摘要
目的探讨他克莫司血药浓度及相关基因多态性与心脏移植术后新发糖尿病(NODAT)的相关性。方法拟纳入移植术前无糖尿病的心脏移植受者。收集患者资料并检测rs2237895、rs5215、rs2276706和rs8450四个单核苷酸多态性(SNPs)位点。根据美国糖尿病协会(ADA)诊断标准判断NODAT。采用多元logistic回归分析他克莫司血药浓度对NODAT的影响,并建立NODAT风险预测模型。结果共纳入101例心脏移植受者,其中NODAT 31例(30.7%)。NODAT组他克莫司剂量校正浓度(C 0/D)显著高于非NODAT组(139.3比96.0,P=0.025)。他克莫司C 0/D≥110 ng·mL-1/(mg·kg-1·d-1)[OR=4.52,95%CI(1.63,12.53),P=0.004]、年龄≥45岁[OR=4.99,95%CI(1.65,15.10),P=0.005]和体质量指数(BMI)≥25 kg·(m 2)-1[OR=3.70,95%CI(1.38,9.93),P=0.009]是NODAT的独立危险因素。在NODAT风险预测模型中加入他克莫司C 0/D≥110 ng·mL-1/(mg·kg-1·d-1)使风险预测模型的AUROC提高到0.788(P<0.001)。结论他克莫司C 0/D[≥110 ng·mL-1/(mg·kg-1·d-1)]、年龄(≥45岁)和BMI[≥25 kg·(m 2)-1]是NODAT发生的独立危险因素。基于以上危险因素建立的NODAT风险预测模型具有较好的预测效能,可便捷地初步筛选出心脏移植术后NODAT的高危人群,以便及时干预,预防NODAT的发生。
Objective To investigate the associations between tacrolimus trough concentrations and genetic polymorphisms and new onset diabetes after transplantation(NODAT)among heart recipients.Methods Heart recipients without diabetes before transplantation were eligible for the present study.Clinical data were collected and four single nucleotide polymorphisms(SNPs)of rs2237895,rs5215,rs2276706 and rs8450 were genotyped.NODAT was diagnosed according to the criteria of the American Diabetes Association(ADA).The effect of tacrolimus trough concentrations on NODAT were analyzed using multivariate logistic regression and NODAT risk predictive models were built.Results A total of 101 heart recipients were consecutively enrolled,31(30.7%)were diagnosed with NODAT.The dose-adjusted tacrolimus trough concentration(C 0/D)was significantly higher in the NODAT group than the non-NODAT group(median C 0/D 139.3 vs.96.0,P=0.025).Tacrolimus C 0/D≥110 ng·mL-1/(mg·kg-1·d-1)[OR=4.52,95%CI(1.63,12.53),P=0.004],age≥45 years[OR=4.99,95%CI(1.65,15.10),P=0.005]and BMI≥25 kg·(m 2)-1[OR=3.70,95%CI(1.38,9.93),P=0.009]were risk factors of NODAT.The area under the receiver operating characteristic curve(AUROC)of the model in predicting the NODAT risk increased to 0.788(P<0.001)when tacrolimus C 0/D≥110 ng·mL-1/(mg·kg-1·d-1)was added into predictive model.Conclusion Tacrolimus C 0/D[≥110 ng·mL-1/(mg·kg-1·d-1)],age(≥45 years)and BMI[≥25 kg·(m 2)-1]were independent risk factors of NODAT.The model built with these risk factors showed a good ability in predicting the risk of NODAT.Moreover,the model could easily identify the high-risk recipients of NODAT after heart transplantation,which would allow more timely preventive interventions to be made.
作者
张敏
蔡杰
张菁
袁拥华
韩勇
周红
ZHANG Min;CAI Jie;ZHANG Jing;YUAN Yonghua;HAN Yong;ZHOU Hong(Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Pharmacy,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Children’s Hospital of Chongqing Medical University,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China;Department of Cardiovascular Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
出处
《医药导报》
CAS
北大核心
2020年第10期1413-1418,共6页
Herald of Medicine
基金
国家自然科学基金资助项目(81703630)。
关键词
他克莫司
血药浓度
心脏移植
移植术后新发糖尿病
Tacrolimus
Trough concentrations
Heart transplantation
New onset diabetes after transplantation
