Association between increased proteinuria induced by Bevacizumab, Ramucirumab, and Aflibercept and the risk of renal impairment and failure: a systematic review and meta-analysis.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.