Page 92 - 《中国药房》2022年22期

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
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王亚亚 ，丁 丽 ，史国琴 ，滕月鹏 ，李彩东 ，郭文娟 ，缪苗苗 ，魏秋芳 ，古殿杰（1.兰州市第二人民医院药
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剂科，兰州 730046；2.兰州市第二人民医院肝病研究所，兰州 730046）
中图分类号 R978.7；R969.3 文献标志码 A 文章编号 1001-0408（2022）22-2770-05
DOI 10.6039/j.issn.1001-0408.2022.22.17
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 1 226 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＜0.012 5）。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。
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

Active monitoring and risk factor analysis of tenofovir disoproxil fumarate-induced kidney injury
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WANG Yaya ，DING Li ，SHI Guoqin ，TENG Yuepeng ，LI Caidong ，GUO Wenjuan ，MIAO Miaomiao ，WEI
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Qiufang ，GU Dianjie（1. Dept. of Pharmacy， the Second People’s Hospital of Lanzhou， Lanzhou 730046，
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China；2. Liver Disease Research Institute， the Second People’s Hospital of Lanzhou， Lanzhou 730046， China）
ABSTRACT 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 TDF-
induced 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 1 226 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 TDF-
related kidney injury （P＜0.05 or P＜0.012 5）. 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， especially when the patient has been on
medication for a long time， in decompensated cirrhosis and
Δ 基金项目 甘肃省药品监督管理局科研项目（No.2022GSMPA00
combination of multiple drugs， and thus， we can identify
39）；兰州市人才创新创业项目（No.2018-RC-46）；兰州市科技计划项
earlier and avoid adverse effects in high-risk patients
目（No.2022-ZD-16）
effectively.
＊第一作者 主管药师，硕士。研究方向：药品不良反应。电话：
0931-8373316。E-mail：1328019908@qq.com KEYWORDS tenofovir disoproxil fumarate； kidney injury；
# 通信作者 主任药师，硕士。研究方向：临床药学、药事管理。电 China Hospital Pharmacovigilance System； active monitoring；
话：0931-8361836。E-mail：393916208@qq.com adverse drug reaction； real world

· 2770 · China Pharmacy 2022 Vol. 33 No. 22 中国药房 2022年第33卷第22期