Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review
Received 25 June 2007; accepted 31 October 2007.
Background
The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled.
Study Design
We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists.
Setting & Population
Adult patients with chronic kidney disease and proteinuria.
Selection Criteria for Studies
English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease.
Intervention
MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease.
Outcomes
Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes.
Results
15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively.
Limitations
Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias.
Conclusions
Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function, routine use of MRBs as additive therapy in patients with chronic kidney disease cannot be recommended yet. However, the findings of this review promote interesting hypotheses for future study.
1Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
2Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Address correspondence to Andrew S. Bomback, MD, University of North Carolina Kidney Center, 7024 Burnett-Womack Bldg, Campus Box 7155, Chapel Hill, NC 27599-7155.
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