Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients (the SPIREN trial)

作者：Line Aas Mortensen, Bente Jespersen, Anne Sophie Lind Helligsoe, Birgitte Tougaard, Donata Cibulskyte-Ninkovic, Martin Egfjord, Lene Boesby, Niels Marcussen, Kirsten Madsen, Boye L. Jensen, Inge Petersen, Claus Bistrup, Helle C. Thiesson · 发表于：Clinical Journal of the American Society of Nephrology · 年份：2024 · DOI：10.2215/cjn.0000000000000439 · 被引用次数：29 · 研究领域：Electrolyte and hormonal disorders、Potassium and Related Disorders、Liver Disease and Transplantation

Key Points Spironolactone is safe for kidney transplant patients. Spironolactone reduces kidney function by an acute effect, whereafter it remains stable. Spironolactone does not affect the progression of interstitial fibrosis in protocol biopsies. 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 We conducted a randomized, placebo-controlled, double-blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for 3 years. GFR was measured along with proteinuria and kidney fibrosis. The primary end point was change in measured GFR. Secondary outcomes were 24-hour proteinuria, kidney allograft fibrosis, and cardiovascular events. Measured GFRs, 24-hour proteinuria, and BP were determined yearly. Kidney biopsies were collected at baseline and after 2 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 GFRs (up to –7.6 [95% confidence interval, −10.9 to −4.3] ml/min compared with placebo) independently of time since tr...