Abstract
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.
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