CYP3A5 Polymorphisms Leading to Tacrolimus Toxicity Following an Adult Renal Transplant.

ABSTRACT

Tacrolimus is one of the calcineurin inhibitors used for maintaining immuno-suppression in thoracic and abdominal transplantations including heart, lung, liver, intestine, pancreas, and renal transplants. It has a narrow therapeutic window requiring therapeutic drug monitoring (TDM). Genetic polymorphism in the expression of cytochrome P3A5 enzyme plays a significant role in the bioavailability of tacrolimus in patients, leading to toxicity or rejection. In this case, we studied a renal transplant patient who received a standard dose of tacrolimus and experienced toxicity related to the poor expression of cytochrome P450 3A5 (CYP3A5), which required the withholding of tacrolimus and cutting the dose for several days with more frequent TDM. Similar cases have been reported before, yet there is no consensus on the appropriate dosage. The projected cost of additional TDM and hospitalization significantly exceeds the one-time cost of genetic CYP3A5 testing. In high-risk renal transplant recipients, pharmacogenetic testing must be considered to cut the time to limit TDM, prevent extended hospitalization, and reduce the total cost of transplantation.