Department of Drug Safety and Risk Management, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Department of Clinical Data Management and Research, Clinical Research Center, National Hospital Organization Headquarters, Tokyo, Japan.
PLoS One. 2023 Aug 10;18(8):e0289950. doi: 10.1371/journal.pone.0289950. eCollection 2023.
Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.
蛋白尿是抗肿瘤药物贝伐珠单抗的主要副作用，但其在真实世界中的发生率和危险因素仍不清楚。尽管临床上使用肾素-血管紧张素-醛固酮系统抑制剂预防蛋白尿，但疗效仍不明确。本研究旨在揭示贝伐珠单抗诱导蛋白尿的发生率和危险因素，并探讨降压药物在预防蛋白尿中的有效性。我们使用国家医院组织临床数据档案和医学信息分析数据库进行了回顾性队列研究。纳入 2016 年 1 月 1 日至 2019 年 6 月 30 日期间接受贝伐珠单抗治疗的住院患者。研究结局为贝伐珠单抗治疗后 12 个月内发生蛋白尿。采用多变量逻辑回归分析比较蛋白尿患者和无蛋白尿患者的患者特征、实验室检查和药物使用情况。在 2458 例患者中，27%在接受贝伐珠单抗治疗后出现蛋白尿。护理依赖（比值比 [OR]，2.40；95%置信区间 [CI]，1.89-3.05；P<0.001）和收缩压≥140mmHg（OR，1.44；95%CI，1.17-1.79；P<0.001）被确定为危险因素。估计肾小球滤过率（eGFR）为 60-89、45-59 和<45mL/min/1.73m2 的患者发生蛋白尿的可能性分别比 eGFR≥90mL/min/1.73m2 的患者高 29.7%、76.8%和 66.0%。未观察到降压药物与蛋白尿发生之间存在显著关系。与以往报道相比，接受贝伐珠单抗治疗后可能有更多患者发生蛋白尿。护理依赖和收缩压是贝伐珠单抗诱导蛋白尿的预测危险因素。应密切监测有蛋白尿风险的患者。
