Kidney transplant outcomes are related to tacrolimus, mycophenolic acid and prednisolone exposure in the first week

Barraclough, Katherine A., Staatz, Christine E., Johnson, David W., Lee, Katie J., McWhinney, Brett C., Ungerer, Jacobus P. J., Hawley, Carmel M., Campbell, Scott B., Leary, Diana R. and Isbel, Nicole M. (2012) Kidney transplant outcomes are related to tacrolimus, mycophenolic acid and prednisolone exposure in the first week. Transplant International, 25 11: 1182-1193.


Author Barraclough, Katherine A.
Staatz, Christine E.
Johnson, David W.
Lee, Katie J.
McWhinney, Brett C.
Ungerer, Jacobus P. J.
Hawley, Carmel M.
Campbell, Scott B.
Leary, Diana R.
Isbel, Nicole M.
Title Kidney transplant outcomes are related to tacrolimus, mycophenolic acid and prednisolone exposure in the first week
Journal name Transplant International   Check publisher's open access policy
ISSN 0934-0874
1432-2277
Publication date 2012-11
Sub-type Article (original research)
DOI 10.1111/j.1432-2277.2012.01553.x
Volume 25
Issue 11
Start page 1182
End page 1193
Total pages 12
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2013
Language eng
Formatted 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 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.
Keyword Immunosuppression
Kidney transplantation
Mycophenolic acid
Prednisolone
Tacrolimus
Open Access Mandate Compliance Yes - Open Access (Publisher DOI)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 5 September 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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