TY - JOUR

T1 - The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity

T2 - a multicenter randomized, double-blind, clinical trial (the SPIREN trial)

AU - Mortensen, Line Aas

AU - Thiesson, Helle C

AU - Tougaard, Birgitte

AU - Egfjord, Martin

AU - Fischer, Anne Sophie Lind

AU - Bistrup, Claus

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Calcineurin inhibitor induced nephrotoxicity contributes to late allograft failure in kidney transplant patients. Evidence points towards aldosterone to play a role in the development of fibrosis in multiple organs. Animal studies have indicated a beneficial effect of mineralocorticoid receptor antagonists preventing calcineurin inhibitor induced nephrotoxicity. Only few studies have explored this effect in humans. The objective of this study is to evaluate the effect of spironolactone on glomerular filtration rate and fibrosis in kidney transplant patients.METHOD: Prospective, double-blind, randomized, clinical trial including 170 prevalent kidney transplant patients. Patients are randomized to spironolactone 25-50 mg/day or placebo for three years. Primary outcome is glomerular filtration rate evaluated by chrome-EDTA clearance. Secondary outcomes are 24-h protein excretion, amount of interstitial fibrosis in renal allograft biopsies, and cardiovascular events. As an exploratory outcome, we aim to identify markers of fibrosis in blood and urine.DISCUSSION: Long term allograft survival remains a key issue in renal transplantation, partly due to calcineurin inhibitor induced nephrotoxicity. Evidence from animal- and small human studies indicate a beneficial effect of mineralocorticoid receptor antagonism on renal function and fibrosis. This study aims to test this hypothesis in a sufficiently powered randomized clinical trial. Results might influence the future management of long term allograft survival in renal transplantation.TRIAL REGISTRATION: ClinicalTrials.gov identifier (05/17/2012): NCT01602861 . EudraCT number (05/31/2011): 2011-002243-98.

AB - BACKGROUND: Calcineurin inhibitor induced nephrotoxicity contributes to late allograft failure in kidney transplant patients. Evidence points towards aldosterone to play a role in the development of fibrosis in multiple organs. Animal studies have indicated a beneficial effect of mineralocorticoid receptor antagonists preventing calcineurin inhibitor induced nephrotoxicity. Only few studies have explored this effect in humans. The objective of this study is to evaluate the effect of spironolactone on glomerular filtration rate and fibrosis in kidney transplant patients.METHOD: Prospective, double-blind, randomized, clinical trial including 170 prevalent kidney transplant patients. Patients are randomized to spironolactone 25-50 mg/day or placebo for three years. Primary outcome is glomerular filtration rate evaluated by chrome-EDTA clearance. Secondary outcomes are 24-h protein excretion, amount of interstitial fibrosis in renal allograft biopsies, and cardiovascular events. As an exploratory outcome, we aim to identify markers of fibrosis in blood and urine.DISCUSSION: Long term allograft survival remains a key issue in renal transplantation, partly due to calcineurin inhibitor induced nephrotoxicity. Evidence from animal- and small human studies indicate a beneficial effect of mineralocorticoid receptor antagonism on renal function and fibrosis. This study aims to test this hypothesis in a sufficiently powered randomized clinical trial. Results might influence the future management of long term allograft survival in renal transplantation.TRIAL REGISTRATION: ClinicalTrials.gov identifier (05/17/2012): NCT01602861 . EudraCT number (05/31/2011): 2011-002243-98.

KW - Calcineurin Inhibitors/adverse effects

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Glomerular Filtration Rate/drug effects

KW - Graft Survival/drug effects

KW - Humans

KW - Kidney/drug effects

KW - Kidney Transplantation/adverse effects

KW - Mineralocorticoid Receptor Antagonists/administration & dosage

KW - Prospective Studies

KW - Spironolactone/administration & dosage

KW - Treatment Outcome

U2 - 10.1186/s12882-018-0885-6

DO - 10.1186/s12882-018-0885-6

M3 - Journal article

C2 - 29724188

VL - 19

SP - 1

EP - 7

JO - BMC Nephrology

JF - BMC Nephrology

SN - 1471-2369

IS - 1

M1 - 105

ER -