UBC Theses and Dissertations
Investigating the impact of extended-release tacrolimus on adherence and graft outcomes in pediatric kidney transplant recipients Lang, Samantha
Improvements seen in short-term kidney transplant survival over the preceding three decades have not been reflected in long-term graft outcomes. This is particularly pertinent in the pediatric population, who experience high rates of graft failure, a large proportion of which are attributed to non-adherence. Extended-release tacrolimus (ER-Tac), taken once daily, is associated with improved adherence in adults but this has not been extensively studied in pediatric kidney transplant recipients. This study assessed 1) the clinical factors that influence conversion to ER-Tac 2) whether conversion to ER-Tac is associated with improved adherence and 3) whether conversion to ER-Tac is associated with improved allograft function and rejection outcomes. The first analysis showed that older age and female sex predicted conversion to ER-Tac. Adherence measures (medication adherence measure (MAM-MM) and tacrolimus trough variability (Tac CV%)), individual barriers to adherence, renal function, and rejection were not significant predictors of conversion. In the second analysis, we found that baseline adherence in this population was high and that ER-Tac was not subsequently associated with improved Tac CV% or self-reported adherence. Children were more likely to miss their morning medication and listed forgetfulness or schedule clashes as their most common reason to be non-adherent. Likewise, in the third analysis, ER-Tac was not superior to IR-Tac with regards to preventing rejection, decline in eGFR or graft loss. Older age and female sex have been associated in other studies with poorer allograft outcomes and perhaps act as a high-level risk assessment for conversion to ER-Tac based on perception of risk. We did not find that age or sex were strongly associated with adherence or outcomes in multivariable analyses in this study. The lack of association between ER-Tac and adherence may be explained by a high baseline adherence in this population and because patients were not selected for conversion based on adherence behaviour. The finding of stable late graft outcomes between IR-Tac and ER-Tac remains important, especially given patient preference for ER-Tac regarding convenience and quality of life reported in other studies.
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