Biomarkers of Chronic Kidney Disease

慢性肾脏病的生物标志物

• 批准号: 9528223
• 负责人: JOSEPH VINCENT BONVENTRE
• 金额: $ 25万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9528223
• 关键词: Acute; Adult; Affect; Albuminuria; Ancillary Study; Animal Model; Biological Assay; Biological Markers; Biopsy; Blood; Boston; Cardiovascular Diseases; Chronic; Chronic Kidney Failure; Cohort Studies; Collaborations; Communities; Complement; Complement Activation; Data; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease Progression; End stage renal failure; Ensure; Epidemiology; Epithelial Cells; Fibrosis; Framingham Heart Study; Functional disorder; Future; Glycoproteins; Histopathology; Hospitals; Incidence; Individual; Inflammation; Inflammatory; Injury; Injury to Kidney; Insulin-Dependent Diabetes Mellitus; Investigation; Kidney; Kidney Diseases; Kidney Failure; Laboratories; Lead; Longitudinal Studies; Measurement; Measures; Natural Immunity; Non-Insulin-Dependent Diabetes Mellitus; Participant; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Pima Indian; Plasma; Play; Population; Prospective Studies; Prospective cohort study; Quality Control; Renal function; Renin-Angiotensin System; Research; Risk; Risk Factors; Rodent; Role; Sampling; Serum; Site; Stimulus; Study of serum; Sweden; TNFRSF1A gene; Testing; Time; Tubular formation; Urine; Validation; Woman; aged; base; clinically relevant; cohort; cost; design; diabetic; follow-up; functional decline; human data; men; mortality; nephrotoxicity; non-diabetic; novel marker; outcome forecast; prospective; public health relevance; rat KIM-1 protein; response; therapy development; urinary

 DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) affects >10% of the adult US population, costs tens of billions of dollars annually, and can lead to progressive kidney failure, cardiovascular disease (CVD), and early mortality. Although we understand much about the epidemiology of CKD, the underlying mechanisms of CKD initiation and progression remain less well understood. In this proposal, which represents a continuation of Phase 1 of the CKD Biomarker Consortium, we seek to test the ability of promising biomarkers of kidney injury to predict CKD incidence and progression in non-proteinuric and proteinuric individuals; furthermore, we propose serving as a development, quality control, and validation site for biomarker measurements for the Consortium. We propose measurement of novel biomarkers of tubular injury and inflammation, two key pathways of injury that we hypothesize are associated with CKD progression in both diabetic- and non-diabetic kidney disease. Biomarkers to be tested included kidney injury molecule-1, a transmembrane glycoprotein expressed almost exclusively in the proximal tubule in response to injurious stimuli; urinary complement fragments, which were identified as promising biomarkers in Phase 1 of CKD BioCon; and soluble tumor necrosis factor-a receptors 1 and 2 (sTNFR1 and sTNFR2). We will measure biomarkers approved by the Consortium and external expert panel in unique prospective cohort studies: the Framingham Heart Study (FHS), a prospective study of over 2,948 individuals with available baseline plasma samples and follow-up data over more than one decade; two other community-based cohort studies from Uppsala, Sweden, ULSAM (N = 778) and PIVUS (N = 815); the Renin-Angiotensin System Study (RASS), comprised of 254 T1D participants aged 16-65 years who underwent kidney biopsy for research purposes at baseline and after 5 years of follow-up with blood and urine samples collected every six months; the Pima Indian Cohort of 260 participants (111 biopsied at end of study) with type 2 diabetes mellitus (T2D) with available plasma and urine samples collected every two years during a median follow-up of 10 years; and the Boston Kidney Biopsy Cohort (U01DK093574, ancillary study to CKD Biomarkers Consortium), an ongoing prospective study (N = 649 to date) in which blood and urine samples are obtained at the time of native kidney biopsy. In Aim 1 we will test whether biomarkers, independently of albuminuria and eGFR, are associated with future development of incident CKD or CKD progression. In Aim 2, we will test the associations of biomarkers with histopathologic findings on kidney biopsy. In Aim 3, we propose establishing Brigham and Women's Hospital as a core laboratory for biomarker measurements for the Consortium and to continue of our efforts to ensure reliable quality control and validation of assays in use across the Consortium.

 描述（由适用提供）：慢性肾脏疾病（CKD）影响> 10％的美国人口，每年成本数十亿美元，并可能导致渐进的肾衰竭，心血管疾病（CVD）和早期死亡率。尽管我们对CKD的流行病学有很多了解，但CKD计划和进展的潜在机制仍然不太了解。在代表CKD生物标志物联盟1阶段的延续的该提案中，我们试图测试肾损伤的承诺生物标志物预测非蛋白尿和蛋白尿个体中CKD的进展和进展的能力；此外，我们建议作为财团生物标志物测量的开发，质量控制和验证地点。我们提出了对肾小管损伤和感染的新生物标志物的测量，我们假设的两种关键损伤途径与糖尿病和非糖尿病肾脏疾病的CKD进展有关。要测试的生物标志物包括肾脏损伤分子1，跨膜糖蛋白几乎完全在近端小管中表达，以响应损伤刺激。尿量补体片段，在CKD Biocon的第1阶段被确定为有前途的生物标志物；和实体瘤坏死因子A受体1和2（STNFR1和STNFR2）。我们将测量由财团和外部专家小组批准的独特前瞻性队列研究中的生物标志物：弗雷明汉心脏研究（FHS），这是一项针对2,948多名具有可用基线等离子体样本和后续数据的前瞻性研究；来自Uppsala，瑞典，Ulsam（n = 778）和Pivus（n = 815）的另外两项基于社区的队列研究；肾素 - 血管紧张素系统研究（RASS）由254名T1D参与者组成16-65岁的参与者，他们在基线时进行了研究目的进行肾脏活检，并在接受每六个月收集的血液和尿液样本进行了5年的随访之后； PIMA印度人队列的260名参与者（研究结束时进行了111个活检）与2型糖尿病（T2D），可用的血浆和尿液样本在10年的中位随访期间每两年收集一次；以及波士顿儿童活检队列（U01DK093574，辅助研究CKD生物标志物联盟），这是一项正在进行的前瞻性研究（迄今为止n = 649），在该研究中，在本地肾脏活检时获得了血液和尿液样品。在AIM 1中，我们将测试与蛋白尿和EGFR无关的生物标志物是否与事件CKD或CKD进展的未来发展有关。在AIM 2中，我们将测试生物标志物与肾脏活检的组织病理学发现的关联。在AIM 3中，我们建议建立杨百翰和妇女医院，作为财团生物标志物测量的核心实验室，并继续我们的努力，以确保可靠的质量控制和对整个财团使用的测定法进行验证。