PANCREAS TRANSPLANTATION AND DIABETIC NEPHROPATHY

胰腺移植和糖尿病肾病

• 批准号: 3244978
• 负责人: MICHAEL W. STEFFES
• 金额: $ 12.09万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3244978
• 关键词: basement membrane; biopsy; blood flow measurement; blood glucose; blood pressure; diabetic nephropathy; electron microscopy; fluorescence microscopy; glomerular filtration rate; hemoglobin As; human subject; immunofluorescence technique; insulin dependent diabetes mellitus; kidney circulation; kidney function; kidney transplantation; mesangium; p aminohippurate; pancreas transplantation

Diabetic nephropathy poses a major life-threatening consequence for the patient with either type I or type II diabetes mellitus. Although glycemic control has been implicated in preventing or reversing the functional and structural manifestations of diabetic nephropathy (especially in experimental animals), the long-term effects of near-normal glycemic control on preventing or reversing the progression of diabetic renal lesions in man have not been rigorously examined. Pancreas transplantation to patients with type I diabetes mellitus provides the opportunity to effect long-term euglycemia under several venues: simultaneous pancreas and kidney transplantation alone. Studies of renal biopsies and renal function occurring at the time of pancreas transplantation and at 2 and 5 years (and in some cases 10 years) later yield quantitative morphometric analyses of glomerular structure and measures of glomerular filtration rate and renal blood flow. The primary endpoint in all cases will be the expansion of the glomerular mesangium by measuring its volume fraction and total volume in the glomerulus. Secondary endpoints include glomerular basement membrane width, mesangial matrix volume and measures of renal function. Three different specific aims can be addressed: the prevention of renal lesions of diabetic nephropathy with euglycemia established by concurrent pancreas/kidney transplantation; the halting or reversal of the progression of early renal lesions present in the previously transplanted kidney with subsequent pancreas transplantation; and the amelioration of established renal lesions in patients with their own kidneys who received pancreas transplantation alone. Diabetic and non-diabetic recipients of renal transplants alone constitute control groups with which to compare the results from the renal transplant recipients who also received pancreatic transplants, as do untreated diabetic patients when compared to recipients of pancreas transplants alone. Since pancreas transplantation has become a more frequently applied procedure to manage the patient with type I diabetes mellitus, the studies proposed will address the potential efficacy of the procedure in altering the course of diabetic nephropathy. With the extended period of time necessary to follow the course of diabetic renal disease, an immediate application of techniques to study diabetic renal disease and pancreas transplantation has the potential to address its efficacy in the shortest period of time and to contribute broadly to understanding the stage(s) of diabetic nephropathy ultimately benefiting from the establishment of a continuous euglycemic state.

糖尿病性肾病对 患有I型或II型糖尿病的患者。 虽然血糖 控制与防止或逆转功能有关和 糖尿病性肾病的结构表现（尤其是在 实验动物），近期血糖的长期影响 控制或逆转糖尿病肾脏的进展 没有严格检查人的病变。 胰腺移植 对于I型糖尿病的患者， 在几个场所下效果长期的葡萄糖：同时胰腺 仅肾脏移植。 肾脏活检和肾脏的研究 胰腺移植时发生的功能，在2和5 年（在某些情况下为10年）后来产生定量形态计量学 肾小球结构的分析和肾小球滤过率的测量 和肾血流。 在所有情况下，主要终点都将是 通过测量其体积分数和 肾小球中的总体积。 次要终点包括肾小球 地下膜宽度，肾小球矩阵体积和肾脏的测量 功能。 可以解决三个不同的特定目标：预防 糖尿病性肾病的肾脏病变与尤利克血症建立 并发胰腺/肾脏移植；停止或逆转 先前移植中存在的早期肾病变病变的进展 肾脏随后进行胰腺移植；和改善 在接受自己的肾脏的患者中建立的肾脏病变 仅胰腺移植。 糖尿病和非糖尿病接受者 仅肾脏移植构成对照组，以比较 肾移植接受者的结果，他们也接受了胰腺 移植，与接受者相比，未经治疗的糖尿病患者也是如此 仅胰腺移植。 由于胰腺移植已变得更加频繁地应用 治疗I型糖尿病的患者的程序，研究 提议的将解决该程序更改的潜在功效 糖尿病性肾病的过程。 长时间 遵循糖尿病肾脏疾病的过程，这是立即的 技术在研究糖尿病肾脏疾病和胰腺的应用 移植有可能在最短的 一段时间，并为理解阶段的贡献 糖尿病性肾病最终受益于建立 连续的尤金州状态。