title: Randomized trial of immunosuppressive regimens in renal transplantation.
abstract: The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P ≤ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Miami Miller School of Medicine, P.O. Box 012440 (R-440), Miami, FL 33101, USA. gguerra@med.miami.edu
authors.forename: Giselle
authors.initials: G
authors.lastname: Guerra
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ciancio
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gaynor
authors.forename: Alberto
authors.initials: A
authors.lastname: Zarak
authors.forename: Randolph
authors.initials: R
authors.lastname: Brown
authors.forename: Lois
authors.initials: L
authors.lastname: Hanson
authors.forename: Junichiro
authors.initials: J
authors.lastname: Sageshima
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.forename: Warren
authors.initials: W
authors.lastname: Kupin
authors.forename: Lissett
authors.initials: L
authors.lastname: Tueros
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Alan S
authors.initials: AS
authors.lastname: Livingstone
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D003920:Diabetes Mellitus / Q000453:epidemiology; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D005431:Florida / Q000453:epidemiology; D006084:Graft Rejection / Q000517:prevention & control*; D019983:Guideline Adherence; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007239:Infections / Q000453:epidemiology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus