Resumen de Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study
Miguel Ángel Gómez Bravo, Martín Prieto Castillo, Miguel Navasa Anadón, Gloria Sánchez Antolín, Laura Lladó Garriga, Alejandra Otero Ferreiro, M. Trinidad Serrano Aulló, Luis Carlos Jiménez Romero, Miguel A. Garcia Gonzalez, Andrés Valdivieso López, M. Luisa González Diéguez, Manuel de la Mata Herrera, José Antonio Pons Miñano, Magdalena Salcedo Plaza, Juan Miguel Rodrigo López, Valentín Cuervas Mons Martínez, Antonio González Rodríguez, Mireia Caralt Barba, Fernando Pardo Sánchez, Evaristo Varo Pérez, Gonzalo Crespo Conde, Ángel Rubín Suárez, Magda Guilera Sardà, Anna Aldea Parés, Julio Santoyo Santoyo
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.
