他克莫司与肾移植术后糖尿病相关性的单中心研究

Correlation between tacrolimus and diabetes mellitus after kidney transplantation:a single center study

目的探讨移植后糖尿病(PTDM)的主要危险因素,分析他克莫司与肾移植PTDM发生的相关性。方法收集123例肾移植受者的临床资料,分为PTDM组(19例)和非PTDM组(104例)。分析两组受者的临床资料,采用二元logistic回归分析PTDM的危险因素。将24只小鼠分为对照组(生理盐水),他克莫司低剂量组(0.1 mg/kg)、中剂量组(0.75 mg/kg)和高剂量组(1.5 mg/kg),每组各6只,分别每日注射2次。分析他克莫司对小鼠血糖代谢的影响。结果肾移植术后1年内PTDM发生率为15.4%(19/123)。受者年龄≥48岁、移植术后3个月他克莫司谷浓度≥9 ng/mL是肾移植术后发生PTDM的危险因素(均为P<0.05)。低剂量组、中剂量组和高剂量组小鼠给药后的空腹血糖水平低于给药前(均为P<0.05),但不具有剂量依赖性(P=0.750)。低剂量组、中剂量组和高剂量组小鼠给药后餐后血糖水平高于给药前(均为P<0.05),且呈现他克莫司剂量依赖性(P=0.012)。结论他克莫司与肾移植术后PTDM发生密切相关,受者年龄≥48岁、移植术后3个月他克莫司谷浓度≥9 ng/mL是PTDM发生的独立危险因素。他克莫司以剂量依赖性的方式影响小鼠餐后血糖水平。

Objective To explore the major risk factors of post transplantation diabetes mellitus(PTDM)and analyze the correlation between tacrolimus and PTDM after kidney transplantation.Methods Clinical data of 123 kidney transplant recipients were collected.All recipients were divided into the PTDM group(n=19)and non-PTDM group(n=104).Clinical data of all recipients in two groups were analyzed.The risk factors of PTDM were analyzed by binary logistic regression.Twenty-four mice were evenly divided into the control group(normal saline),low-dose tacrolimus(0.1 mg/kg),medium-dose tacrolimus(0.75 mg/kg)and high-dose tacrolimus groups(1.5 mg/kg).The solutions were given twice a day.The effect of tacrolimus on blood glucose metabolism in mice was evaluated.Results The incidence of PTDM was 15.4%(19/123)within 1 year after kidney transplantation.Age≥48 years old and the trough concentration of tacrolimus≥9 ng/mL within 3 months after kidney transplantation were the risk factors for PTDM after kidney transplantation(both P<0.05).The fasting blood glucose levels of mice after administration in the low-,medium-and high-dose tacrolimus groups were significantly lower than those before administration(all P<0.05)in a dose-independent manner(P=0.750).In the low-,medium-and high-dose tacrolimus groups,the postprandial blood glucose levels of mice after administration were significantly higher than those before administration(all P<0.05)in a dose-dependent manner(P=0.012).Conclusions Tacrolimus is intimately correlated with the incidence of PTDM after kidney transplantation.Age≥48 years old and the trough concentration of tacrolimus≥9 ng/mL within 3 months after kidney transplantation are the independent risk factors of PTDM.Tacrolimus affects the postprandial blood glucose levels of mice in a dosedependent manner.