title: A comparative, randomized trial of concentration-controlled sirolimus combined with reduced-dose tacrolimus or standard-dose tacrolimus in renal allograft recipients.
abstract: BACKGROUND
  The clinical safety and efficacy of sirolimus plus reduced-dose tacrolimus was evaluated in de novo renal allograft recipients enrolled in a comparative, open-label study.
  
  
  METHODS
  One hundred twenty-eight renal allograft recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months. The primary efficacy endpoint was calculated creatinine clearance values at 6 months.
  
  
  RESULTS
  Demographic variables were similar between groups. At 6 months, mean (± standard deviation) calculated creatinine clearance was significantly improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum creatinine values were not significantly different. Patient survival (95.2% and 96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7% with sTAC (P = .095).
  
  
  CONCLUSIONS
  The rTAC regimen provided effective immunosuppression and was associated with improved creatinine clearance. Adequate immunosuppressant exposure must be achieved in the early postoperative period to minimize the risk of acute rejection.
authors: Ruhr-Universitat, Bochum, Germany. Wolf.Bechstein@kgu.de
authors: W O
authors: WO
authors: Bechstein
authors: L
authors: L
authors: Paczek
authors: L
authors: L
authors: Wramner
authors: J-P
authors: JP
authors: Squifflet
authors: A J
authors: AJ
authors: Zygmunt
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus; D016559:Tacrolimus