狼疮性肾炎患者他克莫司血药浓度监测与评价

Monitoring and evaluation of tacrolimus plasma concentration in patients with lupus nephritis

目的探究他克莫司在狼疮性肾炎(LN)患者治疗的有效浓度阈值,为临床用药的安全性和有效性提供参考。方法回顾性收集本院2016年1月至2022年5月应用他克莫司治疗LN患者(服药时间≥3个月)的临床及实验室检查数据,包括人口统计学信息(性别、年龄)、病程、实验室检查结果、用药情况、血药浓度监测数据及临床反应,进行疗效评价。本研究共纳入符合标准患者26例,共计91例次谷浓度监测。根据临床表现和生化指标将91例次血药浓度结果分为有效组(58例次)和无效组(33例次)。分析谷浓度(C0)与疗效相关性,受试者工作特征(ROC)曲线确定他克莫司有效浓度阈值。结果Logistics回归分析结果表明,C0和日给药剂量分别对疗效有显著性影响(P<0.001)。C0对于疗效的预判准确性优于给药剂量,ROC曲线下面积AUC为0.811 vs 0.756。此时对应的截点为4 ng·mL^(-1),提示当C0大于4 ng·mL^(-1)时,临床疗效阳性概率较高。结论他克莫司血药浓度与疗效存在相关性,ROC曲线分析初步确定其有效浓度的阈值为4 ng·mL^(-1)。

Objective To explore the effective concentration threshold of tacrolimus in the treatment of patients with lupus nephritis(LN),so as to provide reference for the safety and effectiveness of clinical medication.Methods Retrospectively collect the clinical and laboratory data of LN patients treated with tacrolimus(≥3 months)from January 2016 to May 2022,including demographic information(gender,age),the course of the disease,laboratory tests,medications,blood drug concentration monitoring data and clinical response,and to evaluate efficacy and safety.A total of 26 patients meeting the criteria were included in this study,with a total of 91 times of valley concentration monitoring.According to clinical manifestations and biochemical indexes,91 blood drug concentration results were divided into effective group(58 times)and ineffective group(33 times).The correlation between C0 and efficacy was analyzed,and the threshold of tacrolimus effective concentration was determined by receiver operating characteristic(ROC)curve.Results Logistic regression analysis showed that C0 and daily dose had significant effects on the efficacy(P<0.001).The predictive accuracy of C0 for efficacy was better than dose,and the AUC under ROC curve was 0.811 vs 0.756.At this time,the corresponding cut-off point was 4 ng·mL^(-1),suggesting that when C0 was greater than 4 ng·mL^(-1),the probability of positive clinical efficacy was higher.Conclusions The serum tacrolimus concentration was correlated with the curative effect,and the threshold of its effective concentration was initially determined to be 4 ng·mL^(-1) by ROC curve analysis。