title: Long-term kidney allograft function and survival in prednisone-free regimens: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.
abstract: OBJECTIVE
  The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.
  
  
  METHODS
  This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.
  
  
  RESULTS
  The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m(2), P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.
  
  
  CONCLUSIONS
  This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.
authors.affiliation: Kidney Transplant, Advocate Christ Medical Center, Oak Lawn, Illinois, USA.
authors.forename: Darshika
authors.initials: D
authors.lastname: Chhabra
authors.forename: Anton I
authors.initials: AI
authors.lastname: Skaro
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Leventhal
authors.forename: Pranav
authors.initials: P
authors.lastname: Dalal
authors.forename: Gaurav
authors.initials: G
authors.lastname: Shah
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gallon
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D016009:Chi-Square Distribution; D002641:Chicago; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus