title: Tacrolimus/sirolimus versus tacrolimus/mycophenolate in kidney transplantation: improved 3-year graft and patient survival in recent era.
abstract: BACKGROUND
  Registry analyses suggest that tacrolimus (TAC)/mycophenolate (MPA) immunosuppression is associated with superior kidney graft survival versus TAC/sirolimus (SRL). Large single-center experience can assist in clarifying these findings, by examining outcomes related to specific utilization practice.
  
  
  METHODS
  We retrospectively examined the outcomes of 518 consecutive first renal transplants at a single center treated with TAC/SRL (n=307) or TAC/MPA (n=211) with prednisone. Graft and patient survival, acute rejection, and 1-year glomerular filtration rate (GFR) were analyzed by era of transplant (2000-2002 vs. 2003-2006). Changes in TAC/SRL utilization between eras included elimination of the SRL loading dose and a reduction in TAC target trough concentrations.
  
  
  RESULTS
  Three-year graft survival with TAC/SRL was lower when first used (2000-2002) because of a higher incidence of patient death, primarily due to cardiovascular causes. Survival improved from 85.3% to 95.9% between 2000 to 2002 and 2003 to 2006 (P=0.001), with comparable graft and patient survival between TAC/SRL and TAC/MPA cohorts, confirmed following multivariable analysis controlling for donor and recipient factors. Rates of BK virus and acute rejection were comparable, but a higher incidence of hyperlipidemia, anemia, posttransplant diabetes, and a lower 1-year GFR (57.6 vs. 63.1 mL/min, P=0.008) was noted in the TAC/SRL cohort.
  
  
  CONCLUSIONS
  These data, as the largest long-term single-center report comparing TAC/SRL with TAC/MPA in kidney transplantation, demonstrate worse patient survival initially with TAC/SRL, with improved outcomes in a later era that were temporally associated with reduced TAC exposure. Differences in cardiovascular risk factors and 1-year GFR highlight the need for further investigation of the optimal utilization of SRL in kidney transplantation.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Gralla
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Wiseman
mesh_terms: D000328:Adult; D002102:Cadaver; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus