The short-term deleterious effects of acute kidney injury (AKI) on morbidity and mortality are well-known from several epidemiological studies. However, the long-term sequelae of AKI have not been thoroughly explored. Although AKI has been widely considered a reversible disease, studies now suggest that AKI may cause or contribute to progression of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is also growing evidence that AKI has long-term effects on overall survival;even many years after recovery from an episode AKI, patients suffer from premature death. We, the Translational Research Investigating Biomarkers in AKI Network (TRIBE-AKI Network), propose to conduct a landmark prospective cohort study of 1,800 patients (adult and pediatric) undergoing cardiac surgery at seven academic centers. We will study the entire cohort for the development of ESRD and death over time. Additionally, we will intensively follow 300 AKI patients and 300 randomly selected non-AKI patients for a mean of 4 years (range 3 to 5 years) in order to understand the long-term effects of AKI on the progression of kidney disease (change in glomerular filtration rate as determined by change in serum creatinine and change in serum cystatin C). The proposed study will be an extension of an NIH-funded study (R01-HL08676, funding from 04/07- 3/12) that is validating the role of newer biomarkers of AKI in the setting of cardiac surgery.
The aims of this longitudinal study are: 1) to determine whether AKI is associated with accelerated decline in kidney function;2) to determine the composite risk of ESRD and all-cause mortality in patients after AKI as defined by creatinine-based definitions of AKI;and 3) to evaluate the prognostic value of elevations in serum cystatin C and urinary biomarker concentrations (IL-18, NGAL) for the future development of ESRD and for mortality. The overall goals of this project are to determine the long-term associations between AKI and CKD and long-term mortality. We hypothesize that AKI will increase progression to CKD and contribute to premature death, and that the new biomarkers of AKI will be predictive of these outcomes. Public Health Relevance: The overall goals of this project are to determine the long-term associations between AKI and CKD and long-term mortality.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Kimmel, Paul
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
Zip Code
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
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
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
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
Zhang, William R; Garg, Amit X; Coca, Steven G et al. (2015) Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery. J Am Soc Nephrol 26:3123-32
Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D et al. (2015) National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury. J Am Med Inform Assoc 22:1054-71

Showing the most recent 10 out of 39 publications