*Purpose: Pharmacogenetic profiling of transplant recipients has demonstrated marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus. Patients of African ancestry have been found to express loss-of-function mutations in the CYP3A5 gene less often than patients of other racial backgrounds, resulting in rapid metabolism of tacrolimus. Patients with this rapid metabolism require higher dosing to achieve adequate trough levels and are exposed to a greater risk of toxicity from elevated peak levels.

*Methods: The CYPA5 mutation status (*3,*6, or *7) of 286 adult AA kidney transplant (KTx) recipients (96%) was determined retrospectively using gene-wide analysis and categorized as 0 mutations (rapid metabolizers), 1 mutation (intermediate metabolizers), and 2 mutations (slow metabolizers). KTx outcomes (patient survival, kidney survival, and total Medicare spending) were determined using linked transplant registry and transplant claims data.

*Results: Among the cohort, 23% were rapid, 47% were intermediate, and 30% were slow metabolizers of tacrolimus. At 3 years, the rate of death-censored graft failure and all-cause graft failure was highest in the rapid metabolizers and lowest in the intermediate metabolizers (Figure). First-year Medicare reimbursement differed significantly (rapid, $79,535; intermediate, $72,796, and slow, $79,346, P=0.02). After adjustment for donor and recipient characteristics, intermediate metabolizers were $4400 less expensive than rapid metabolizers (P=.007).

*Conclusions: Pharmacogenomic assessment of AA KTx recipients may be useful to guide therapy, because CYPA5 status appears to be associated with outcome and spending after transplant.

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