Administration of Bevacizumab and the Risk of Chronic Kidney Disease Development in Taiwan Residents: A Population-Based Retrospective Cohort Study

Abstract

Vascular endothelial growth factor (VEGF) plays a significant role as a pro-angiogenic and pro-permeability factor within the kidney. Bevacizumab is a pharmaceutical monoclonal anti-VEGF antibody that inhibits the growth of new blood vessels, which blocks blood supply and thereby restricts tumor growth. Thus, we conducted a nationwide study to explore the risk of chronic kidney disease (CKD) development in Taiwan residents after bevacizumab therapy. We drew data from the extensive National Health Insurance Research Database (NHIRD), which encompasses data from >99% of Taiwan’s population from 1995 onwards. Individuals who received bevacizumab between 2012–2018 were identified as the bevacizumab cohort, with the index date set at the first usage. We randomly selected dates within the study period for the control group to serve as index dates. We excluded patients with a history of CKD prior to the index date or those <20 years old. In both cohorts, patients’ propensity scores matched in a 1:1 ratio based on sex, age, index year, income, urbanization level, comorbidities, and medications. We found patients treated with bevacizumab had a significantly higher risk of contracting CKD than patients without bevacizumab (adjusted hazard ratio = 1.35, 95% confidence interval = 1.35–1.73). The risk of CKD was 1.35-fold higher in participants with bevacizumab treatment than those in the control group. These findings suggest that close monitoring of CKD development after bevacizumab administration is needed.

Nephrotoxicity of targeted therapy used to treat lung cancer

“…Bevacizumab, a recombinant human monoclonal antibody that binds to all known vascular endothelial growth factor A (VEGF-A) subtypes and exerts antiangiogenic effects by blocking the binding of VEGF-A to VEGF receptors (primarily VEGFR-1 and VEGFR-2) on the surface of endothelial cells, as VEGF-A binds to VEGFR-1 and VEGFR-2 to promote endothelial cell proliferation, activate survival pathways, and form new blood vessels. Therefore, bevacizumab plays an important role in the treatment of advanced cancer, including NSCLC ( 109 , 110 ). The most common renal impairment of bevacizumab is proteinuria in clinical practice ( 111 ).…”

“…Zhu et al ( 107 ) have shown that the incidence of all-grade hypertension was 21% and a significantly higher incidence in patients with renal cell carcinoma in a meta-analysis of total 4609 patients treated with sunitinib. In the treatment of lung cancer, bevacizumab is more likely to induce nephrotoxicity than other VEGF inhibitors ( 108 , 109 ).…”

“…In a pooled analysis of bevacizumab-treated patients including patients diagnosed NSCLC, the incidence of proteinuria of any grade was 8.2% and 4.6% in the bevacizumab and control groups, respectively, while the incidence of grade 3/4 proteinuria was 1.4% and 0.2%, respectively ( 108 ). Another population-based retrospective cohort study revealed that patients treated with bevacizumab had a significantly 1.35-fold higher risk of CKD than those who did not receive bevacizumab ( 109 ).…”