Renoprotection In Type 2 Diabetes Mellitus

2 型糖尿病的肾脏保护

• 批准号: 7153444
• 负责人: ROBERT G NELSON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7153444
• 关键词: Native Americans; albuminuria; angiotensin receptor; biomarker; biopsy; clinical trials; diabetes mellitus therapy; diabetic nephropathy; disease /disorder prevention /control; drug screening /evaluation; glomerular filtration rate; glomerulosclerosis; human subject; human therapy evaluation; kidney disorder chemotherapy; lisinopril; longitudinal human study; losartan; medical complication; morphometry; noninsulin dependent diabetes mellitus; outcomes research; patient oriented research; podocyte

The purpose of this project is to identify treatments to prevent or slow the rate of progression of renal disease in type 2 diabetes mellitus in the Pima Indians. The efficacy of the angiotensin-converting-enzyme inhibitor (ACEi) lisinopril is being tested in 20 Pima Indians with overt diabetic kidney disease. Glomerular function was measured in each subject for about 4 years prior to treatment with lisinopril and it will be measured at 6-monthly intervals during treatment. Measurements of glomerular function will continue until the onset of renal failure, and changes in glomerular function before and after initiation of lisinopril treatment will be examined. A randomized, double-blinded, placebo-controlled clinical trial is being conducted in 170 diabetic Pima Indians with normal urinary albumin excretion or microalbuminuria to determine whether blockade of the angiotensin II receptor with losartan will prevent or attenuate the development and progression of early diabetic nephropathy. Kidney biopsies will be performed after 6.5 years in all subjects. Morphometric analysis of kidney biopsies will be used to determine differences in the prevalence of global sclerosis, the number of visceral epithelial cells per glomerulus, and the breadth of epithelial foot processes between treatment groups. Differences in a severity index computed from the joint distribution of these morphometric variables will be used to assess the renoprotective efficacy of losartan at the tissue level. Particular attention will be paid to podocyte biology, since loss of podocytes appears to be an important factor in the progression of kidney disease in diabetes. Treatment will continue until subjects reach the primary endpoint, a GFR of 60 ml/min or less or a decline in GFR to half the baseline value in those that entered the study with a GFR of less than 120 ml/min. The trial will end prior to reaching the primary endpoint if there is sufficient evidence to draw conclusions regarding the renoprotective efficacy of losartan based on the morphometric analysis of the kidney biopsy specimens. Follow-up of all patients will continue after the randomized portion of the trial is completed. Patients will be followed till death or development of end-stage renal disease, whichever comes first, with annual measures of glomerular function. These projects, in part, represent extensions of work previously reported as Project Number Z01 DK 69037.

该项目的目的是识别治疗方法，以预防或减缓皮马印第安人2型糖尿病中肾脏疾病进展的速度。血管紧张素转化 - 酶抑制剂（ACEI）赖诺普利的疗效正在患有20种具有明显的糖尿病肾脏疾病的PIMA印第安人中。在用赖诺普利治疗之前，在每个受试者中测量了大约4年的肾小球功能，并将在治疗过程中以6个月的间隔进行测量。肾小球功能的测量将一直持续到肾衰竭的发作，并在林诺普利治疗开始之前和之后的肾小球功能的变化将被检查。在170名具有正常尿白蛋白排泄或微珠蛋白尿的糖尿病PIMA印第安人中，正在进行一项随机，双盲，安慰剂对照试验，以确定用losartan封锁血管紧张素II受体是否会预防或减轻早期的糖尿病源性肾上腺素源性的发育和进展。肾脏活检将在所有受试者的6。5年后进行。肾脏活检的形态分析将用于确定全球硬化症患病率的差异，每个肾小球的内脏上皮细胞的数量以及治疗组之间上皮脚步过程的广度。从这些形态计量变量的联合分布计算出的严重程度指数的差异将用于评估Losartan在组织水平上的肾脏保护功效。由于足细胞的丧失似乎是糖尿病肾脏疾病进展的重要因素，因此特别关注足细胞生物学。治疗将继续进行，直到受试者达到主要终点为止，GFR的GFR为60 mL/min，或者在GFR少于120 mL/min的研究中，GFR的GFR或GFR下降到基线值的一半。如果有足够的证据根据肾脏活检标本的形态计量学分析得出有关氯沙坦肾脏保护功效的结论，则该试验将在达到主要终点之前结束。试验的随机部分完成后，所有患者的随访将继续。将遵循患者，直到死亡或终末期肾脏疾病的发展，以肾小球功能的年度措施为例。这些项目部分代表了先前报道为项目编号Z01 DK 69037的工作扩展。