kidney "stress" indicator, though recent evidence has suggested that patients with NC elevations have some evidence of long-term decrease in renal functional reserve (the normal increase in GFR after a protein load). 4 Just as importantly, this test had a 100% negative predictive value, as none of those patients with a negative NC went on to develop significant AKI postoperatively. This study demonstrated that there is a bimodal elevation of NC associated with postop moderatesevere AKI. The greater utility appeared to be at 6-24 hours after ICU admission, though this limits the ability of care providers to intervene on those patients at greatest risk at the earliest possible time. The NC level remained significantly elevated through postoperative day #1 in patients with moderate to severe AKI, returning to baseline at postop day #2. Of significance, the NC level upon ICU admission was not predictive for the subsequent development of AKI. The authors have multiple explanations for the normalization of the NC value upon ICU admission in these at-risk patients, though none are conclusive. They suggest performing the test both in the operating room at the completion of the procedure (which was not done in their study) and again 4-6 hours after admission, to capture all renal stress events. This is only a single center experience, which included both on-pump and off-pump patients, having diverse procedures in an elective setting. It does not identify the specific intraoperative stressors that lead to a bump in NC. In addition, there was no evidence in this trial that early identification of at-risk patients would allow modifiable interventions to reduce the development of AKI. Nonetheless, others have demonstrated that the incidence of postcardiac surgical AKI can be reduced by 30% with directed implementation of care bundles based on the Kidney Disease Improving Global Outcomes AKI guideline in NC biomarker-positive patients. 5 Utilizing the NC test the morning after cardiac surgery, we have

4 demonstrated that interventions can eliminate stage 3 AKI from developing in all patients over a 1-year timeframe following isolated CABG procedures. [Implementation of a Multidisciplinary Acute Kidney Response Team Triggered by Urinary Biomarkers After Cardiac Surgery. Presented at the Society of Thoracic Surgeons Multidisciplinary Cardiovascular and Thoracic Critical Care Conference, Oct. 5, 2018, Washington, DC.] This study moves us forward toward individualization and optimization of patient care in this patient population. Earlier interventions taken during the cardiac surgical procedure, in addition to postoperative interventions, may further reduce the incidence of AKI in this high-risk population. 1 Dobson M. (1776)."Nature of the urine in diabetes". Medical Observations and Inquiries. 5: Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation. 2009;119: Cummings JJ, Shaw AD, Shi J, et al. Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest. J Thorac Cardiovasc Surg. In press. 4 Husain-Syed F, Ferrari F, Sharma A., et. al. Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery. Nephrology Dialysis Transplantation, July Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. Prevention of cardiac surgeryassociated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43:

5