Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa).

BACKGROUND: End-stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality secondary to cardiac and vascular causes, particularly sudden cardiac death (SCD). Left ventricular (LV) hypertrophy is a frequent finding and constitutes an independent predictor of mortality risk in these patients. Mineralocorticoid receptor antagonists (MRAs) are cardioprotective in heart failure patients and effectively reduce LV mass, but are considered inappropriate in patients with severe renal impairment, given their potential to cause hyperkalaemia. Recent data from small clinical studies suggest that MRAs may be safe in patients undergoing regular haemodialysis, but cardiovascular (CV) protection in these patients is unclear. We here review the literature on CV effects of MRA in dialysis patients and report the design of the Mineralocorticoid Receptor antagonists in End-stage renal Disease (MiREnDa) trial. METHODS: The MiREnDa trial is a prospective randomized, placebo-controlled, double-blind, parallel group, multi-centre, intervention study investigating the effects of spironolactone (50 mg daily) compared with placebo in maintenance haemodialysis patients. The change in LV mass index (LVMI) as assessed by cardiac magnet resonance imaging (CMR) constitutes the primary efficacy end point. Secondary end points include changes in LV geometry and function, office and 24-h ambulatory blood pressure, cardiac arrhythmias, vascular function parameters, measures of heart failure and quality of life. Pre-dialysis potassium levels and the incidence of threatening hyperkalaemia (pre-dialysis potassium ≥6.5 mmol/L) constitute safety end points. CONCLUSIONS: MiREnDa will investigate CV efficacy and safety of spironolactone in haemodialysis patients [clinical trials.gov NCT01691053].