title: Sirolimus in combination with tacrolimus is associated with worse renal allograft survival compared to mycophenolate mofetil combined with tacrolimus.
abstract: Cyclosporine (CsA) nephrotoxicity is enhanced by sirolimus (SRL). Tacrolimus is perceived to be less nephrotoxic than CsA, and therefore, CsA has been largely replaced by tacrolimus (TAC) when calcineurin inhibitors are used with SRL. We analyzed 44 915 adult renal transplants in the Scientific Renal Transplant Registry (SRTR) from 2000 to 2004. Three thousand five hundred twenty-four (7.8%) patients received a baseline immunosuppressive regimen of TAC/SRL, with an inferior overall (log-rank p<0.001) and death-censored graft survival (p<0.001) as compared to TAC/MMF (N=27 007). This effect was confirmed in multivariate Cox models; the adjusted hazard ratio (AHR) for overall graft loss with TAC/SRL was 1.47 (95% CI=1.32, 1.63) and for CsA/SRL 1.38 (95% CI=1.20, 1.59) relative to TAC/MMF. These effects were most apparent in high-risk transplants. Six-month acute rejection rates were low (11.5-12.6%) and not different between groups. In summary, national data indicate that TAC/SRL as compared to TAC/MMF is associated with significantly worse renal allograft survival in all subgroups of patients and, in particular, higher-risk transplants. These results have to be interpreted in the context of the inherent limitations of any retrospective database analysis and evaluated in context with data from prospective clinical trials.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Florida, USA. meierhu@medicine.ufl.edu
authors.forename: Herwig-Ulf
authors.initials: HU
authors.lastname: Meier-Kriesche
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Schold
authors.forename: Titte R
authors.initials: TR
authors.lastname: Srinivas
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Howard
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Bruce
authors.initials: B
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002102:Cadaver; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D019992:Databases as Topic; D004359:Drug Therapy, Combination; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus