Grant: Project Grant

Mycophenolic acid (MPA) is prescribed to almost all pediatric kidney transplant recipients to prevent their bodies from rejecting their new kidney. Unfortunately, even when taking consistent doses of this medication, many patients have large variations in MPA levels in their blood during the first 6 months post-transplant, which can cause severe side effects and loss of the organ. Almost a third of pediatric patients stop taking MPA within 2 years (majority within 6 months) of their transplant because they cannot tolerate the medication. These patients tend to experience worse outcomes (the other available anti-rejection drugs do not protect the organ as well) underscoring the urgent need to better understand this important drug. We still do not know why so many patients have variable MPA blood levels, and doctors do not know how to manage this problem effectively. Adding to this, the current method for monitoring and dosing MPA was adapted from adults and does not account for the unique drug actions (i.e., how the body handles the drug and how the drug affects the body) in pediatric patients. Using state-of-the-art "bench-to-bedside" methods, and working with 9 major transplant centres across Canada and United States, we aim to improve the precision dosing of MPA using samples collected from children for 6 months after their transplant to i) characterize how the blood levels of MPA are associated with side effects; ii) determine the patient factors which may influence the movement of MPA through the body; and iii) develop a model to aid MPA dosing and prevent the negative effects of MPA. The beneficial effects of our model will be determined directly in our patient population. Our lab has extensive expertise in describing the complex MPA drug actions using established drug measurement and modelling methods. This work will create a clinical tool to reduce the chances of MPA-associated negative outcomes and improve the quality of life of our transplant patients.