title: Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.
abstract: BACKGROUND
  To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection.
  
  
  METHODS
  A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids.
  
  
  RESULTS
  At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment.
  
  
  CONCLUSIONS
  The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.
authors.affiliation: Queen Elizabeth Hospital, Birmingham, England.
authors.forename: A D
authors.initials: AD
authors.lastname: Mayer
authors.forename: J
authors.initials: J
authors.lastname: Dmitrewski
authors.forename: J P
authors.initials: JP
authors.lastname: Squifflet
authors.forename: T
authors.initials: T
authors.lastname: Besse
authors.forename: B
authors.initials: B
authors.lastname: Grabensee
authors.forename: B
authors.initials: B
authors.lastname: Klein
authors.forename: F W
authors.initials: FW
authors.lastname: Eigler
authors.forename: U
authors.initials: U
authors.lastname: Heemann
authors.forename: R
authors.initials: R
authors.lastname: Pichlmayr
authors.forename: M
authors.initials: M
authors.lastname: Behrend
authors.forename: Y
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: J
authors.initials: J
authors.lastname: Donck
authors.forename: J
authors.initials: J
authors.lastname: van Hooff
authors.forename: M
authors.initials: M
authors.lastname: Christiaans
authors.forename: J M
authors.initials: JM
authors.lastname: Morales
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.forename: R W
authors.initials: RW
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Short
authors.forename: B
authors.initials: B
authors.lastname: Buchholz
authors.forename: N
authors.initials: N
authors.lastname: Rehmert
authors.forename: W
authors.initials: W
authors.lastname: Land
authors.forename: S
authors.initials: S
authors.lastname: Schleibner
authors.forename: J L
authors.initials: JL
authors.lastname: Forsythe
authors.forename: D
authors.initials: D
authors.lastname: Talbot
authors.forename: E
authors.initials: E
authors.lastname: Pohanka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus