Rhubarb and ACE Inhibitor Study

描述(由申请人提供)： 背景：糖尿病合并终末期肾病(ESRD)患者接受肾脏替代治疗(RRT)的人数急剧增加，如透析和肾移植。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脏保护，可能需要针对进行性肾损伤发病机制的不同方面采取综合策略，采用多种治疗方法。中国对慢性肾脏病残肾的实验研究和临床试验表明，大黄具有预防慢性肾脏病进展的作用。单独使用时，大黄的效果与ACEI相当。当大黄与血管紧张素转换酶抑制剂合用时，其肾脏保护作用似乎与血管紧张素转换酶抑制剂相加。大黄对肾功能的作用机制尚不清楚，但动物研究表明，大黄可抑制转化生长因子β和肿瘤坏死因子α，从而阻止CKD的进展。 设计：本研究是一项随机、双盲、安慰剂对照的先导试验，旨在观察大黄对60例糖尿病肾病患者的疗效。 目的：确定大黄和依那普利(n=30)与依那普利和安慰剂(n=30)对(A)蛋白尿(肾小球损伤的替代标志物)的联合作用(B)肾小球滤过率下降的速度(用硫蛋白清除率(C)血和尿中的转化生长因子β来衡量)。 方法：受试者随机分为对照组和干预组，对照组接受依那普利和安慰剂治疗，干预组接受依那普利和大黄治疗，为期2年。大黄的起始量为1g/d，如果耐受性良好，则剂量将增加到4g/d，如果GFR为40ml/min，则剂量将增加到6g/d，持续8周。同样的剂量将持续到研究结束。依那普利将以10 mg/d开始，如果耐受性良好，将增加到最大剂量20 mg/d。BP药物将进行调整，以维持K-DOQI推荐的BP目标指南。风险有腹泻、肾结石、高钾血症。将进行血液和尿液测试，以监测安全性和有效性。

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.