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Randomized Trial Comparing Late Concentration-Controlled Calcineurin Inhibitor or Mycophenolate Mofetil Withdrawal
- Source :
- Transplantation, 93(9), 887-894
- Publication Year :
- 2012
-
Abstract
- Background Early calcineurin inhibitor (CNI) withdrawal with mycophenolate mofetil (MMF) has not become routine practice, due to concerns about excess acute rejection. Therapeutic drug monitoring may be advantageous when the CNI or MMF is withdrawn. Methods This prospective, randomized, concentration-controlled withdrawal study enrolled 177 stable renal transplant recipients on maintenance CNI-based immunosuppression, combined with steroids and MMF. After the feasibility phase of the study, patients were randomized to MMF-withdrawal (target area under the time-concentration curve-cyclosporine: 3250 ng·hr/mL or tacrolimus: 120 ng·hr/mL) or CNI-withdrawal (target area under the time-concentration curve-mycophenolic acid: 75 μg·hr/mL). Results The estimated glomerular filtration rate (modification of diet in renal disease) remained significantly better after CNI elimination (59.5±2.1 mL/min vs. 51.1±2.1 mL/min, P = 0.006) up to 3 years and resulted in less functional decline, including the subgroup with an estimated glomerular filtration rate less than 50 mL/min at baseline (P = 0.03). At 6 months, one patient in the MMF-withdrawal group (1.3%) and three in the CNI-withdrawal group (3.8%) experienced acute rejection (P = 0.62). The defined higher mycophenolic acid exposure was well tolerated. Conclusion These data indicate that with time the large majority of stable renal transplant recipients can be safely reduced to dual therapy with MMF or CNIs, applying concentration-controlled dosing. CNI-free patients, including those with moderate renal allograft dysfunction, have the benefit of improved renal function, whereas the risk of acute rejection after late withdrawal is low.
- Subjects :
- Graft Rejection
Male
medicine.medical_specialty
AUC
medicine.medical_treatment
Biopsy
Calcineurin Inhibitors
Urology
Renal function
Mycophenolic acid
law.invention
Kidney transplantation
Randomized controlled trial
law
Calcineurin inhibitor
Medicine
Humans
Dosing
Prospective Studies
Enzyme Inhibitors
Transplantation
medicine.diagnostic_test
Dose-Response Relationship, Drug
business.industry
Graft Survival
Mycophenolate mofetil
Immunosuppression
Middle Aged
Mycophenolic Acid
Tacrolimus
Calcineurin
Treatment Outcome
Therapeutic drug monitoring
Withdrawal
Acute Disease
Feasibility Studies
Kidney Failure, Chronic
Female
business
medicine.drug
Follow-Up Studies
Glomerular Filtration Rate
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Transplantation, 93(9), 887-894
- Accession number :
- edsair.doi.dedup.....e313538c90faf828651fc71225c5b8fc