A randomized, double-blind, placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients.
OBJECTIVE
Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium.


METHODS
HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years.


RESULTS
Fifty-three age- and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 +/- 0.07, spironolactone: 0.01 +/- 0.04; carotid bifurcation, placebo: 0.15 +/- 0.27, spironolactone: 0.0001 +/- 0.01; internal carotid, placebo: 0.10 +/- 0.12, spironolactone: -0.10 +/- 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group.


CONCLUSIONS
Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients.
Faculty of Medicine, Universidad Los Andes, Santiago, Chile.
Antonio
A
Vukusich
Sonia
S
Kunstmann
Cristian
C
Varela
Daniela
D
Gainza
Sebastian
S
Bravo
Daniela
D
Sepulveda
Gabriel
G
Cavada
Luis
L
Michea
Elisa T
ET
Marusic
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects*; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002677:Chile; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D015990:Placebo Effect; D011188:Potassium / Q000097:blood; D006435:Renal Dialysis; D013148:Spironolactone / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects*; D014463:Ultrasonography
D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D011188:Potassium