Rhubarb and ACE Inhibitor Study

描述（由申请人提供）： 背景资料：患有终末期肾病（ESRD）的糖尿病患者接受肾脏替代治疗（RRT）（如透析和肾移植）的数量正在急剧增加。血管紧张素转换酶抑制剂（ACEI）在糖尿病肾病中的应用有助于减缓肾脏疾病的进展。为了实现更完整的长期肾保护，可能需要针对进行性肾损伤发病机制的不同方面采用多种疗法的综合策略。对中国慢性肾脏病患者残肾的实验研究和临床试验表明，大黄治疗对预防慢性肾脏病（CKD）进展有益。单独使用时，大黄的作用与ACEI相当。当联合使用时，大黄的肾保护作用似乎是ACEI的添加剂。大黄对肾功能的作用机制尚不清楚，但动物研究表明，大黄抑制TGF β和TNF α，从而防止CKD的进展。 设计图：本研究是一项随机双盲安慰剂对照试验，旨在检查大黄对60例糖尿病肾病患者的影响。 目的：确定大黄和依那普利（n=30）与依那普利和安慰剂（n=30）相比对（a）白蛋白尿（肾小球损伤的替代标记物）（B）肾小球滤过率的下降速率（如通过碘他仑清除率测量的）（c）血清和尿TGF β的联合作用。 方法：参与者将被随机分配到接受依那普利和安慰剂的“对照组”，而接受依那普利和大黄的“干预组”，为期2年。大黄的起始剂量为1 g/d，如果耐受良好，则在8周的时间内，如果GFR <40 ml/min，则剂量将增加至4 g/d，如果GFR>40 ml/min，则剂量将增加至6 g/d，并且相同剂量将持续至研究结束。最大剂量将增加至20 mg/天。将调整BP药物，以维持K-DOQI推荐的BP目标指南。有腹泻，肾结石，高钾血症的风险。将进行血液和尿液检查，以监测安全性和疗效。

DESCRIPTION (provided by applicant): Background: The number of diabetic patients with end stage renal disease (ESRD) receiving renal replacement treatments (RRT) such as dialysis and kidney transplant is increasing dramatically. The use of angiotensin converting enzyme inhibitors (ACEI) in diabetic nephropathy has helped in slowing renal disease progression. To achieve more complete long term renoprotection, a comprehensive strategy employing multiple therapies directed at different aspects of the pathogenesis of progressive renal injury is likely required. Experimental studies on remnant kidneys and clinical trials in chronic kidney disease patients from China suggest that rhubarb treatment exerts a beneficial on the prevention of progression of chronic kidney disease (CKD). When used alone, rhubarb had effects equivalent to that of ACEI. When used in combination, the renoprotective effect of rhubarb appears to be additive to ACEI The mechanism of action of rhubarb on renal function is not clearly known but animal studies suggest that rhubarb inhibits TGFbeta and TNFalpha thereby preventing the progression of CKD. Design: This study is a randomized double-blind placebo-controlled pilot trial designed to examine the effect of rhubarb in 60 patients with diabetic nephropathy. Aims: To determine the combined effect of rhubarb and enalapril (n=30) compared to enalapril and placebo (n=30) on (a)albuminuria, a surrogate marker for glomerular injury (b) the rate of decline of glomerular filtration rate as measured by iothalamte clearance (c) serum and urine TGFbeta. Method: Participants will be randomized either to "Control arm" receiving enalapril and placebo whereas the "intervention arm" receiving enalapril and rhubarb for 2 years. The starting dose of rhubarb will be 1 g/d and if tolerated well, then the dose will be incremented to 4 g/d if the GFR <40ml/min and to 6 g/d if the GFR is >40 ml/min over a period of 8 weeks, and the same dose will be continued till the end of the study.Enalapril will be initiated at 10mg/day and if tolerated, it will be increased to a maximum dose of 20 mg/day. The BP medications will be adjusted to maintain the K-DOQI recommended guidelines for BP goals. Risks are diarrhea, kidney stones, hyperkalemia. Blood and urine tests will be done to monitor safety and efficacy.