Abstract
BACKGROUND: Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients. Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction. Tacrolimus, a calcineurin inhibitor, is metabolized differently based on cytochrome P450 3A (CYP3A)5 genetic variations and this impacts the graft outcome. AIM: To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation, emphasizing personalized immunosuppression strategies to optimize efficacy, minimize toxicity, and enhance long-term graft survival. METHODS: A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients. Patient demographics, medical history, CYP3A5 polymorphism, post-transplant investigations, graft biopsy results, preexisting comorbidities, history of post-kidney transplant infections, and new onset diabetes after transplantation (NODAT) was collected. Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors, with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant. Patients were followed regularly for one year for glomerular filtration rate (GFR), creatinine, and the tacrolimus trough concentration (ng/mL)/daily tacrolimus dose (mg/kg/day) ratio (C/D). A P value ≤ 0.05 was considered statistically significant. RESULTS: Kidney transplant recipients were classified as expressors (CYP3A51 carriers, n = 35) and non-expressors (CYP3A5*3*3, n = 60). Both groups were comparable for age, sex, and donor characteristics. Tacrolimus dose was comparable post-transplant except at 6 months and 12 months, where expressors required higher doses. Kidney function (creatinine and estimated GFR), NODAT, hypomagnesemia, and infections showed no significant differences between the two groups over 12 months of follow-up. Biopsy-proven acute rejection (BPAR) was found to be more in expressors (22.9% vs 13.3%, P = 0.2340) though it was not found to be statistically significant. Non-expressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups. CONCLUSION: CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors. BPAR was higher in expressors but the difference was not significant. Graft function, infection rate, and NODAT were comparable irrespective of CYP3A5 expression status, emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.