title: Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa).
abstract: 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].
authors.affiliation: Division of Cardiology, Department of Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Hammer
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Christoph
authors.initials: C
authors.lastname: Röser
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hofmann
authors.forename: Nils
authors.initials: N
authors.lastname: Pollak
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D011446:Prospective Studies; D006435:Renal Dialysis; D013148:Spironolactone / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: aldosterone; dialysis; end stage renal disease; left ventricular hypertrophy; mineralocorticoid receptor antagonist; spironolactone