EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial

BackgroundDespite advances in immunosuppressive therapy, kidney graft survival has failed to improve during the last decades. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological mechanisms underlying delayed graft function, which is associated with poor long-term graft survival. Due to organ shortage, the proportion of grafts from expanded criteria donors (ECDs) is ever growing. These grafts may particularly benefit from IRI prevention. In preclinical models, mineralocorticoid receptor antagonists (MRAs) have been shown to efficiently prevent IRI. This study aims to assess the effect of MRA administration in the early phase of kidney transplantation (KT) among recipients of ECD grafts on mid-term graft function.Methods/designThis is a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients on hemodialysis and undergoing a single or a dual KT from an ECD will be eligible for inclusion. We plan to randomize 132 patients. Included patients will be randomized (1:1) to receive either eplerenone 25mg every 12h during 4days (the first dose being administered just prior to KT) or placebo. The primary outcome is graft function at 3months, assessed by glomerular filtration rate (GFR, in mL/min/1.73m(2)) measured using iohexol clearance. Secondary outcomes include (1) proportion of patients with either dialysis dependency or a GFR<30mL/min/1.73m(2) at 3months, (2) proportion of patients with immediate, slow, or delayed graft function, (3) proteinuria at 3months, (4) occurrence of hyperkalemia during the first week following KT, (5) length of hospital stay for the KT, and (6) occurrence of biopsy-proven acute rejection in the first 3months following KT. Estimated GFR, graft, and patient survival will also be collected at 1, 3, and 10years via the national database of organ recipients.DiscussionImprovement of ECD grafts is a public health priority, since better ECD outcomes could eventually limit organ shortage. MRA administration in the early phase of KT may prevent IRI and subsequently improve mid-term graft function. The trial will also assess the safety of MRA administration in this population, primarily the absence of threatening hyperkalemia.Trial registrationClinicalTrials.gov, NCT02490904. Registered on 1 July 2015.