Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial.
The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy. The primary safety endpoints were hyperkalemia (potassium > 6.5 mEq/L) and hypotension requiring emergency department visit or hospitalization. Diastolic function was assessed by Doppler echocardiography. 125 participants (97%) completed dose escalation, with no significant difference in permanent study drug discontinuation between the groups (27.5% in placebo versus 16.7% in the combined spironolactone groups and 28% in the 50 mg group). Hyperkalemia frequency was similar between spironolactone and placebo (0.49 versus 0.50 events per patient-year) but demonstrated a significant linear trend due primarily to an increased event rate at the 50 mg dose (0.89 events per patient-year). The primary hypotension outcome was infrequent and similar with spironolactone and placebo (0.11 versus 0 events per patient-year). Gynecomastia was rare and did not differ significantly between groups. Change in diastolic function was similar with spironolactone and placebo. Spironolactone appears safe in carefully monitored maintenance hemodialysis patients, but did not affect cardiovascular parameters in this small study. Hyperkalemia occurs more frequently as dosage increases to 50 mg daily.
['Charytan|David M|DM|', 'Himmelfarb|Jonathan|J|', 'Ikizler|T Alp|TA|', 'Raj|Dominic S|DS|', 'Hsu|Jesse Y|JY|', 'Landis|J Richard|JR|', 'Anderson|Amanda H|AH|', 'Hung|Adriana M|AM|', 'Mehrotra|Rajnish|R|', 'Sharma|Shailendra|S|', 'Weiner|Daniel E|DE|', 'Williams|Mark|M|', 'DiCarli|Marcelo|M|', 'Skali|Hicham|H|', 'Kimmel|Paul L|PL|', 'Kliger|Alan S|AS|', 'Dember|Laura M|LM|', '|||']
D000328:Adult D000368:Aged D000450:Aldosterone D002318:Cardiovascular Diseases D003971:Diastole D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D015150:Echocardiography, Doppler D005240:Feasibility Studies D005260:Female D006177:Gynecomastia D006801:Humans D006947:Hyperkalemia D007022:Hypotension D007676:Kidney Failure, Chronic D008297:Male D008875:Middle Aged D000451:Mineralocorticoid Receptor Antagonists D010919:Placebos D011188:Potassium D006435:Renal Dialysis D013148:Spironolactone
multiple dosage hemodialysis mineralocorticoid blockade randomized controlled trial