title: Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.
abstract: BACKGROUND
  Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.
  
  
  METHODS
  A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.
  
  
  RESULTS
  There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.
  
  
  CONCLUSIONS
  All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.
authors.affiliation: Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: N
authors.initials: N
authors.lastname: Ahsan
authors.forename: T
authors.initials: T
authors.lastname: Gonwa
authors.forename: P
authors.initials: P
authors.lastname: Halloran
authors.forename: M
authors.initials: M
authors.lastname: Stegall
authors.forename: M
authors.initials: M
authors.lastname: Hardy
authors.forename: R
authors.initials: R
authors.lastname: Metzger
authors.forename: C
authors.initials: C
authors.lastname: Shield
authors.forename: L
authors.initials: L
authors.lastname: Rocher
authors.forename: J
authors.initials: J
authors.lastname: Scandling
authors.forename: J
authors.initials: J
authors.lastname: Sorensen
authors.forename: L
authors.initials: L
authors.lastname: Mulloy
authors.forename: J
authors.initials: J
authors.lastname: Light
authors.forename: C
authors.initials: C
authors.lastname: Corwin
authors.forename: G
authors.initials: G
authors.lastname: Danovitch
authors.forename: M
authors.initials: M
authors.lastname: Wachs
authors.forename: P
authors.initials: P
authors.lastname: van Veldhuisen
authors.forename: K
authors.initials: K
authors.lastname: Salm
authors.forename: D
authors.initials: D
authors.lastname: Tolzman
authors.forename: W E
authors.initials: WE
authors.lastname: Fitzsimmons
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D002102:Cadaver; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; 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; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011182:Postoperative Care; D011446:Prospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus