#601 Overweight-obese kidney transplant recipients have altered tacrolimus clearance and need lower doses for target levels with good graft outcomes

Abstract Background and Aims CYP3A4 which has been associated with altered tacrolimus (Tac) clearance. Clearances for drugs that are CYP3A4 substrates are generally reduced by 10%-35% in obese compared to normal-weight individuals. This study assessed the early and late Tac levels and weight-based total daily dose (TDD) for target Tac level in overweight-obese kidney transplant (KT) recipients and its relation to graft outcomes. Methods A retrospective study included 62 live-related KT recipients: overweight-obese KT recipients (N=32) with body mass index (BMI) >25 and normal-weight KT recipients (N=30) with BMI <25. The Tac level and weight-based TDD were examined in the 1st 3 months and 1 year after kidney transplantation with assessment of graft outcome. Results The overweight-obese patients' mean BMI was 31.29 and normal-weight patients' mean BMI was 22.20 p-value (0.0001). There was no significant difference between overweight-obese patients and normal-weight patients in mean Tac levels in 1st 3 months and after 1-year (mean 8.902, 6.99 ng/ml versus 8.906, 6.91 ng/ml respectively) p-values (0.992, 0.850) respectively. The weight-based TDD for target Tac level in 1st 3 months and after 1-year was significantly lower in overweight-obese than normal-weight patients (mean 0.108, 0.073 ng/ml versus 0.167, 0.102 ng/ml) respectively with p-value (0. 00035, 0.0076) respectively. KT recipients with BMI >30 showed lower weight-based TDD versus KT recipients with BMI 25-30 in 1st 3 months (0.094 versus 0.131 ng/ml) p-value (0.0255) while no difference after 1-year p-value (0.353). Graft outcomes did not significantly differ between overweight-obese versus normal-weight patients; the mean serum creatinine (1.22 versus 1.27 mg/dl) p-value (0.680) and graft rejection was (6 patients versus 6 patients) p-value (0.104) without graft loss. The weight-based TDD after 1-year was negatively correlated with BMI and transplant duration {r −0.369, p 0.003, r −0.278, p 0.028} respectively. Conclusion Overweight-obese patients have altered Tac clearance and they need lower doses to achieve target Tac level in the early and late periods post-transplant which is linked to good graft outcomes. According to these preliminary data the department is planning to study the effect of CYP 3A4/5 genetic polymorphisms on Tac dose requirement in most of these patients.