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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK082185-03
Application #
7912963
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Kimmel, Paul
Project Start
2008-09-01
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
3
Fiscal Year
2010
Total Cost
$489,853
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Coca, Steven G (2018) ""Scanning"" into the Future: The Promise of SOMAScan Technology for Kidney Disease. Kidney Int Rep 3:1020-1022
Greenberg, Jason H; Kakajiwala, Aadil; Parikh, Chirag R et al. (2018) Emerging biomarkers of chronic kidney disease in children. Pediatr Nephrol 33:925-933
Greenberg, Jason H; Zappitelli, Michael; Jia, Yaqi et al. (2018) Biomarkers of AKI Progression after Pediatric Cardiac Surgery. J Am Soc Nephrol 29:1549-1556
Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather et al. (2018) Development of biomarker combinations for postoperative acute kidney injury via Bayesian model selection in a multicenter cohort study. Biomark Res 6:3
Wilson, F Perry; Parikh, Chirag R (2018) Translational Methods in Nephrology: Individual Treatment Effect Modeling. J Am Soc Nephrol 29:2615-2618
Greenberg, Jason H; Devarajan, Prasad; Thiessen-Philbrook, Heather R et al. (2018) Kidney injury biomarkers 5 years after AKI due to pediatric cardiac surgery. Pediatr Nephrol 33:1069-1077
Moledina, Dennis G; Hall, Isaac E; Thiessen-Philbrook, Heather et al. (2017) Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury. Am J Kidney Dis 70:807-816
Nadkarni, Girish N; Coca, Steven G; Meisner, Allison et al. (2017) Urinalysis findings and urinary kidney injury biomarker concentrations. BMC Nephrol 18:218
Greenberg, Jason H; Parikh, Chirag R (2017) Biomarkers for Diagnosis and Prognosis of AKI in Children: One Size Does Not Fit All. Clin J Am Soc Nephrol 12:1551-1557
de Fontnouvelle, Christina A; Greenberg, Jason H; Thiessen-Philbrook, Heather R et al. (2017) Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery. Ann Thorac Surg 104:2072-2079

Showing the most recent 10 out of 53 publications