Journal of Nephrology & Therapeutics

Effects of Dual Blockade of the Renin Angiotensin System in Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

Abstract

Jacqueline T. Pham ,Brian P. Schmitt ,David J. Leehey *

Objective: There is substantial evidence for a renoprotective effect of inhibitors of the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). However, it is unclear whether dual RAS blockade has additional benefits when compared to monotherapy in this population and whether any benefits outweigh the risks.

Data sources: A systematic review and meta-analysis of English language articles was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane database of systematic reviews.

Study selection: All randomized, controlled trials comparing RAS blockade to monotherapy in patients with overt proteinuria were included.

Data extraction: Articles were reviewed independently by two of the authors using a standardized data collection form including study quality indicators.

Data synthesis: All pooled analyses were based on random-effects models. The primary efficacy outcome measure was the percent reduction in proteinuria with combination therapy versus monotherapy measured by difference in means. Secondary outcomes included changes in systolic blood pressure (SBP), glomerular filtration rate (GFR), and serum potassium, and incidence of hyperkalemia. The primary safety outcome was hyperkalemia.

Results: Compared to monotherapy, combination therapy with an angiotensin converting enzyme inhibitor (ACEI) plus angiotensin receptor blocker (ARB) reduced proteinuria by an additional 25% (mean difference -25, 95% CI -33,- 17), whereas combination therapy with an aldosterone antagonist (ALDOA) plus ACEI or ARB reduced proteinurea by an additional 32% (mean difference -32, 95% CI -37,-27). SBP after treatment with combination therapy vs. monotherapy was significantly lower with both the ACEI/ARB and ALDOA combinations. Dual therapy was associated with an increase in serum potassium, in particular with the ALDOA combination.

Limitations: Most studies were small and of short duration, and none included major patient outcome data such as kidney failure or death.

Conclusion: Dual RAS blockade in patients with DKD reduces proteinuria and SBP but increases the risk of hyperkalemia.