title: Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients.
abstract: BACKGROUND
  Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients.
  
  
  METHODS
  Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months.
  
  
  RESULTS
  At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05).
  
  
  CONCLUSIONS
  Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.
authors.affiliation: Université Catholique de Louvain, Cliniques Universitaires Saint Luc, 10 Ave Hippocrate, B-1200 Brussels, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Squifflet
authors.forename: L
authors.initials: L
authors.lastname: Bäckman
authors.forename: K
authors.initials: K
authors.lastname: Claesson
authors.forename: K H
authors.initials: KH
authors.lastname: Dietl
authors.forename: H
authors.initials: H
authors.lastname: Ekberg
authors.forename: J L
authors.initials: JL
authors.lastname: Forsythe
authors.forename: U
authors.initials: U
authors.lastname: Kunzendorf
authors.forename: U
authors.initials: U
authors.lastname: Heemann
authors.forename: W
authors.initials: W
authors.lastname: Land
authors.forename: J M
authors.initials: JM
authors.lastname: Morales
authors.forename: F
authors.initials: F
authors.lastname: Mühlbacher
authors.forename: D
authors.initials: D
authors.lastname: Talbot
authors.forename: D
authors.initials: D
authors.lastname: Taube
authors.forename: G
authors.initials: G
authors.lastname: Tyden
authors.forename: J
authors.initials: J
authors.lastname: van Hooff
authors.forename: S
authors.initials: S
authors.lastname: Schleibner
authors.forename: Y
authors.initials: Y
authors.lastname: Vanrenterghem
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D002102:Cadaver; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus