Diabetic Nephropathy

糖尿病肾病

基本信息

批准号：
7550706
负责人：
MICHAEL S MAUER
金额：
$ 13.3万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7550706
关键词：
Address Adhesions Allografting Atrophic Biochemical Biopsy Blood Vessels Calcinosis Candidate Disease Gene Clinical Controlled Study Cyclosporine Cyclosporins Development Diabetic Nephropathy Disease Disease regression Dose Epithelial Cells Excision Extracellular Matrix FK506 Failure Fibroblasts Fibrosis Focal Segmental Glomerulosclerosis Gene Expression Genes Genetic Glomerular Filtration Rate Individual Inpatients Insulin-Dependent Diabetes Mellitus Islets of Langerhans Transplantation Kidney Kidney Failure Kidney Transplantation Knowledge Lesion Long-Term Effects Membrane Messenger RNA Molecular Genetics Natural History Nature Nephrotoxic Numbers Outcome Pancreas Pancreas Transplantation Pathogenesis Pathologic Patients Pattern Population Predictive Value Production Prograf Proteinuria Rate Recurrence Resistance Risk Risk Factors Role Skin Staging Structure Tacrolimus Time Transplantation Tubular formation base cell injury glomerular basement membrane glomerulosclerosis inhibitor/antagonist interstitial kidney allograft mRNA Expression type I diabetic vasoconstriction

项目摘要

These continuation studies focus on large pancreas (PTx) and kidney (KTx) transplant populations of type 1 diabetic (D) patients (pts) in order to better understand diabetic nephropathy (DN), the leading cause of renal failure. Objectives are: (a) to determine whether PTx can more readily arrest or reverse the early vs. the more established lesions of DN; (b) to continue studies of renal structural-functional relationships in DN, with emphasis on the multifaceted pathologic DN lesions, including glomerular, vascular, interstitial lesions and glomerular-tubular connections; (c) to continue studies of DN natural history and the role of renal biopsy in predicting outcome; (d) to quantitate and understand the basis of atubular glomeruli (AG) in DN; (e) to elucidate glomerular (glom) epithelial cell abnormalities in DN; (f) to study the glom extracellular matrix abnormalities of DN; (g) to study the recurrence of DN in the KTx; (h) to study the molecular/genetic basis of DN and develop cellular markers of DN risk; (i) to determine the long-term (10-15 yr) structural consequences of cyclosporine (CSA) on the 'native kidneys of PTx recipients; and (j) to determine the shorter-term (5 yr) consequences of Prograf on the native kidneys of PTx recipients and compare these with those seen after 5 years of CSA treatment. Together, these studies will help to elucidate the pathogenesis and natural history of DN, unravel some of the molecular and genetic aspects of this disease, describe the dynamics of DN reversal in PTx pts, and recurrence in KTx pts and expand our knowledge of the nephrotoxic effects of calcinosis inhibitors.

这些继续研究的重点是大型胰腺（PTX）和肾脏（KTX）1型糖尿病患者（D）患者（PTS）的移植种群，以便更好地了解肾衰竭的主要原因糖尿病性肾病（DN）。目标是：（a）确定PTX是否可以更容易逮捕或扭转早期与较成熟的DN病变；（b）继续研究DN中的肾脏结构功能关系，重点是多方面的病理DN病变，包括肾小球，血管，间质性病变和肾小球管连接；（c）继续研究DN自然史和预测预后的肾脏活检；（d）定量和理解atubular的基础 DN中的肾小球（Ag）；（E）阐明DN中的肾小球（Glom）上皮细胞异常；（f）研究DN的Glom细胞外基质异常；（g）研究dn的复发 KTX; （H）研究DN的分子/遗传基础并发展DN风险的细胞标记；（i）确定环孢菌素（CSA）对长期（10 - 15年）的结构后果 'PTX接受者的本地肾脏；（j）确定较短的（5年）的后果 Prograf对PTX受体的本地肾脏，并将其与5年CSA治疗后看到的肾脏进行比较。这些研究将有助于阐明DN的发病机理和自然历史，揭示该疾病的某些分子和遗传方面，描述PTX PTS中DN反转的动力学，以及KTX PT中的复发并扩大我们对肾毒性的了解钙化抑制剂的作用。