title: Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses.
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).
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: H
authors.initials: H
authors.lastname: Tedesco-Silva
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Felipe
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Ferreira
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Cristelli
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: N
authors.initials: N
authors.lastname: Oliveira
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Sandes-Freitas
authors.affiliation: Urology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: W
authors.initials: W
authors.lastname: Aguiar
authors.affiliation: Department of Immunogenetic, AFIP São Paulo, São Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Campos
authors.affiliation: Department of Immunogenetic, AFIP São Paulo, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Gerbase-DeLima
authors.affiliation: Department of Pathology, UNIFESP, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Franco
authors.affiliation: Nephrology Division, Hospital do Rim - UNIFESP, São Paulo, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Medina-Pestana
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D000068338:Everolimus; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus
keywords: Immune modulation; immunosuppression; kidney transplantation; nephrology