富马酸替诺福韦二吡呋酯致肾损伤的主动监测与危险因素分析  

Active monitoring and risk factor analysis of tenofovir disoproxil fumarate-induced kidney injury

作　　者：王亚亚 丁丽[2] 史国琴 滕月鹏[1] 李彩东[1] 郭文娟[1] 缪苗苗[1] 魏秋芳 古殿杰 WANG Yaya;DING Li;SHI Guoqin;TENG Yuepeng;LI Caidong;GUO Wenjuan;MIAO Miaomiao;WEI Qiufang;GU Dianjie(Dept.of Pharmacy,the Second People’s Hospital of Lanzhou,Lanzhou 730046,China;Liver Disease Research Institute,the Second People’s Hospital of Lanzhou,Lanzhou 730046,China)

机构地区：[1]兰州市第二人民医院药剂科,兰州730046 [2]兰州市第二人民医院肝病研究所,兰州730046

出　　处：《中国药房》2022年第22期2770-2774,共5页China Pharmacy

基　　金：甘肃省药品监督管理局科研项目(No.2022GSMPA0039);兰州市人才创新创业项目(No.2018-RC-46);兰州市科技计划项目(No.2022-ZD-16)。

摘　　要：目的监测富马酸替诺福韦二吡呋酯(TDF)致肾损伤的发生情况并探讨其危险因素,为指导临床安全使用TDF提供参考。方法利用中国医院药物警戒系统(CHPS)收集2019年1月1日至2021年12月31日在兰州市第二人民医院使用TDF的乙型肝炎住院患者信息,根据肾损伤标准设置检索条件,对TDF致肾损伤疑似患者进行主动监测,再由临床药师逐一判定后确认TDF致肾损伤阳性患者,计算TDF致肾损伤发生率;分析纳入患者的基本信息、肝肾功能主要检验指标、合并疾病、合用药物情况与TDF致肾损伤的相关性,探索真实世界中TDF致肾损伤的危险因素。结果共纳入1226例使用TDF的乙型肝炎住院患者,经CHPS主动监测发现160例TDF致肾损伤疑似患者,最终人工确认64例阳性患者,TDF致肾损伤发生率为5.22%。与用药前相比,阳性患者用药后血肌酐、胱抑素C水平和尿蛋白2+及以上患者比例均显著升高(P<0.001),估测肾小球滤过率和血磷水平均显著降低(P<0.001),其余指标差异无统计学意义。患者用药时间超过36个月、疾病进展为肝硬化失代偿期、合用药物超过10种均与TDF致肾损伤有显著相关性(P<0.05或P<0.0125)。结论应用CHPS建立的TDF致肾损伤主动监测方案具有省时、省力、高效的特点;基于当前真实世界证据,当患者使用TDF时,应注意密切监测肾功能情况,尤其当用药时间较长、疾病进展为肝硬化失代偿期以及需要合用多种药物时,更应提高警惕,进而早期发现、有效规避高危患者不良反应风险。OBJECTIVE To monitor the occurrence of tenofovir disoproxil fumarate(TDF)-induced kidney injury and investigate the risk factors,and provide reference for rational use of TDF in clinic.METHODS The information of inpatients with hepatitis B was collected by China Hospital Pharmacovigilance System(CHPS)from the Second People’s Hospital of Lanzhou during Jan.1st,2019 to Dec.31st 2021.The search criteria were set according to kidney injury criteria,and suspected TDFinduced kidney injury cases were actively monitored;then the clinical pharmacist confirmed the positive patients with TDF-induced kidney injury one by one and calculated the incidence of TDF-induced renal injury;the risk factors for TDF-induced kidney injury in real world were explored by collecting and analyzing the correlation of basic data of patients,main indexes of liver and kidney function,complications and combined use of drugs with TDF-induced renal indexes.RESULTS Totally 1226 inpatients with hepatitis B using TDF were included.Through active monitoring of CHPS,160 suspected patients with TDF-induced kidney injury were found,and 64 positive patients were finally confirmed manually.The incidence of TDF-induced kidney injury was 5.22%.Compared with pre-medication,the levels of serum creatinine and cystatin C,the proportion of patients with urinary protein 2+and above were increased significantly after medication(P<0.001),glomerular filtration rate and blood phosphorus level were reduced significantly(P<0.001)and other indicators had no statistical difference.Treatment time for more than 36 months,disease progresses to decompensated cirrhosis,and concomitant use of more than 10 kinds of drugs were significantly correlated with TDFrelated kidney injury(P<0.05 or P<0.0125).CONCLUSIONS The active monitoring scheme of TDF-induced kidney injury established by CHPS has the characteristics of time-saving,labor-saving and high efficiency;based on real-world evidence,it is imperative to strengthen monitoring kidney function of patients when using TDF,especi

关 键 词：富马酸替诺福韦二吡呋酯 肾损伤 中国医院药物警戒系统 主动监测 药品不良反应 真实世界 

分 类 号：R978.7[医药卫生—药品] R969.3[医药卫生—药学]