CYP3A5基因多态性及五酯胶囊对肾移植术后早期他克莫司暴露及不良反应的影响

Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients

目的 探讨CYP3A5基因多态性及五酯胶囊(WZ)对肾移植患者术后早期他克莫司暴露及不良反应的影响。方法 选择本院2021年9月至2023年9月接受同种异体肾移植术且术后接受他克莫司+霉酚酸类+泼尼松三联免疫治疗的患者132例为研究对象,根据其基因型(CYP3A5^(*)1或CYP3A5^(*)3/^(*)3)和是否联用WZ(联用为“+WZ”,不联用为“+NO WZ”)将患者分为4组。分析4组患者在肾移植术后14 d、1个月、3个月的他克莫司血药谷浓度/日剂量(c0/D)的差异,比较4组患者术后3个月内急性排斥反应及他克莫司相关不良反应的发生率。结果 术后14 d、1个月、3个月(CYP3A5^(*)1+WZ组患者除外),无论是否联用WZ,CYP3A5^(*)1基因型患者的c0/D均显著低于CYP3A5^(*)3/^(*)3基因型患者(P<0.05)。4组患者术后3个月内,虽急性排斥反应及他克莫司相关不良反应发生率差异均无统计学意义(P>0.05),但CYP3A5^(*)3/^(*)3+WZ组高血糖症发生率更高,达41.67%。结论 CYP3A5基因多态性与肾移植患者他克莫司c0/D显著相关。在监测他克莫司c0的前提下,CYP3A5^(*)1基因型患者应在术后尽早联用WZ以加快他克莫司达到治疗浓度范围,而CYP3A5^(*)3/^(*)3基因型患者由于高血糖症发生风险较高,不推荐联用WZ。

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule(WZ) on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients.METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes(CYP3A5^(*)1 or CYP3A5^(*)3/^(*)3) and with or without WZ (“ +WZ” meant drug combination,“+NO WZ” meant without combination).The blood trough concentration/daily dose(c0/D) values of the four groups were analyzed on the 14th day,1 month and 3 months after renal transplantation.The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups.RESULTS On the 14th day,1 month and 3 months after surgery(except for the CYP3A5^(*)1+WZ group),c_(0)/D values of CYP3A5^(*)1 genotype patients were significantly lower than those of CYP3A5^(*)3/^(*)3 genotype patients regardless of whether they were treated with WZ additionally(P<0.05).Within 3 months after surgery,although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups(P>0.05),the incidence of hyperglycemia in patients with CYP3A5^(*)3/^(*)3 was higher(41.67%).CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c_(0)/D in kidney transplant patients.Under the premise of c_(0) monitoring of tacrolimus,patients with CYP3A5^(*)1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range,while CYP3A5^(*)3/^(*)3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.