title: Minimization of immunosuppressive therapy after renal transplantation: results of a randomized controlled trial.
abstract: 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.
authors.affiliation: Department of Nephrology, University Hospital Gasthuisberg, Leuven, Belgium. yves.vanrenterghem@uz.kuleuven.ac.be
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van Hooff
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Squifflet
authors.forename: Kaija
authors.initials: K
authors.lastname: Salmela
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Rahul M
authors.initials: RM
authors.lastname: Jindal
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
authors.forename: Luis Sanchez
authors.initials: LS
authors.lastname: Sicilia
authors.forename: John N
authors.initials: JN
authors.lastname: Boletis
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyo
authors.forename: Manuel Arias
authors.initials: MA
authors.lastname: Rodriguez
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001706:Biopsy; D002319:Cardiovascular System; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D012306:Risk; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D002784:Cholesterol; D009173:Mycophenolic Acid; D016559:Tacrolimus