Minimization of immunosuppressive therapy after renal transplantation: results of a randomized controlled trial

Am J Transplant. 2005 Jan;5(1):87-95. doi: 10.1111/j.1600-6143.2004.00638.x.


Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications. The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol (18.9 mg/dL [0.49 mmol/L]) and LDL-cholesterol (8.1 mg/dL [0.21 mmol/L]) between months 4 and 6 were greater in the steroid stop group (p < 0.001). Leukopenia (p = 0.0082), serious CMV infection (p = 0.024), anemia (p = NS) and diarrhea (p = NS) were less frequent in the MMF stop group. In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / pharmacology
  • Adult
  • Aged
  • Biopsy
  • Cardiovascular System
  • Child
  • Child, Preschool
  • Cholesterol / metabolism
  • Drug Therapy, Combination
  • Female
  • Graft Rejection
  • Graft Survival
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / metabolism
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Prospective Studies
  • Random Allocation
  • Risk
  • Tacrolimus / pharmacology
  • Time Factors


  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Cholesterol
  • Mycophenolic Acid
  • Tacrolimus