Antibody Microarray Predicting Pima Diabetic Nephropathy

预测 Pima 糖尿病肾病的抗体微阵列

基本信息

批准号：
6936691
负责人：
RAVI THADHANI
金额：
$ 13.75万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2006-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Diabetic Nephropathy (DN) is the most common cause of end stage renal disease in the United States. Among patients with type 2 diabetes (T2DM), microalbuminuria is not a strong risk factor for developing DN, and thus early identification of those at risk for DN has been challenging. Pro-inflammatory cytokines are biologically linked to DN, and cytokines acting locally in the kidney and evident in the urine may identify those with T2DM at risk for DN. Although cross-sectional studies suggest urine and not serum cytokines are altered at the time of DN, prospective studies are limited. Furthermore, prior studies examined single urine cytokine alterations, which may not best characterize this complex disorder. In fact, a specific combination of cytokines ('cytokine signatures') may better identify those at risk for DN. A study of subjects at high risk for DN with urine samples collected prospectively and tested with novel multiplexed profiling techniques overcomes these previous limitations. Pima Indians have a high rate of developing T2DM and DN. Since 1965, a cohort of Pima Indians has been followed biennially by the NIDDK. Utilizing a comprehensive database in conjunction with urine samples collected at each biennial visit, we will test two hypotheses: 1) Specific urine cytokines (TNF-alpha, TGF-beta, MCP-1, IL-6, IL-8, and IL-18) are altered 10 years before the onset of macroalbuminuria, when subjects display normoalbuminuria; and 2) A disease specific cytokine microarray identifying those at risk for DN can be developed. In collaboration with NIDDK, we have identified a nested group of cases and matched (to minimize confounding) controls with urine samples collected at baseline and 10 years thereafter. To test our hypotheses, we have assembled a multidisciplinary team with expertise in diabetes and diabetic nephropathy, nested case-control studies, protein array technology, and bioinfromatics. This R21 proposal may provide insight into the pathogenesis of DN, provide useful biomarkers to predict DN, and suggest early targets for intervention for this devastating disorder.

描述（由申请人提供）：糖尿病性肾病（DN）是美国最常见的末期肾脏疾病的原因。在2型糖尿病（T2DM）的患者中，微量白蛋白尿并不是发展DN的强大危险因素，因此，早期鉴定出患有DN危险的患者是具有挑战性的。促炎性细胞因子在生物学上与DN相关，并且在肾脏中作用并在尿液中明显作用的细胞因子可能识别患有DN风险的T2DM的细胞因子。尽管横断面研究表明尿液而不是血清细胞因子在DN时改变，但前瞻性研究受到限制。此外，先前的研究检查了单尿细胞因子的改变，这可能不是最能表征这种复杂疾病的特征。实际上，细胞因子（“细胞因子特征”）的特定组合可以更好地识别有DN风险的细胞因子。一项针对前瞻性收集尿液样本DN风险的受试者的研究，并通过新颖的多重分析技术进行了测试，克服了这些先前的局限性。 PIMA印第安人开发T2DM和DN的率很高。自1965年以来，NIDDK每两年一次跟随PIMA印第安人队。利用一个全面的数据库与每次两年一次的访问时收集的尿液样本结合在一起，我们将测试两个假设：1）特定的尿液细胞因子（TNF-Alpha，TGF-BETA，TGF-BETA，MCP-1，IL-6，IL-6，IL-8和IL-18）在10年之前进行了10年的变化。 2）可以开发出一种特异性细胞因子微阵列，以识别有DN风险的疾病。与NIDDK合作，我们确定了一组嵌套的病例，并与在基线时收集的尿液样本和此后10年收集的尿液样本进行了匹配（以最大程度地减少混淆）。为了检验我们的假设，我们组建了一个具有糖尿病和糖尿病肾病，嵌套病例对照研究，蛋白质阵列技术和生物毒素的糖尿病性肾病专业知识的多学科团队。该R21提案可以提供有关DN的发病机理的洞察力，提供了有用的生物标志物来预测DN，并建议对这种毁灭性疾病进行干预的早期靶标。