Antihypertensive agents for primary prevention of diabetic nephropathy

The objective of this study was to evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria. Randomized, controlled trials that compared any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and normoalbuminuria (albumin excretion rate <30 mg/d) were identified on Medline, in Embase, on the Cochrane Controlled Trials Register, in conference proceedings, and by contacting investigators. Two authors independently extracted data on renal outcomes and other patient-relevant outcomes (e.g., mortality, serious cardiovascular events) and assessed quality of trials. Analysis was by a random-effects model, and results were expressed as relative risk (RR) and 95% confidence intervals (CI). Sixteen trials (7603 patients) were identified, six of angiotensin-converting enzyme inhibitors (ACEi) versus placebo, six of ACEi versus calcium antagonists, one of ACEi versus calcium antagonists or combined ACEi and calcium antagonist, and three of ACEi versus other agents. Compared with placebo, ACEi significantly reduced the development of microalbuminuria (six trials, 3840 patients; RR 0.60; 95% CI 0.43 to 0.84) but not doubling of creatinine (three trials, 2683 patients; RR 0.81; 95% CI 0.24 to 2.71) or all-cause mortality (four trials, 3284 patients; RR 0.81; 95% CI 0.64 to 1.03). Compared with calcium antagonists, ACEi significantly reduced progression to microalbuminuria (four trials, 1210 patients; RR 0.58; 95% CI 0.40 to 0.84). A significant reduction in the risk for developing microalbuminuria in normoalbuminuric patients with diabetes has been demonstrated for ACEi only. It seems that the effect of ACEi is independent of baseline BP, renal function, and type of diabetes, but data are too sparse to be confident that these are not important effect modifiers, and an individual patient data meta-analysis is required.