Shibutani Yuma, Nishizaki Maki
Department of Pharmacy, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Int J Clin Oncol. 2025 Jul 5. doi: 10.1007/s10147-025-02819-w.
Treatment with bevacizumab, ramucirumab, and aflibercept increases the risk of developing proteinuria; however, their association with the risk of renal impairment or failure remains unknown, warranting further investigation.
Consequently, a systematic review and meta-analysis were conducted to quantify the exact risk and incidence of proteinuria, renal impairment, and renal failure associated with bevacizumab, ramucirumab, and aflibercept therapy. We searched the PubMed, Cochrane Library, and Web of Science databases for phase III randomized controlled trials (RCTs) of these therapies published before November 5, 2024.
The meta-analysis included 29,165 patients from 47 RCTs, including 14,211 patients who received bevacizumab, ramucirumab, and aflibercept. The incidence of proteinuria was 24% (95% confidence interval [CI] 18-33) for all-grades and 3% (95% CI 2-4) for grades ≥ 3 proteinuria. Compared with controls, the addition of these medications was associated with an increased risk of developing all grades of proteinuria (odds ratio [OR]: 7.32; 95% CI 5.17-10.3), as well as grades ≥ 3 proteinuria (OR: 7.05; 95% CI 5.52-9.00). The risk of all-grade (OR: 1.54; 95% CI 1.21-1.96) and grade ≥ 3 (OR; 1.64, 95% CI 1.08-2.24) renal impairment significant increased with additional treatment with these drugs. However, no significant increase in risk was observed for renal failure at any grade (OR: 1.26; 95% CI 0.92-1.72).
Bevacizumab, ramucirumab, and aflibercept significantly increased the risk of developing proteinuria and renal impairment, but not renal failure. Monitoring and managing renal function and proteinuria in patients treated with these drugs is crucial.
使用贝伐单抗、雷莫西尤单抗和阿柏西普治疗会增加蛋白尿的发生风险；然而，它们与肾功能损害或衰竭风险之间的关联仍不清楚，需要进一步研究。
因此，我们进行了一项系统评价和荟萃分析，以量化与贝伐单抗、雷莫西尤单抗和阿柏西普治疗相关的蛋白尿、肾功能损害和肾衰竭的确切风险及发生率。我们在PubMed、Cochrane图书馆和Web of Science数据库中检索了2024年11月5日前发表的这些治疗方法的III期随机对照试验（RCT）。
荟萃分析纳入了来自47项RCT的29165例患者，其中14211例接受了贝伐单抗、雷莫西尤单抗和阿柏西普治疗。所有级别的蛋白尿发生率为24%（95%置信区间[CI]18-33），≥3级蛋白尿发生率为3%（95%CI CI 2-4）。与对照组相比，添加这些药物会增加各级蛋白尿的发生风险（比值比[OR]：7.32；95%CI 5.17-10.3），以及≥3级蛋白尿的发生风险（OR：7.05；95%CI 5.52-9.00）。使用这些药物进行额外治疗后，所有级别（OR：1.54；95%CI 1.21-1.96）和≥3级（OR；1.64，95%CI 1.08-2.24）肾功能损害的风险显著增加。然而，任何级别的肾衰竭风险均未观察到显著增加（OR：1.26；95%CI 0.92-1.72）。
贝伐单抗、雷莫西尤单抗和阿柏西普显著增加了蛋白尿和肾功能损害的风险，但未增加肾衰竭的风险。对接受这些药物治疗的患者监测和管理肾功能及蛋白尿至关重要。
