Abstract

Background: Add-on therapy with the Mineralocorticoid-Receptor-Antagonists (MRAs) spironolactone and eplerenone was shown to enhance the cardioprotective action of angiotensinconverting- enzyme-inhibitors (ACEIs), angiotensin-receptor-blockers (ARBs) and/or β-blockers in nondialysis patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction. The risk/benefit ratio of MRAs in dialysis patients is less well defined, owing to concerns that their cardioprotective actions may be counteracted by excess risk of hyperkalemia.

Methods: We performed a systematic literature search of MEDLINE/PubMed database (inception to September 15, 2016) to identify randomized controlled studies evaluating the effects of spironolactone and eplerenone on surrogate cardiovascular risk factors and clinical outcomes in patients receiving hemodialysis or peritoneal dialysis.

Results: A growing body of evidence derived from small randomized studies suggests that MRA therapy improves a number of surrogate cardiovascular risk factors (i.e. blood pressure, LV mass index, LV ejection fraction, carotid intima-media-thickness) in long-term dialysis patients. Two larger studies evaluating “hard” cardiovascular endpoints showed that these cardioprotective actions of MRAs are translated into a clinically relevant (up to 60%) reduction in the risk of all-cause and cardiovascular mortality. On the other hand, MRA use was shown to be accompanied by a parallel increase in the risk of hyperkalemia and gynecomastia.

Conclusion: Small, hypothesis-generating randomized trials support a cardioprotective role of MRA therapy in patients receiving hemodialysis or peritoneal dialysis. These promising results call for larger, properly-designed studies aiming to fully elucidate the potential harms and benefits of MRAs in this high-risk population. In anticipation of the results of ongoing outcome trials, the wide use of MRAs in dialysis patients should be avoided.

Keywords: Cardiovascular outcomes, ESRD, eplerenone, mineralocorticoid-receptor-antagonism, spironolactone, randomized controlled trials.

Graphical Abstract