Preemptive Pharmacogenetics in Renal Transplantation: A Real-World Assessment of Pharmacogenetic Actionability

BACKGROUND: Pharmacogenetics (PGx) is increasingly recognized as an important component of personalized medicine. In kidney transplantation, where immunosuppressive therapies and comedications often have narrow therapeutic index, preemptive PGx could complement therapeutic drug monitoring to improve individualized care. This study aimed to investigate the value of implementing PGx testing in the pretransplant assessment of renal transplant recipients. METHODS: This single-center retrospective study included 110 adult patients who underwent a pretransplant PGx assessment between January 1, 2022, and June 30, 2023. The analysis focused on 16 pharmacogenes shared between the local routine PGx panel and the publicly available ClinPGx guideline support interface, with some genes analyzed using hotspot-only coverage. Medication lists were extracted at 2 time points: pretransplant and post-transplant (or last follow-up for patients on waiting list). Theoretical actionability was defined as the presence of at least 1 actionable genotype, and effective actionability as at least 1 actionable gene-drug pair according to international guidelines. RESULTS: Theoretical actionability was observed in 109 of 110 patients (99%). Effective actionability concerned 29 of 110 patients (26%) at the pretransplant assessment and 19 of 41 (46%) at the post-transplant stage. The most frequent actionable gene-drug pairs at the latter stage included CYP2C19-proton pump inhibitors (38%), CYP3A5-tacrolimus (25%), SLCO1B1-statins (13%), CYP2D6-tramadol (8%), and ABCG2-allopurinol (8%). CONCLUSIONS: Preemptive PGx embedded in the pretransplant evaluation identifies clinically relevant gene-drug interactions. In combination with therapeutic drug monitoring, this approach has the potential to optimize immunosuppressive drugs initiation and support pharmacological management in kidney transplantation.