Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients

PLoS One. 2015 Sep 25;10(9):e0135439. doi: 10.1371/journal.pone.0135439. eCollection 2015.

Abstract

Introduction: Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.

Patients/methods: We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.

Results: Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).

Conclusion: In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Biomarkers
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Therapy, Combination
  • Everolimus / administration & dosage
  • Everolimus / adverse effects
  • Female
  • Graft Rejection / drug therapy
  • Graft Rejection / immunology
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Hospitalization
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / immunology
  • Kidney Function Tests
  • Kidney Transplantation* / adverse effects
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Opportunistic Infections / etiology
  • Retrospective Studies
  • Tissue Donors
  • Transplant Recipients*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • HLA Antigens
  • Immunosuppressive Agents
  • Isoantibodies
  • Everolimus
  • Mycophenolic Acid

Grant support

This investigator-initiated trial was supported by an unrestricted grant from Novartis Germany, Nuremberg, Germany. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.