title: A prospective, randomized trial to compare tacrolimus and prednisone with and without mycophenolate mofetil in patients undergoing renal transplantation: first report.
abstract: OBJECTIVE
  Between September 20, 1995 and September 20, 1996, 120 patients were entered into a prospective, randomized trial comparing tacrolimus and prednisone with (61) and without (59) 2 gm. mycophenolate mofetil daily to determine whether mycophenolate mofetil was associated with a lower incidence of rejection.
  
  
  METHODS
  Mean recipient age plus or minus standard deviation was 50.8+/-14.1 years (range 18.8 to 84.1). Mean donor age was 34.3+/-21.7 years (range 0.01 to 76). Of the donors 18 (15%) were older than 60 years. Mean cold ischemia time was 30.9+/-8.4 hours (range 14.2 to 49). Median followup was 8.6+/-0.5 months.
  
  
  RESULTS
  The 6-month actuarial patient survival was 95%, 92% in the double therapy group and 98% in the triple therapy group (not significant). The 6-month actuarial graft survival was 88%, 84% in the double therapy group and 92% in the triple therapy group (not significant). The overall incidence of rejection and steroid resistant rejection was 34.2 and 4.2%, respectively. There was a strong trend toward less rejection in the mycophenolate mofetil group than in the double therapy group (26.2 versus 42.4%). Crossover was common, and was 42.6% from triple to double therapy and 18.6% from double to triple therapy. The reasons for discontinuation of mycophenolate mofetil were gastrointestinal toxicity, primarily diarrhea, or less commonly hematological toxicity, primarily neutropenia or thrombocytopenia. Gastrointestinal toxicity was ameliorated by separating the doses of tacrolimus and mycophenolate mofetil by 2 to 4 hours, and reducing the dose to 1 gm. daily.
  
  
  CONCLUSIONS
  Mycophenolate mofetil appears to be a useful third agent with tacrolimus in patients undergoing renal transplantation, and is associated with a reduction in the rate of rejection and a low incidence of steroid resistant rejection. There is a high incidence of gastrointestinal toxicity associated with the 2 gm. daily dose but this complication is relatively straightforward to manage.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: M L
authors.initials: ML
authors.lastname: Jordan
authors.forename: V P
authors.initials: VP
authors.lastname: Scantlebury
authors.forename: C
authors.initials: C
authors.lastname: Vivas
authors.forename: H A
authors.initials: HA
authors.lastname: Gritsch
authors.forename: F A
authors.initials: FA
authors.lastname: Casavilla
authors.forename: J
authors.initials: J
authors.lastname: McCauley
authors.forename: J R
authors.initials: JR
authors.lastname: Johnston
authors.forename: P
authors.initials: P
authors.lastname: Randhawa
authors.forename: W
authors.initials: W
authors.lastname: Irish
authors.forename: T R
authors.initials: TR
authors.lastname: Hakala
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
authors.forename: T E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D016030:Kidney Transplantation / Q000401:mortality; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011241:Prednisone / Q000008:administration & dosage*; D011446:Prospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus