CYP3A5 Polymorphism in Renal Transplantation: A Key to Personalized Immunosuppression.

ABSTRACT

BACKGROUND: Tacrolimus is essential for the maintenance of immunosuppression after a kidney transplant. CYP3A5 is the gene that metabolizes tacrolimus, and polymorphism in this gene affects the metabolizing status. AIM: To assess the genetic polymorphism status of patients undergoing kidney transplantation and determine its impact on graft function and complications in the post-transplant period. METHODS: We retrospectively included the patients who had undergone a kidney transplant and had positive genetic polymorphism of the CYP3A5 gene. Based on loss of alleles, patients were categorized as non-expresser (loss of both alleles), intermediate expresser (loss of one allele), and expresser (no loss of allele) denoted by CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively. Data were analyzed with descriptive statistics. RESULTS: Of 25 patients, 60%, 32%, and 8% were non-expressers, intermediate-expressers, and expressers, respectively. The mean tacrolimus trough concentration to dose ratio after 6 months of the transplant was higher in non-expressers than intermediate-expressers and expressers (213 vs 85 and 46 ng/mL/mg/kg/d, respectively). The graft function was normal in all 3 groups except for graft rejection 1 patient in the expresser group. Compared with expressers, urinary tract infections (42.9% and 62.5%) and new-onset diabetes after transplantation (28.6% and 12.5%) were more frequent in non-expresser and intermediate expressers, respectively. The proportion of patients developing new-onset diabetes after transplantation was lower with the pre-transplant diagnosis of CYP3A5 polymorphism (16.7% vs 23.1%). CONCLUSION: Genotype-based dosing of tacrolimus helps achieve the desired therapeutic concentrations that can help to optimize graft outcomes and reduce the tacrolimus-related adverse effects. Pre-transplant evaluation of CYP3A5 can be more helpful in planning treatment strategies for optimized outcomes after kidney transplantation.