title: Secondary effects of immunosuppressive drugs after simultaneous pancreas-kidney transplantation.
abstract: BACKGROUND
  This report examines the early and late secondary effects of tacrolimus, cyclosporin microemulsion (ME), mycophenolate mofetil (MMF) and rabbit anti-thymocyte globulin (rATG) in simultaneous pancreas-kidney (SPK) recipients.
  
  
  METHODS
  Of the 205 patients participating in the Euro-SPK 001 study, 103 were randomized to tacrolimus (0.2 mg/kg) and 102 to cyclosporin-ME (7 mg/kg). All patients received rATG for 4 days [ATG-Fresenius (ATG-F) 4 mg/kg/day or Thymoglobulin (Thymo-S) 1.25 mg/kg/day] plus MMF and short-term corticosteroids.
  
  
  RESULTS
  Thymo-S induction therapy was associated with a lower white cell count in the first 3 months than was seen with ATG-F, while ATG-F caused a lower initial nadir in platelet count. Both polyclonal preparations were well tolerated and no clinically relevant differences were observed with respect to side effects such as infections and malignancies. High cyclosporin-ME trough levels were associated with pancreas graft thrombosis, and concentrations >150 ng/ml were associated with poor renal allograft function. Treatment discontinuation was higher with cyclosporin-ME (57.8%) than with tacrolimus-based therapy (36.9%) due to more frequent toxicity, graft loss and lack of efficacy requiring a switch to tacrolimus. The main reason for withdrawal in the tacrolimus group was MMF discontinuation; MMF-related side effects resulted in more frequent dose reductions to <2 g/day and discontinuations in the tacrolimus group, and indirectly indicate a higher dose-corrected exposure to mycophenolic acid, as previously observed in kidney transplant patients.
  
  
  CONCLUSIONS
  Short-term induction therapy is effective and well tolerated in patients undergoing SPK transplantation. Tacrolimus was the preferred immunosuppressive agent, resulting in fewer cases of pancreas graft loss and drug discontinuation compared with cyclosporin-ME.
authors.affiliation: Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium.
authors.forename: Dirk R J
authors.initials: DR
authors.lastname: Kuypers
authors.forename: Jacques
authors.initials: J
authors.lastname: Malaise
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.forename: Bart
authors.initials: B
authors.lastname: Maes
authors.forename: Willy
authors.initials: W
authors.lastname: Coosemans
authors.forename: Jacques
authors.initials: J
authors.lastname: Pirenne
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
mesh_terms: D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000601:surgery; D003928:Diabetic Nephropathies / Q000150:complications / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation; D007958:Leukocyte Count; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016035:Pancreas Transplantation; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus