Long-term outcomes after cyclosporine or mycophenolate withdrawal in kidney transplantation - results from an aborted trial.
Long-term triple immunosuppressive therapy with cyclosporine (CsA), mycophenolate mofetil (MMF) and prednisolone may be excessively powerful for many transplant recipients. We compared withdrawal of either MMF or CsA in stable kidney transplants on triple immunosuppression. The study was a prospective, randomized, controlled 12-months trial in stable kidney transplants. The patients who withdrew CsA were given MMF 2 g/d, and CsA troughs were between 75 and 125 ng/mL in MMF withdrawal. Planned inclusion was 298 patients. The study was prematurely aborted after inclusion of 39 patients. Acute rejection rates were 6/20 (30%) in the MMF group compared with 0/19 (0%) in the CsA group (p = 0.02). Time to acute rejections was 4.0-28.7 months after withdrawal. Trough concentrations of mycophenolic acid (MPA) and CsA showed therapeutic levels. The subjects have been observed for eight yr, and of the 28 patients remaining on randomized therapy, the MMF patients preserved graft function better than CsA patients. Death-censored graft survival was 75% and 95% (p = 0.18) and patient survival was 70% and 68% (p = 0.99) in the MMF and CsA groups, respectively, at the end of long-term follow-up. CsA withdrawal was associated with a high rate of acute rejections. Initially, the treatment of acute rejections was successful. However, five of six lost their grafts in the long term.
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. anders.asberg@farmasi.uio.no
Anders
A
Åsberg
Terje
T
Apeland
Anna V
AV
Reisaeter
Aksel
A
Foss
Torbjørn
T
Leivestad
Kristian
K
Heldal
Lars O
LO
Thorud
Bjørn O
BO
Eriksen
Anders
A
Hartmann
D000208:Acute Disease; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome; D028761:Withholding Treatment
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D009173:Mycophenolic Acid