Document Detail


High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation.
MedLine Citation:
PMID:  20190242     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We hypothesized that a high within-patient variability in clearance of tacrolimus and mycophenolate mofetil (MMF) would put patients at risk for periods of over- or underimmunosuppression and would thus lead to long-term chronic allograft nephropathy and graft loss after transplantation. METHODS: From 297 patients transplanted between 1 January 2000 and 31 December 2004, the within-patient variability in clearance was calculated from tacrolimus whole-blood concentrations and mycophenolic acid (MPA) plasma concentrations drawn between 6 and 12 months post-transplantation. As a primary outcome, a composite end point consisting of graft loss, biopsy-proven chronic allograft nephropathy and 'doubling in plasma creatinine concentration in the period between t = 12 months post-transplantation and last follow-up' was used. RESULTS: In the study population of 297 patients, 34 patients reached the primary end point of graft failure. The within-patient variability in the clearance of tacrolimus and three other covariates are significant risk factors for reaching the composite end point of failure [P-values for intraindividual tacrolimus variability = 0.003, biopsy-proven acute rejection (BPAR) = 0.003, recipient age at transplantation = 0.005]. The mean tacrolimus concentration for controls [7.4 (+/- 2.9) ng/mL] and for failures [6.9 (+/- 2.5) ng/mL] was similar. Within-patient variability in the clearance of MPA was not related to reaching the composite end point of failure. CONCLUSIONS: This study shows a significant relationship between the high within-patient variability in the clearance of tacrolimus, but not for MPA, and long-term graft failure.
Authors:
Lennaert C P Borra; Joke I Roodnat; Judith A Kal; Ron A A Mathot; Willem Weimar; Teun van Gelder
Publication Detail:
Type:  Journal Article     Date:  2010-02-26
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  25     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-10-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  2757-63     Citation Subset:  IM    
Affiliation:
Department of Hospital Pharmacy, Molewaterplein 40, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Female
Graft Rejection / blood,  epidemiology*
Humans
Kidney Transplantation*
Male
Middle Aged
Mycophenolic Acid / analogs & derivatives*,  blood
Predictive Value of Tests
Regression Analysis
Retrospective Studies
Risk Factors
Tacrolimus / blood*
Transplantation, Homologous
Treatment Outcome
Chemical
Reg. No./Substance:
109581-93-3/Tacrolimus; 128794-94-5/mycophenolate mofetil; 24280-93-1/Mycophenolic Acid

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


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