An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients

Braz J Med Biol Res. 2021 Mar 3;54(4):e9369. doi: 10.1590/1414-431X20209369. eCollection 2021.


Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Drug Therapy, Combination
  • Everolimus / therapeutic use
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Tacrolimus* / therapeutic use


  • Immunosuppressive Agents
  • Everolimus
  • Tacrolimus