肾移植患者他克莫司血药浓度与肝肾毒性分析

目的分析我院肾移植患者他克莫司血药浓度的控制情况,探讨他克莫司血药浓度与肝肾功能之间的关系,以期为临床的合理用药提供依据。方法收集我院2011年11月至2013年4月96例肾移植患者他克莫司血药浓度的数据,及血药浓度测定当天的生化检测结果。根据他克莫司血药浓度（A）测定结果,将其分为4组（I组,A≤6 ng/mL；II组,6〈A≤10 ng/mL；III组,10〈A≤15 ng/mL；IV组,A〉15 ng/mL）,对4组中的各项生化指标及不良反应比例进行统计分析。结果红细胞（P=0.57）,血红蛋白（P=0.60）,血小板（P=0.12）,总胆红素（P=0.58）,谷氨酰基转移酶（P=0.46）,天门冬氨酸氨基转移酶（P=0.98）和丙氨酸氨基转移酶（P=0.40）在4组之间没有统计学意义；而白细胞（P=0.007）,碱性磷酸酶（P=0.004）和血尿素氮（P=0.007）在4组之间差异有统计学意义。当患者的他克莫司血药浓度维持在6-15 ng/mL 时,其肾小球滤过率估计值（estimated glo-merular filtration rate,eGFR）（70.2 mL/min）要明显高于≤6 ng/mL（58.2 mL/min）和〉15 ng/mL （66.2 mL/min）。同时,感染及中重度贫血的风险也较低,但他克莫司血药浓度与肝功能异常比例之间未发现显著的相关性。结论他克莫司血药浓度维持在6-15 ng/mL有利于患者肾功能的维持,同时能够降低感染和中重度贫血的风险,这一结果将有利于他克莫司的临床使用。

Analysis of the relationship between tacrolimus blood concentration with hepatotoxicity and nephrotoxicity in kidney transplant recipients

Objective In order to promote the rational use of tacrolimus,the effects of drug blood concentrations on kidney and liver functions were analyzed.Methods Ninety-six kidney transplant recipients between December 201 1 and April 2013 were enrolled in this study.According to the range of tacrolimus blood concentrations,four groups were subdivided,and the corresponding clinical parameters were recorded and analyzed.Results There were no significant differences among four groups in RBC （P=0.57）,HGB （P=0.6）,PLT （P=0.12）,TBIL （P=0.58）,GGT （P=0.46）, AST （P=0.98）and ALT （P=0.40）.However,significant differences were observed in WBC （P=0.007）,ALP （P=0.004）and BUN （P=0.007）.For the kidney transplant recipients,6-15 ng/mL might be an appropriate range for tacrolimus.Allograft function,evaluated by estimated glomerular filtration rate （eGFR）,in the range of 6-15 ng/mL （eGFR 70.2 mL/min）was significantly better than that in the ranges of≤ 6 ng/mL （eGFR 58.2 mL/min）and 〉15 ng/mL （eGFR 66.2 mL/min）. Meanwhile,patients had low risks of moderate/severe anemia and infection when TTC was maintained in the range of 6-1 5 ng/mL.There was no significant correlation between tacrolimus blood concentration and the rate of liver dysfunction.Conclusions The patients could maintain the relative normalkidney function,and have low risks of adverse events when tacrolimus blood concentration was in the range of 6-1 5 ng/mL.The results might be useful for the clinical application of tacrolimus.