Title |
Kidney transplant outcomes are related to tacrolimus, mycophenolic acid and prednisolone exposure in the first week
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Published in |
Transplant International, September 2012
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DOI | 10.1111/j.1432-2277.2012.01553.x |
Pubmed ID | |
Authors |
Katherine A. Barraclough, Christine E. Staatz, David W. Johnson, Katie J. Lee, Brett C. McWhinney, Jacobus PJ. Ungerer, Carmel M. Hawley, Scott B. Campbell, Diana R. Leary, Nicole M. Isbel |
Abstract |
This study analysed associations between tacrolimus, mycophenolic acid (MPA) and prednisolone exposures on day 4 and month 1 post kidney transplant and clinical outcomes. Area under the concentration-time curve (AUC) for each drug was estimated using validated multiple regression-derived limited sampling strategies. Multivariate logistic regression was used to associate drug exposure with clinical outcomes. One hundred and twenty subjects were studied. Between-subject variability in dose-adjusted exposure to each medication was high. Both day 4 tacrolimus and MPA exposures were independently predictive of delayed graft function (2.6 change in odds for a standard deviation (SD) increase in tacrolimus AUC(0-12) , P = 0.02; 0.23 change in odds for a SD increase in MPA AUC(0-12) , P = 0.02). Both day 4 MPA and total prednisolone exposures were independently predictive of rejection (0.20 change in odds for a SD increase in MPA AUC(0-12) , P = 0.04; 0.40 change in odds for a SD increase in total prednisolone AUC(0-6) , P = 0.03). Lowest tertile exposure to all three immunosuppressant medications imposed significantly higher odds of rejection [adjusted odds ratio 34.2 (95% CI 4.1, 284.4), P = 0.001]. This study highlights the importance of achieving early target exposure and suggests a potential role for individualized initial dosing or early therapeutic monitoring of all three immunosuppressive agents. |
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Mendeley readers
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