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Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease: A Systematic Review and Meta-analysis

Sankar D. Navaneethan^*,, Sagar U. Nigwekar, Ashwini R. Sehgal, and Giovanni F.M. Strippoli^,||,¶,**

^* Department of Nephrology and Hypertension, Glickman Institute of Urological and Kidney Diseases, Cleveland Clinic, Cleveland, Ohio; Department of Medicine, Rochester General Hospital, Rochester, New York; Division of Nephrology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio; ^|| Department of Pharmacology and Clinical Epidemiology, Mario Negri Sud Consortium, S. Maria Imbaro, Italy; ^¶ Diaverum Corporate Medical Scientific Office, Lund Sweden; Cochrane Renal Group, Sydney, Australia; ^** School of Public Health, University of Sydney, Sydney, Australia

Correspondence: Dr. Sankar D. Navaneethan, Department of Nephrology and Hypertension, Cleveland Clinic, 9500 Euclid Avenue, Q7–155, Cleveland, Ohio 44195. Phone: +1 216 444 8415; Fax: +1 216 444 9378; E-mail: navanes{at}ccf.org

Background and objectives: Addition of aldosterone antagonists (AA) might provide renal benefits to proteinuric chronic kidney disease (CKD) patients over and above the inhibition of renin-angiotensin system blockers (RAS). We evaluated the benefits and harms of adding selective and nonselective AA in CKD patients already on RAS.

Design, setting, participants, & measurements: MEDLINE, EMBASE, and Renal Health Library were searched for relevant randomized clinical trials in adult CKD patients. Results were summarized using the random-effects model.

Results: Eleven trials (991 patients) were included. In comparison to angiotensin- converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) plus placebo, nonselective AA along with ACEi and/or ARB significantly reduced 24 h proteinuria (seven trials, 372 patients, weighted mean difference [WMD] –0.80 g, 95% CI –1.27, –0.33) and BP. This did not translate into an improvement in GFR (WMD –0.70 ml/min/1.73m², 95% CI –4.73, 3.34). There was a significant increase in the risk of hyperkalemia with the addition of nonselective AA to ACEi and/or ARB (relative risk 3.06, 95% CI 1.26, 7.41). In two trials, addition of selective AA to ACEi resulted in an additional reduction in 24 h proteinuria, without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available in any of the trials.

Conclusions: Aldosterone antagonists reduce proteinuria in CKD patients already on ACEis and ARBs but increase the risk of hyperkalemia. Long-term effects of these agents on renal outcomes, mortality, and safety need to be established.

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