Improving Outcomes in Diabetic Nephropathy

改善糖尿病肾病的治疗效果

• 批准号: 6665250
• 负责人: ROBERT Daniel TOTO
• 金额: $ 44.21万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665250
• 关键词: ACE inhibitors; aldosterone; angiotensin II; antihypertensive agents; blood lipid; blood pressure; clinical research; clinical trials; combination chemotherapy; creatinine; diabetes mellitus; diabetes mellitus therapy; diabetic nephropathy; diuretics; human subject; human therapy evaluation; kidney disorder chemotherapy; longitudinal human study; losartan; monitoring device; outcomes research; pathologic process; patient oriented research; potassium; proteinuria; renin; transforming growth factors; young adult human (21-34)

DESCRIPTION (provided by applicant): The long-range objective of this project is to prevent progression of diabetic nephropathy, the leading cause of end-stage renal disease (ESRD). In most patients diabetic nephropathy progresses inexorably to ESRD despite inhibition of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). The specific aims of this proposal are to: 1) recruit a multi ethnic cohort of 72 young adults (ages 20-40) with type 1 (n=36) or type 2 (n=36) diabetes and overt nephropathy (defined as a urine albumin/creatinine ratio > 300 mg albumin/g creatinine) and randomize in a double blind fashion to a control group consisting of ACEI-based therapy alone (ramipril 40 mg once daily) or one of two experimental groups: a) ACEI + ARB (ramipril 40 mg once daily plus Iosartan100 mg once daily) or b) ACEI + mineralocorticoid receptor antagonist (MRA) (ramipril40 mg once daily plus spironolactone 25 mg once daily); 2) conduct a 12-month prospective study to determine if proteinuria is reduced to a greater extent when either the ARB or MRA is added to ACEi-based therapy. This study is powered to detect a 40% greater reduction in 24-hour urine albumin/creatinine ratio in either experimental group versus control (alpha= 0.05, beta=0.20, repeated measures analysis of variance). Secondary endpoints to be examined include:(a) serum potassium and creatinine to assess safety, (b) TGF-beta, as a surrogate marker for ongoing renal injury, (c) plasma renin activity, angiotensin II and aldosterone levels and (d) plasma lipids and lipoprotein composition; and 3) perform repeated ambulatory blood pressure monitoring (ABPM) to examine the renoprotective effect of the 3 different regimens at comparable 24-hour BP of < 125/75 mmHg. The deliverables include: 1) documentation of the safety of maximal dose combination therapy; 2) the feasibility of utilizing 24-hr ABPM to establish BP independent renoprotective effects of specific antihypertensive therapies; and 3) provide preliminary data for future large-scale studies to test efficacy and safety of combining ACEi with MIRA therapy on renal outcomes.

描述（由申请人提供）：该项目的远距离目标是防止糖尿病性肾病的进展，糖尿病性肾病是终末期肾脏疾病（ESRD）的主要原因。在大多数患者中，尽管具有血管紧张素转化酶抑制剂（ACEIS）或血管紧张素II II型1型受体阻滞剂（ARBS）的血管紧张素抑制了肾素 - 血管紧张素 - 醛固酮系统，但糖尿病性肾病仍无法脱离为ESRD。 The specific aims of this proposal are to: 1) recruit a multi ethnic cohort of 72 young adults (ages 20-40) with type 1 (n=36) or type 2 (n=36) diabetes and overt nephropathy (defined as a urine albumin/creatinine ratio > 300 mg albumin/g creatinine) and randomize in a double blind fashion to a control group consisting of ACEI-based therapy alone （Ramipril每天每天40 mg）或两个实验组之一：A）ACEI + ARB（Ramipril 40 mg每天每天40 mg加上iosartan100毫克每天一次）或B）ACEI + ACEI +矿物皮质激素受体拮抗剂（MRA）（Ramipril40毫克每天每天每天一次加上螺丝酮25 mg一次）； 2）进行12个月的前瞻性研究，以确定当将ARB或MRA添加到基于ACEI的治疗中时，是否会更大程度地降低蛋白尿。这项研究有助于检测两种实验组与对照组中24小时尿白蛋白/肌酐比率的40％降低（alpha = 0.05，beta = 0.20，对方差的重复测量分析）。待检查的次要终点包括：（a）评估安全性的血清钾和肌酐，（b）TGF-β，作为持续肾脏损伤的替代标记，（c）血浆肾素活性，血管紧张素II和血管紧张素II和醛固酮水平以及（d）血浆脂质和脂质蛋白的组成； 3）进行反复的卧床血压监测（ABPM），以检查3种不同方案的肉变保护作用，可在24小时BP <125/75 mmHg时检查。可交付成果包括：1）最大剂量联合疗法安全性的文件； 2）利用24小时ABPM建立特定降压疗法的BP独立肾脏保护作用的可行性； 3）为将来的大规模研究提供初步数据，以测试ACEI与MIRA治疗在肾脏结局上的功效和安全性。