Document Detail

Randomized trial comparing late concentration-controlled calcineurin inhibitor or mycophenolate mofetil withdrawal.
MedLine Citation:
PMID:  22538450     Owner:  NLM     Status:  MEDLINE    
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 Therapeutic drug monitoring may be advantageous when the CNI or MMF is withdrawn.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.
Jacqueline S Mourer; Jan den Hartigh; Erik W van Zwet; Marko J K Mallat; Jeroen Dubbeld; Johan W de Fijter
Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  93     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-07-24     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  887-94     Citation Subset:  IM    
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Acute Disease
Calcineurin / antagonists & inhibitors*
Dose-Response Relationship, Drug
Enzyme Inhibitors / administration & dosage
Feasibility Studies
Follow-Up Studies
Glomerular Filtration Rate
Graft Rejection / drug therapy*,  metabolism,  physiopathology
Graft Survival
Kidney Failure, Chronic / physiopathology,  therapy
Kidney Transplantation*
Middle Aged
Mycophenolic Acid / administration & dosage,  analogs & derivatives*
Prospective Studies
Treatment Outcome
Reg. No./Substance:
0/Enzyme Inhibitors; 24280-93-1/Mycophenolic Acid; 9242ECW6R0/mycophenolate mofetil; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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