Year 2022 / Volume 114 / Number 6
Original
Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

335-342

DOI: 10.17235/reed.2022.8549/2021

Miguel Gómez-Bravo, Martín Prieto Castillo, Miquel Navasa, Gloria Sánchez-Antolín, Laura Lladó, Alejandra Otero, Trinidad Serrano, Carlos Jiménez Romero, Miguel García González, Andrés Valdivieso, María Luisa González-Diéguez, Manuel de la Mata, José A. Pons, Magdalena Salcedo, Juan M. Rodrigo, Valentín Cuervas-Mons, Antonio González Rodríguez, Mireia Caralt, Fernando Pardo, Evaristo Varo Pérez, Gonzalo Crespo, Ángel Rubin, Magda Guilera, Anna Aldea, Julio Santoyo,

Abstract
Background and Aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.
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References
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Gómez-Bravo M, Prieto Castillo M, Navasa M, Sánchez-Antolín G, Lladó L, Otero A, et all. Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study. 8549/2021


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Publication history

Received: 23/12/2021

Accepted: 05/04/2022

Online First: 26/04/2022

Published: 07/06/2022

Article revision time: 97 days

Article Online First time: 124 days

Article editing time: 166 days


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