Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients: A Randomized Placebo-Controlled Clinical Trial

Line A Mortensen, Bente Jespersen, Anne Sophie L Helligsoe, Birgitte Tougaard, Donata Cibulskyte-Ninkovic, Martin Egfjord, Lene Boesby, Niels Marcussen, Kirsten Madsen, Boye L Jensen, Inge Petersen, Claus Bistrup, Helle C Thiesson*

*Corresponding author for this work

Abstract

BACKGROUND: Long-term kidney allograft survival is hampered by progressive interstitial fibrosis and tubular atrophy. The SPIREN trial tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone stabilizes kidney function and attenuates glomerular barrier injury in kidney transplant patients treated with calcineurin inhibitors.

METHODS: Randomized, placebo-controlled, double blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for three years. Glomerular filtration rate was measured along with proteinuria and kidney fibrosis. The primary endpoint was change in measured glomerular filtration rate. Secondary outcomes were 24h proteinuria, kidney allograft fibrosis and cardiovascular events. Measured glomerular filtration rates, 24h proteinuria and blood pressure were determined yearly. Kidney biopsies were collected at baseline and after two years (n=48). Fibrosis was evaluated by quantitative stereology and classified according to Banff.

RESULTS: The groups were comparable at baseline except for slightly older allografts in the spironolactone group. Spironolactone reduced measured glomerular filtration rates (up to -7.6 (95% CI -10.9;-4.3) ml/min compared to placebo) independently of time since transplantation and blood pressure with no impact on the kidney function curve over time and reduced 24h proteinuria after one year. There was no significant effect of spironolactone on the development of interstitial fibrosis.

CONCLUSION: Spironolactone added to standard therapy for three years in kidney transplant patients did not improve kidney function, long-term proteinuria or interstitial fibrosis.

Original languageEnglish
JournalClinical journal of the American Society of Nephrology : CJASN
ISSN1555-9041
DOIs
Publication statusE-pub ahead of print - 27 Feb 2024

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