Urinary Biomarkers of Chronic Kidney Disease Pathology and Progression

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DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is common, harmful, and treatable. One of the major obstacles to the care of individuals with and at risk for CKD is the lack of sensitive and specific biomarkers to measure disease onset, progression, prognosis, and response to treatment. Our proposal to join the CKD Biomarker Consortium as a validation site for urinary biomarkers of CKD draws from our experience with discovery and validation of novel tubular injury biomarkers in preclinical and clinical settings as well as interactions with regulatory agencies such as the Food and Drug Administration. We propose bringing to the CKD Biomarker Consortium four cohorts with available urine samples to validate urinary biomarkers: 1) A kidney biopsy biospecimens bank from Brigham and Women's Hospital (N = 121 native and 78 allograft to date; enrollment 1 to 3 per week). 2) A kidney biopsy biospecimens bank of IgA nephropathy, lupus nephritis, renal vasculitis, and Chinese herbal nephropathy from our established collaboration with Peking University First Hospital (PUFH) in Beijing, China (N = 430; enrollment 7 per month); 3) An epidemiological study on endemic (Balkan) nephropathy from the University of Zagreb School of Medicine (N = 1074; additional 500 to 700 in 2010); 4) An observational cohort of lupus patients seen at the Brigham and Woman's Hospital Lupus Center (N=40 to date; enrollment expected to be ~300 withing 24 months). Our access to large and diverse cohorts of individuals with and at risk for CKD will provide ample statistical power to investigate the clinical utility of the following urinary biomarkers: kidney injury molecule-1 (KIM-1); N-acetyl-beta-D-glucosaminidase (NAG); neturophil gelatinase-associated lipocalin (NGAL); urinary L-type fatty acid binding protein (L-FABP); interleukin-18 (1L-18); urinary cystatin C; albumin; hepatocyte growth facmr (HGF); interferon-inducible protein (IP-10); and connective tissue growth factor (CTGF). We hypothesize that urinary biomarkers noninvasively predict histopathological findings on kidney biopsy, which are in turn predictive of CKD progression; and that urinary biornarkers are superior to conventional markers (serum creatinine and albuminuria) as predictors of CKD progression. PUBLIC HEALTH RELEVANCE: Chronic kidney disease afflicts more than 11% of the United States population and is one of the most potent predictors of cardiovascular disease and all-cause mortality. The identification of clinically useful CKD biomarkers will improve the care of individuals with and at risk for CKD.