Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Antivascular Endothelial Growth Factor-Related Proteinuria in Solid Tumors: A Systematic Review and Meta-Analysis.

Abstract

Anti-vascular endothelial growth factor (VEGF) therapy is widely used in the treatment of solid malignancies but is frequently complicated by proteinuria, which can affect treatment continuity and patient quality of life. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are commonly used to manage proteinuria in chronic kidney disease, their potential protective role against anti-VEGF-related proteinuria remains unclear. A systematic review and meta-analysis were conducted to evaluate the association between ACEi/ARB use and the risk of any-grade proteinuria in patients with solid tumors receiving anti-VEGF therapy. Comprehensive searches of PubMed, Embase, and Web of Science were performed for studies published between January 2000 and September 2025. Observational studies comparing ACEi/ARB users with patients receiving other antihypertensive agents were included. Patients not receiving antihypertensive therapy were excluded to minimize confounding by indication. Pooled risk ratios (RRs) were calculated using a random-effects model. Five retrospective observational studies were included. Across studies, ACEi/ARB use was associated with a significantly lower risk of any-grade proteinuria compared with other antihypertensive agents (pooled RR = 0.63; 95% confidence interval = 0.42-0.95), with moderate heterogeneity. Sensitivity analyses demonstrated consistent directionality of effect, supporting the robustness of the findings. ACEi/ARB use was associated with a reduced risk of any-grade proteinuria among patients receiving anti-VEGF therapy. Although limited by the observational nature of the evidence and geographic concentration of available studies, these findings suggest a potential renoprotective role of renin-angiotensin system inhibition in this setting. Prospective studies are warranted to confirm causality and clarify clinical implementation.