Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database

Abstract

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.