Although mineralocorticoid receptor (MR) antagonism is a mechanistically plausible target of therapy in patients with kidney failure, prior small trials failed to elucidate the safety and efficacy of spironolactone and eplerenone in this population. More conclusive evidence was provided by the ALCHEMIST and ACHIEVE trials, in which spironolactone was not superior to placebo in improving cardiovascular outcomes in patients with kidney failure. The incidence of moderate hyperkalemia in these trials was higher with spironolactone than with placebo.