Kidney transplant outcomes are related to tacrolimus, mycophenolic acid and prednisolone exposure in the first week
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 AUC0–12, P = 0.02; 0.23 change in odds for a SD increase in MPA AUC0–12, 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 AUC0–12, P = 0.04; 0.40 change in odds for a SD increase in total prednisolone AUC0–6, 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.
Document Type: Research Article
Affiliations: 1: Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Brisbane, Qld, Australia 2: School of Pharmacy, University of Queensland, Brisbane, Qld, Australia 3: Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Qld, Australia
Publication date: November 1, 2012