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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK085660-02
Application #
7938644
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O1))
Program Officer
Kimmel, Paul
Project Start
2009-09-30
Project End
2014-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$178,000
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Srivastava, Anand; Kaze, Arnaud D; McMullan, Ciaran J et al. (2018) Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD. Am J Kidney Dis 71:362-370
Srivastava, Anand; Palsson, Ragnar; Kaze, Arnaud D et al. (2018) The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study. J Am Soc Nephrol 29:2213-2224
Emerson, Sarah C; Waikar, Sushrut S; Fuentes, Claudio et al. (2018) Biomarker validation with an imperfect reference: Issues and bounds. Stat Methods Med Res 27:2933-2945
Leaf, David E; Siew, Edward D; Eisenga, Michele F et al. (2018) Fibroblast Growth Factor 23 Associates with Death in Critically Ill Patients. Clin J Am Soc Nephrol 13:531-541
Inker, Lesley A; Coresh, Josef; Sang, Yingying et al. (2017) Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis. Clin J Am Soc Nephrol 12:69-78
Wheelock, Kevin M; Cai, Jian; Looker, Helen C et al. (2017) Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus. PLoS One 12:e0180964
Leaf, David E; Waikar, Sushrut S (2017) End Points for Clinical Trials in Acute Kidney Injury. Am J Kidney Dis 69:108-116
Birmingham, Daniel J; Merchant, Michael; Waikar, Sushrut S et al. (2017) Biomarkers of lupus nephritis histology and flare: deciphering the relevant amidst the noise. Nephrol Dial Transplant 32:i71-i79
Opotowsky, Alexander R; Baraona, Fernando R; Mc Causland, Finnian R et al. (2017) Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation. Heart 103:434-442
Hsu, Chi-Yuan; Xie, Dawei; Waikar, Sushrut S et al. (2017) Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression. Kidney Int 91:196-203

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