We are submitting this application in response to RFA-DK-08-015 "Chronic Kidney Disease Biomarker Discovery and Validation Consortium." We propose to utilize the ongoing NIDDK-sponsored Chronic Renal Insufficiency Cohort (CRIC) as a Validation Site. We propose late-phase validation studies of established biomarkers of kidney injury and eady-phase validation studies of novel biomarkers identified by discovery activities within the Consortium. In both cases, we propose to use banked urine and plasma specimens from CRIC, a large NIDDK-sponsored longitudinal cohort study of over 3900 individuals with chronic kidney disease designed to identify new risk factors for chronic kidney disease progression. Specifically, we will determine levels of established sensitive biomarkers of kidney injury (urinary neutrophil- gelatinase-associated lipocalin, kidney injury molecule-1, liver fatty acid-binding protein, interleukin-18, cystatin C;and plasma plasminogen activator inhibitor-1) in CRIC. We hypothesize that higher levels of these biomarkers of kidney injury will be associated with more severe chronic kidney disease. We will also determine if absolute levels of kidney injury biomarkers or if changes in their levels correlate with subsequent loss of renal function (defined as progression to end stage renal disease or doubling of serum creatinine, a FDA-accepted endpoint for chronic kidney disease). We hypothesize that these markers of kidney injury will correlate with disease progression, and in fact will be independent predictors of future loss of renal function even after known clinical risk factors have been taken into consideration. Finally, we will use biosamples from CRIC to perform early phase validation studies for biomarkers discovered by members of the Chronic Kidney Disease Biomarker Consortium (including biomarkers discovered through our currently funded R21 CRIC ancillary proteomic study). Validating these biomarkers in an independent group of CRIC enrollees will serve as a paradigm for our approach to early validation studies in CRIC. If we are selected to be a member of the Chronic Kidney Disease Biomarker Consortium, CRIC will make available 2.5 mL of plasma and 5 mL of urine to the Consortium for biomarker validation efforts. The large and diverse CRIC cohort-with its detailed characterization of enrollees over time, excellent participant retention, and availability of carefully collected biospecimens-presents a unique and powerful platform to validate biomarkers of chronic kidney disease progression.
Chronic kidney disease is a major and growing health problem in the United States. Better markers to identify patients with chronic kidney disease who are at high risk of disease complications (such as progression of disease) are desperately needed. We propose here to test the predictive value of biomarkers for chronic kidney disease progression in patient samples from the ongoing NIDDK-sponsored Chronic Renal Insufficiency Cohort (CRIC), a longitudinal study with more than 3900 participants.
|Foster, Meredith C; Coresh, Josef; Hsu, Chi-Yuan et al. (2016) Serum Î²-Trace Protein and Î²2-Microglobulin as Predictors of ESRD, Mortality, and Cardiovascular Disease in Adults With CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 68:68-76|
|Waikar, Sushrut S; Sabbisetti, Venkata; Ã„rnlÃ¶v, Johan et al. (2016) Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies. Nephrol Dial Transplant 31:1460-70|
|Bansal, Nisha; Carpenter, Myra A; Weiner, Daniel E et al. (2016) Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial. J Am Soc Nephrol 27:2109-21|
|Fufaa, Gudeta D; Weil, E Jennifer; Nelson, Robert G et al. (2015) Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus. Nephrol Dial Transplant 30:599-606|
|Fufaa, Gudeta D; Weil, E Jennifer; Nelson, Robert G et al. (2015) Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus. Diabetologia 58:188-98|
|Hsu, Chi-Yuan; Ballard, Shawn; Batlle, Daniel et al. (2015) Cross-Disciplinary Biomarkers Research: Lessons Learned by the CKD Biomarkers Consortium. Clin J Am Soc Nephrol 10:894-902|
|Liu, Kathleen D; Yang, Wei; Go, Alan S et al. (2015) Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 65:267-74|
|Foster, Meredith C; Coresh, Josef; Bonventre, Joseph V et al. (2015) Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study. Clin J Am Soc Nephrol 10:1956-63|
|Foster, Meredith C; Inker, Lesley A; Hsu, Chi-Yuan et al. (2015) Filtration markers as predictors of ESRD and mortality in Southwestern American Indians with type 2 diabetes. Am J Kidney Dis 66:75-83|
|Rebholz, Casey M; Grams, Morgan E; Coresh, Josef et al. (2015) Serum fibroblast growth factor-23 is associated with incident kidney disease. J Am Soc Nephrol 26:192-200|
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