Effects of renin-angiotensin system blockers on renal outcomes and all-cause mortality in patients with diabetic nephropathy: An updated meta-analysis

BACKGROUND In contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy. METHODS A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model. RESULTS Of the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% Cl 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% Cl 0.56-0.91 for ACEIs and RR 0.79; 95% Cl 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% Cl 0.85-1.09 for ACEls and RR 0.99; 95% Cl 0.85-1.16 for ARBs). CONCLUSION Treatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.