Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses

Am J Transplant. 2015 Oct;15(10):2655-64. doi: 10.1111/ajt.13327. Epub 2015 May 18.

Abstract

This study compared the incidence of CMV infection/disease in de novo kidney transplant recipients receiving everolimus or mycophenolate and no CMV pharmacological prophylaxis. We randomized 288 patients to receive a single 3 mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r-ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n = 101). The primary end-point was the incidence of first CMV infection/disease in the intention-to-treat population at 12 months. Patients treated with r-ATG/EVR showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037-0.29; p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13-0.48; p < 0.001) in the incidence of CMV infection/disease compared to BAS/MPS. There were no differences in the incidence of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound-healing complications, delayed graft function, and proteinuria. Mean estimated glomerular filtration rate was lower in BAS/EVR (65.7 ± 21.8 vs. 60.6 ± 20.9 vs. 69.5 ± 21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no pharmacological CMV prophylaxis, reduced-dose tacrolimus and everolimus was associated with a significant reduction in the incidence of CMV infection/disease compared to standard tacrolimus dose and mycophenolate (ClinicalTrials.gov NCT01354301).

Keywords: Immune modulation; immunosuppression; kidney transplantation; nephrology.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antilymphocyte Serum / therapeutic use
  • Basiliximab
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Everolimus / administration & dosage*
  • Everolimus / therapeutic use
  • Female
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Postoperative Complications / epidemiology
  • Postoperative Complications / immunology
  • Postoperative Complications / prevention & control*
  • Prednisone / therapeutic use
  • Prospective Studies
  • Recombinant Fusion Proteins / therapeutic use
  • Sirolimus / therapeutic use
  • Tacrolimus / administration & dosage*
  • Tacrolimus / therapeutic use
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • Basiliximab
  • Everolimus
  • Mycophenolic Acid
  • Prednisone
  • Sirolimus
  • Tacrolimus

Associated data

  • ClinicalTrials.gov/NCT01354301