Mineralocorticoid Receptor Blockade Reduced Oxidative Stress in Renal Transplant Recipients: A Double-Blind, Randomized Pilot Study

Abstract

Background: Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes. This study was designed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors. Methods: 20 adult kidney transplant recipients from living donors were included in a double-blind, randomized, placebo-controlled clinical pilot study that compared spironolactone and placebo. Placebo or spironolactone (25 mg) was administered 1 day before and 3 days posttransplantation. Renal function and urinary kidney injury molecule-1, interleukin-18, and heat shock protein 72 as well as urinary hydrogen peroxide (H₂O₂) levels were quantified. Results: No significant differences were seen between the groups studied regarding age, gender, indication for kidney transplantation, residual renal function, renal replacement therapy, or warm and cold ischemia periods. In contrast, spironolactone administration significantly reduced the oxidative stress assessed by the urinary H₂O₂ excretion, in spite of no differences in renal function or reduction in tubular injury biomarkers. Conclusions: The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H₂O₂ as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.