他克莫司血药浓度不达标风险预测模型的建立及验证  

Development and Validation of a Risk Prediction Model for Tacrolimus Blood Concentration Failure

作　　者：李增 尹钊[1] 杜书章[1] LI Zeng;YIN Zhao;DU Shuzhang(Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450052

出　　处：《中国药学杂志》2024年第10期945-950,共6页Chinese Pharmaceutical Journal

摘　　要：目的分析肾移植患者他克莫司(FK506)血药浓度不达标的影响因素,并构建风险预测列线图模型。方法选取2020年6月至2023年6月医院收治的肾移植术后服用FK506治疗并监测30 d内血药浓度的200例患者为研究对象,根据监测结果将其分为达标组(5~15μg·L^(-1))126例和未达标组(<5μg·L^(-1)或>15μg·L^(-1))74例,收集两组患者的临床资料,采用单因素和多因素Logistic回归分析筛选FK506血药浓度不达标的独立危险因素,据此构建FK506血药浓度不达标的风险列线图预测模型并进行拟合优度检验。结果术后30 d内200例患者的1200次FK506浓度监测中,达到目标浓度5~15μg·L^(-1)的次数为756次,达标率为63.0%。其中达到目标浓度的患者共126例(达标组),未达到目标浓度的患者共74例(未达标组)。未达标组年龄>60岁、男性、静脉注射、空腹血糖>7 mmol·L^(-1)、总胆红素>20μmol·L^(-1)、白细胞计数≤4×10^(9)·L^(-1)、血肌酐>133μmol·L^(-1)的患者比例均高于达标组,差异有统计学意义(P<0.05)。多因素Logistic回归分析,结果显示,年龄>60岁、男性、空腹血糖>7 mmol·L^(-1)、总胆红素>20μmol·L^(-1)、血肌酐>133μmol·L^(-1)为肾移植患者FK506血药浓度不达标的独立危险因素(均P<0.05)。构建的列线图模型AUC达到0.859(0.795~0.924),模型校准曲线验证C-index为0.836,H-L偏差度检验χ^(2)=4.203,P=0.516,校正曲线与理想曲线走势基本一致,精准度和区分度良好,决策曲线(DCA)分析显示,列线图预测模型显示的阈值概率(0.05~0.95)范围较大,其对应红色曲线到灰色曲线和横坐标轴的面积最大,表明模型临床效用价值较好。结论年龄>60岁、男性、空腹血糖>7 mmol·L^(-1)、总胆红素>20μmol·L^(-1)、血肌酐>133μmol·L^(-1)是肾移植患者FK506血药浓度不达标的危险因素,据此构建的列线图模型能有效预测肾移植患者FK506血药浓度不达标风险程度。OBJECTIVE To analyze the influencing factors of tacrolimus(FK506)blood concentration non-attainment in renal transplant patients and construct a risk prediction column-line diagram model.METHODS Two hundred patients admitted to the hospital from June 2020 to June 2023 who were treated with FK506 after renal transplantation and whose blood concentration was monitored for 30 d were selected for the study,and according to the monitoring results,they were categorized into 126 cases in the group of meeting the standard(5-15μg·L^(-1))and 74 cases in the group of failing to meet the standard(<5μg·L^(-1)or>15μg·L^(-1)),and the clinical data were collected,and independent risk factors for failing to meet the standard of FK506 were screened and fit into a predictive model by single-factor and multifactorial logistic regression analysis.Clinical data of the two groups were collected,and the independent risk factors for FK506 blood concentration non-compliance were screened by single-factor and multifactor logistic regression analyses,according to which,a prediction model for the risk of FK506 blood concentration non-compliance was constructed with a line graph and tested for goodness-of-fit.RESULTS Of the 1200 FK506 concentration monitoring sessions in 200 patients within 30 d after surgery,the number of sessions in which the target concentration of 5-15μg·L^(-1)was reached was 756,with an attainment rate of 63.0%.A total of 126 patients reached the target concentration(target group),and 74 patients did not reach the target concentration(non-target group).The proportion of patients with age>60 years,male,intravenous,fasting blood glucose(FPG)>7 mmol·L^(-1),total bilirubin(TB)>20μmol·L^(-1),white blood cell count(WBC)≤4×10^(9)·L^(-1),and blood creatinine(Cr)>133μmol·L^(-1)was higher in the non-attainment group than in the attainment group,and the difference was statistically significant(P<0.05).Multifactorial logistic regression analysis was performed,and the results showed that age>60 years,male,FPG>7 mmol�

关 键 词：他克莫司 血药浓度 危险因素 风险预测模型 

分 类 号：R969.1[医药卫生—药理学]