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.