Rhubarb and ACE Inhibitor Study

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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.