Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

• Miguel Gómez-Bravo ^[1] ; Martín Prieto Castillo ^[13] ; Miquel Navasa ^[2] ; Gloria Sánchez-Antolín ^[3] ; Laura Lladó ^[4] ; Alejandra Otero ^[14] ; Trinidad Serrano ^[5] ; Carlos Jiménez Romero ^[6] ; Miguel García González ^[7] ; Andrés Valdivieso ^[15] ; María Luisa González-Diéguez ^[8] ; Manuel de la Mata ^[16] ; José A. Pons ^[9] ; Magdalena Salcedo ^[10] ; Juan M. Rodrigo ^[17] ; Valentín Cuervas-Mons ^[11] ; Antonio González Rodríguez ^[18] ; Mireia Caralt ^[19] ; Fernando Pardo ^[12] ; Evaristo Varo Pérez ^[20] ; Gonzalo Crespo ^[2] ; Ángel Rubin ^[13] ; Magda Guilera ^[21] ; Anna Aldea ^[21] ; Julio Santoyo ^[17]
  1. [1] Hospital Universitario Virgen del Rocío

     Hospital Universitario Virgen del Rocío

     Sevilla, España

     
  2. [2] Universitat de Barcelona

     Universitat de Barcelona

     Barcelona, España

     
  3. [3] Hospital Universitario Pío del Río Hortega

     Hospital Universitario Pío del Río Hortega

     Valladolid, España

     
  4. [4] Hospital Universitari de Bellvitge

     Hospital Universitari de Bellvitge

     l'Hospitalet de Llobregat, España

     
  5. [5] Hospital Clínico Universitario Lozano Blesa

     Hospital Clínico Universitario Lozano Blesa

     Zaragoza, España

     
  6. [6] Hospital Universitario 12 de Octubre

     Hospital Universitario 12 de Octubre

     Madrid, España

     
  7. [7] Hospital Ramón y Cajal

     Hospital Ramón y Cajal

     Madrid, España

     
  8. [8] Hospital Universitario Central de Asturias

     Hospital Universitario Central de Asturias

     Oviedo, España

     
  9. [9] Hospital Virgen de la Arrixaca

     Hospital Virgen de la Arrixaca

     Murcia, España

     
  10. [10] Hospital General Universitario Gregorio Marañón

      Hospital General Universitario Gregorio Marañón

      Madrid, España

      
  11. [11] Hospital Universitario Puerta de Hierro

      Hospital Universitario Puerta de Hierro

      Madrid, España

      
  12. [12] Clínica Universitaria de Navarra

      Clínica Universitaria de Navarra

      Pamplona, España

      
  13. [13] Hospital Universitari I Politècnic La Fe-IIS La Fe. Valencia, Spain
  14. [14] Hospital Universitario de A Coruña. A Coruña, Spain
  15. [15] Hospital Universitario Cruces. Bilbao, Spain.
  16. [16] HU Reina Sofía. CIBERehd, IMIBIC. Córdoba, Spain
  17. [17] Hospital Regional Universitario. Málaga, Spain.
  18. [18] Hospital Universitario Ntra. Sra. de Candelaria. Tenerife, Spain.
  19. [19] Hospital Valle de Hebrón. Universidad Autónoma de Barcelona. Barcelona, Spain
  20. [20] Hospital Clínico Universitario de Santiago de Compostela. Santiago de Compostela, A Coruña. Spain.
  21. [21] Novartis Farmacéutica S.A. Barcelona, Spain

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• Localización: Revista Española de Enfermedades Digestivas, ISSN-e 2340-4167, ISSN 1130-0108, Vol. 114, Nº. 6, 2022, págs. 335-342
• Idioma: inglés
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• Resumen

  • 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.