Diabetic Nephropathy

糖尿病肾病

• 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
• 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

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1型糖尿病（D）患者（pts）的大胰腺（PTx）和肾脏（KTx）移植人群，以更好地了解糖尿病肾病（DN），肾衰竭的主要原因。目标是：（a）确定PTx是否可以更容易地阻止或逆转早期与更确定的DN病变;（B）继续研究DN中的肾结构-功能关系，重点是多方面的病理性DN病变，包括肾小球、血管、间质病变， 肾小球-肾小管连接;（c）继续研究DN的自然史和 肾活检在预测预后中的作用;（d）定量和了解肾小管功能不全的基础 （e）阐明DN中肾小球（肾小球）上皮细胞异常;（f） 研究DN患者肾小球细胞外基质异常情况;（g）研究DN患者的复发情况， （h）研究DN的分子/遗传基础并开发DN风险的细胞标志物; (i)确定环孢菌素（CSA）的长期（10-15年）结构后果， PTx接受者的原生肾脏;以及（j）确定PTx的短期（5年）后果， PTx接受者的自体肾脏上的BMF，并将其与CSA治疗5年后观察到的结果进行比较。总之，这些研究将有助于阐明DN的发病机制和自然史，解开这种疾病的分子和遗传方面的一些，描述在PTx患者的DN逆转的动力学，并在KTx患者的复发和扩大我们的知识的钙质沉着抑制剂的肾毒性作用。