肝移植患者术后他克莫司血药浓度及肝肾功能的探讨

Study on tacrolimus concentration and liver and kidney function after liver transplantation

目的探讨肝移植术后患者他克莫司的血药浓度分布及肝肾功能情况。方法回顾性收集2015年9月至2019年10月于上海市第一人民医院行原位肝移植术后应用他克莫司治疗的66例患者临床资料,以及不同时期的他克莫司血药谷浓度及肝肾功能。结果66例患者30 d内他克莫司平均血药浓度(7.39±3.18)ng/ml,39%的患者血药浓度在6~10 ng/ml;90 d平均血药浓度为(6.32±3.09)ng/ml,58%的患者血药浓度在4~8 ng/ml;180 d平均血药浓度为(6.43±3.03)ng/ml,55%的患者血药浓度在4~8 ng/ml,均低于国内指南参考浓度;66例移植患者术后30 d内谷丙转氨酶和谷草转氨酶均恢复正常,术后180 d基本保持在正常范围内,与术前相比无统计学差异;肌酐(serum creatinine,Scr)在术后30 d内恢复,但180 d Scr明显高于术前,且差异有统计学意义(P<0.05)。他克莫司组的180 d Scr与术前相比,差异有统计学意义(P<0.05);他克莫司+西罗莫司组的180 d Scr与术前无差异。结论肝移植术后患者维持较低他克莫司有效浓度,既可发挥抗排异疗效,又不易引起不良反应;长期使用他克莫司易对肾脏蓄积性损伤。

Objective To investigate the distribution of blood concentration and liver and kidney function of tacrolimus in patients after liver transplantation.Methods The clinical data of 66 patients who underwent orthotopic liver transplantation in Shanghai General Hospital from September 2015 to October 2019 and were treated with tacrolimus regimen were retrospecticely collected,as well as the blood trough concentration of tacrolimus and liver and kidney function at different periods.Results The average blood concentration of tacrolimus in 66 patients whthin 30 days was(7.39±3.18)ng/ml,and 39% of patients had a blood concentration of 6—10 ng/ml.The average blood concentration in 90 days was(6.32±3.09)ng/ml,and 58% of patients had blood concentration was 4—8 ng/ml.The average blood concentration in 180 days was(6.43±3.03)ng/ml,and 55% of patients had blood concentration was 4—8 ng/ml,which was lower than the reference concentration of domestic guidelines.The alanine aminotransferase and aspartate aminotransferase in 66 patients gradually decreased to normal levels within 30 days after surgery,and remained basically within the normal range at 180 days after surgery,with no statistically significant difference compared with that before surgery.Serum creatinine(Scr)recovered within 30 days after surgery,but at D180 Scr was significantly higher than that before surgery,with statistical difference(P<0.05).In tacrolimus group,Scr was significantly different from that before operation at D180(P<0.05).In tacrolimus+sirolimus group,Scr did not differ from that before surgery at D180.Conclusion Low tacrolimus effective concentration after liver transplantation can exert anti-rejection therapy and not cause adverse reactions.Long-term use of tacrolimus is associated with cumulative renal injury.