The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity:A multicenter randomized, double-blind, clinical trial (the SPIREN trial)

Autor: Helle C. Thiesson, Line Aas Mortensen, Claus Bistrup, Birgitte Tougaard, Anne Sophie Lind Fischer, Martin Egfjord
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Nephrology
030232 urology & nephrology
Calcineurin Inhibitors/adverse effects
Spironolactone
030204 cardiovascular system & hematology
Kidney/drug effects
Kidney
lcsh:RC870-923
Graft Survival/drug effects
Glomerular Filtration Rate/drug effects
Kidney transplantation
Study Protocol
chemistry.chemical_compound
0302 clinical medicine
Mineralocorticoid receptor
Prospective Studies
Aldosterone
Mineralocorticoid Receptor Antagonists
Kidney Transplantation/adverse effects
Graft Survival
IFTA
Spironolactone/administration & dosage
Mineralocorticoid Receptor Antagonists/administration & dosage
Treatment Outcome
Mineralocorticoid
Drug Therapy
Combination
Glomerular filtration rate
medicine.medical_specialty
Calcineurin Inhibitors
Urology
Renal function
Tacrolimus
Nephrotoxicity
03 medical and health sciences
Cyclosporine A
Double-Blind Method
Internal medicine
medicine
Humans
business.industry
lcsh:Diseases of the genitourinary system. Urology
medicine.disease
Fibrosis
Calcineurin
Transplantation
chemistry
business
Zdroj: Mortensen, L A, Thiesson, H C, Tougaard, B, Egfjord, M, Fischer, A S L & Bistrup, C 2018, ' The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity : A multicenter randomized, double-blind, clinical trial (the SPIREN trial) ', BMC Nephrology, vol. 19, no. 1, 105 . https://doi.org/10.1186/s12882-018-0885-6
BMC Nephrology, Vol 19, Iss 1, Pp 1-7 (2018)
BMC Nephrology
Mortensen, L A, Thiesson, H C, Tougaard, B, Egfjord, M, Fischer, A S L & Bistrup, C 2018, ' The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity : a multicenter randomized, double-blind, clinical trial (the SPIREN trial) ', BMC Nephrology, vol. 19, no. 1, 105, pp. 1-7 . https://doi.org/10.1186/s12882-018-0885-6
ISSN: 0160-2861
DOI: 10.1186/s12882-018-0885-6
Popis: 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.
Databáze: OpenAIRE
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