Background: Treatment with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). But some patients do not attain complete resolution of proteinuria and might have higher aldosterone levels within few months of treatment. The addition of aldosterone antagonists may be beneficial to these patients for reduction of progression of renal damage.
Objectives: We evaluated the benefits and harms of adding aldosterone antagonists in patients with CKD currently treated with ACEi and/or ARB.
Search strategy: We searched MEDLINE, EMBASE, CENTRAL, and hand-searched reference lists of textbooks, articles and scientific proceedings for relevant articles.
Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing aldosterone antagonists in addition to ACEi and/or ARB versus ACEi and/or ARB alone were included.
Data collection and analysis: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and heterogeneity was tested formally using the Cochran Q and I(2) statistic. Results were expressed as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI).
Main results: Ten studies (845 patients) were included. Compared to ACEi and/or ARB plus placebo, non-selective aldosterone antagonists along with ACEi and/or ARB significantly reduced 24 hour proteinuria (7 studies, 372 patients; MD -0.80 g, 95% CI -1.23 to -0.38). There was a significant reduction in both systolic and diastolic blood pressure at the end of treatment with the addition of non-selective aldosterone antagonists to ACEi and/or ARB. This did not translate into an improvement in glomerular filtration rate (5 studies, 306 patients; MD -0.70 mL/min/1.73 m(2), 95% CI -4.73 to 3.34). There was a significant increase in the risk of hyperkalaemia with the addition of non-selective aldosterone antagonists to ACEi and/or ARB (8 studies, 436 patients; RR 3.06, 95% CI 1.26 to 7.41). In two studies, the addition of selective aldosterone antagonists to ACEi resulted in an additional reduction in 24 hour proteinuria but without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available.
Authors' conclusions: Aldosterone antagonists contribute to reduction of proteinuria in patients with CKD who are already on ACEi and ARB but increase the risk of hyperkalaemia. Available studies are small and have short follow-up. Long-term effects on renal outcomes, mortality and safety are unknown.