Introduction Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo+Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo+Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo+Bev for patients with unresectable HCC. Methods Sixty-four patients with Child-Pugh scores of 5–7, an eastern cooperative oncology group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein to creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. Results The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio (HR), 3.807; 95% confidence interval (CI), 1.579–9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614–24.010; p = 0.008) and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133–6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP > 135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR > 2 g/g Cr). Conclusion Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo+Bev.


中文翻译：

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接受 Atezolizumab 加贝伐单抗治疗不可切除的肝细胞癌患者早期出现蛋白尿的危险因素。

简介 蛋白尿是 atezolizumab 加贝伐单抗联合治疗 (Atezo+Bev) 的不良事件之一，可导致 Bev 使用中断。然而，尚未研究接受 Atezo+Bev 治疗的肝细胞癌 (HCC) 患者出现蛋白尿的危险因素。本研究的目的是确定 Atezo+Bev 治疗不可切除的 HCC 患者早期出现蛋白尿的危险因素。方法 64 例 Child-Pugh 评分为 5-7 分、东部肿瘤合作组表现状态为 0 或 1、蛋白尿水平较低（试纸测试和尿蛋白肌酐比值 (UPCR) 为 1+ 或更低）的患者分析治疗开始时低于 2.0 g/g Cr）。根据不良事件通用术语标准 5.0 版评估蛋白尿水平。我们采用UPCR代替24小时尿液采集进行定量检测。回顾性调查蛋白尿的发生率和肝功能的变化。结果 24 周内蛋白尿的累积发生率为 34.4%。多变量分析显示，估计肾小球滤过率较低（风险比 (HR)，3.807；95% 置信区间 (CI)，1.579–9.180；p = 0.003），高血压治疗（HR，6.224；95% CI，1.614– 24.010；p = 0.008）和高收缩压（SBP）（HR，2.649；95% CI，1.133-6.194；p = 0.025）是蛋白尿的危险因素。蛋白尿患者的血清白蛋白水平和白蛋白-胆红素评分恶化。此外，治疗期间平均收缩压 > 135 mm Hg 是发生严重蛋白尿 (UPCR > 2 g/g Cr) 的唯一危险因素。结论 我们的研究发现，控制血压对于接受 Atezo+Bev 治疗的 HCC 患者的蛋白尿管理极为重要。