Kidney fibrosis is a critical health problem in the United States because it represents the final common pathway of all chronic kidney diseases yet no biomarkers exist to aid in its diagnosis or measurement of progression. Using cutting edge genomic techniques, we have identified six novel biomarkers of kidney fibrosis and we hypothesize that levels of these biomarkers will accurately reflect kidney fibrosis in humans. In this proposal we have assembled three unique human patient cohorts in which to evaluate these six biomarkers, using histologic kidney fibrosis from kidney biopsy as the gold standard. We will measure biomarker levels in both serum and urine, using controlled and validated assays, and compare biomarker levels with the degree of tubulointerstitial fibrosis observed histologically. The most promising biomarkers will then be measured in a prospective chronic kidney disease cohort, comparing rapid progressors with those who do not progress. Our multidisciplinary team includes individuals with expertise in preclinical fibrosis models, assay development, molecular biology, regulatory compliance, clinical epidemiology, trial design and biostatistics. Together, the proposed experiments represent a rigorous evaluation of these six biomarkers in human chronic kidney disease and will pave the path forward for future studies that will transform clinical trial design and care in nephrology.
Kidney fibrosis is the leading cause of kidney failure worldwide and represents an enormous health burden and unmet medical need. New biomarkers are needed to quantify kidney fibrosis non-invasively in order to identify patients at risk of kidney disease progression and to facilitate clinical trial design. We have discovered six novel biomarkers of kidney fibrosis that are extremely promising for measurement of kidney fibrosis in humans. The experiments in this application are designed to evaluate these six biomarkers in three unique patient cohorts in order to define the biomarker with the greatest promise for future large scale qualification efforts, ideally in collaboration with NIH, regulatory agencies, and industry.
|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|
|Malone, Andrew F; Wu, Haojia; Humphreys, Benjamin D (2018) Bringing Renal Biopsy Interpretation Into the Molecular Age With Single-Cell RNA Sequencing. Semin Nephrol 38:31-39|
|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|
|Cardenas-Gonzalez, Mariana; Srivastava, Anand; Pavkovic, Mira et al. (2017) Identification, Confirmation, and Replication of Novel Urinary MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy. Clin Chem 63:1515-1526|
|Ó hAinmhire, Eoghainín; Humphreys, Benjamin D (2017) Fibrotic Changes Mediating Acute Kidney Injury to Chronic Kidney Disease Transition. Nephron 137:264-267|
|Wu, Haojia; Humphreys, Benjamin D (2017) The promise of single-cell RNA sequencing for kidney disease investigation. Kidney Int 92:1334-1342|
|Leaf, David E; Waikar, Sushrut S (2017) End Points for Clinical Trials in Acute Kidney Injury. Am J Kidney Dis 69:108-116|
|Pang, Paul; Abbott, Molly; Chang, Steven L et al. (2017) Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks. Kidney Int 91:129-143|
|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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