Acute kidney injury (AKI) is common after cardiac surgery and impacts short and long-term mortality. The parent grant, RO1 (HL-085757), focused on developing novel tools for assessment of structural kidney damage and comparing new tests to the traditional measurement of serum creatinine, which is a measure of kidney filtration. We created the Translational Research Investigating Biomarker Endpoints (TRIBE) consortium and fulfilled the goals of all of the specific aims of the grant and reported results on several novel urine and plasma biomarkers of kidney injury, such as urine IL-18, urine and plasma NGAL, urine albumin, plasma BNP, and plasma cystatin C. We prospectively enrolled over 2000 adults and children undergoing cardiac surgery at 9 centers and developed a robust sample biorepository linked to clinical variables. In this competitive renewal, we will enrich our cohort y gathering information on long-term outcomes in adult and pediatric patients through continued phone calls, in-person visits, and linkages of the TRIBE cohort to national administrative databases. We will also perform measures of three promising urine biomarkers (KIM- 1, L-FABP and urine cystatin C) and two plasma biomarkers (CK-MB, high sensitivity troponin-T) on the samples stored in our biorepository. With a total of 11 measured biomarkers (from the parent and renewal grants), we will create multi-marker panels for predicting AKI and other outcomes using emerging and innovative statistical methods. We hypothesize that the pre-operative and post-operative biomarkers will not only predict AKI, but also will predict longer-term complications years later, such as chronic kidney disease, end-stage renal disease, and death. Additionally, we hypothesize those patients with high biomarker levels, but no evidence of clinical AKI (subclinical AKI);will also have poor long-term outcomes. The availability of reliabl clinical models for these short and long-term outcomes will assist with informed decision making, adequate planning for surgeons, post-discharge management, and inform future clinical trials. Our primary research aims are:
Aim 1 : To ascertain long-term outcomes associated with AKI after cardiac surgery in adults and children.
Aim 2 : To construct a multi-marker biomarker panel to improve risk prediction of outcomes in adults and children.

Public Health Relevance

Acute Kidney Injury (AKI), is common complication in adults and children undergoing cardiac surgery. AKI has enormous impact on morbidity, mortality and resource utilization. In this proposal, we evaluate novel urinary biomarkers and their relationship to mortality, decline in kidney function and clinical outcomes. We plan to develop a novel panel of biomarkers to predict AKI and its sequelae;a potential method for the early detection of kidney injury and ultimately the development of therapies to reduce the burden of AKI.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-DKUS-A (05))
Program Officer
Miller, Marissa A
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Belley-Côté, Emilie P; Parikh, Chirag R; Shortt, Colleen R et al. (2016) Association of cardiac biomarkers with acute kidney injury after cardiac surgery: A multicenter cohort study. J Thorac Cardiovasc Surg 152:245-251.e4
Coca, Steven G; Nadkarni, Girish N; Garg, Amit X et al. (2016) First Post-Operative Urinary Kidney Injury Biomarkers and Association with the Duration of AKI in the TRIBE-AKI Cohort. PLoS One 11:e0161098
Parikh, Chirag R; Moledina, Dennis G; Coca, Steven G et al. (2016) Application of new acute kidney injury biomarkers in human randomized controlled trials. Kidney Int 89:1372-9
Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather et al. (2016) Methodological issues in current practice may lead to bias in the development of biomarker combinations for predicting acute kidney injury. Kidney Int 89:429-38
Schaub, Jennifer A; Parikh, Chirag R; TRIBE-AKI Consortium (2016) The Authors Reply. Kidney Int 89:1162-3
Kerr, Kathleen F; Brown, Marshall D; Zhu, Kehao et al. (2016) Assessing the Clinical Impact of Risk Prediction Models With Decision Curves: Guidance for Correct Interpretation and Appropriate Use. J Clin Oncol 34:2534-40
Park, Meyeon; Shlipak, Michael G; Thiessen-Philbrook, Heather et al. (2016) Association of Peak Changes in Plasma Cystatin C and Creatinine With Death After Cardiac Operations. Ann Thorac Surg 101:1395-401
Koyner, Jay L; Coca, Steven G; Thiessen-Philbrook, Heather et al. (2015) Urine Biomarkers and Perioperative Acute Kidney Injury: The Impact of Preoperative Estimated GFR. Am J Kidney Dis 66:1006-14
Bucholz, Emily M; Whitlock, Richard P; Zappitelli, Michael et al. (2015) Cardiac biomarkers and acute kidney injury after cardiac surgery. Pediatrics 135:e945-56
Zappitelli, Michael; Greenberg, Jason H; Coca, Steven G et al. (2015) Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery. JAMA Pediatr 169:583-91

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