Novel Human Biomarkers of Kidney Fibrosis

描述（由申请人提供）：肾纤维化在美国是一个严重的健康问题，因为它代表了所有慢性肾脏疾病的最终共同途径，但不存在生物标志物来帮助其诊断或测量进展。使用最先进的基因组技术，我们已经确定了六种新的肾纤维化生物标志物，我们假设这些生物标志物的水平将准确反映人类的肾纤维化。在该提案中，我们收集了三个独特的人类患者队列，其中使用来自肾脏活检的组织学肾纤维化作为金标准来评估这六种生物标志物。我们将使用受控和经验证的检测方法测量血清和尿液中的生物标志物水平，并将生物标志物水平与组织学观察到的肾小管间质纤维化程度进行比较。最有希望的生物标志物将在一个前瞻性的慢性肾脏疾病队列中进行测量，比较快速进展者与未进展者。我们的多学科团队包括在临床前纤维化模型、检测开发、分子生物学、法规遵从性、临床流行病学、试验设计和生物统计学方面具有专业知识的人员。总之，拟议的实验代表了对人类慢性肾脏疾病中这六种生物标志物的严格评估，并将为未来的研究铺平道路，这些研究将改变肾脏病学的临床试验设计和护理。

DESCRIPTION (provided by applicant): 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.