Preventive Effect of Mineralocorticoid Receptor Antagonists Against Proteinuria Induced by Atezolizumab Plus Bevacizumab Therapy in Hepatocellular Carcinoma: A Multicenter Retrospective Study

Aim Mineralocorticoid receptor antagonists (MRAs) reduce proteinuria in chronic kidney disease, but their role in preventing bevacizumab‐induced proteinuria remains uncertain. This study aimed to assess whether MRAs prevent proteinuria caused by atezolizumab plus bevacizumab in patients with hepatocellular carcinoma. Methods The present retrospective study included patients with advanced hepatocellular carcinoma who received atezolizumab plus bevacizumab between September 2020 and December 2023 at five institutions in Japan. The primary outcome was the time to onset of grade ≥ 2 proteinuria during the first 6 months of bevacizumab treatment. Results Among 177 patients, 26 received MRAs and 151 did not. The onset of grade ≥ 2 proteinuria occurred significantly later in the MRA group than in the non‐MRA group ( p = 0.018). In multivariate Cox hazard analysis, diabetes (hazard ratio [HR] = 1.81, 95% confidence interval [CI]: 1.00–3.25, p = 0.049), higher average systolic blood pressure (HR = 2.08, 95% CI: 1.16–3.73, and p = 0.014), and MRA use (HR = 0.21, 95% CI: 0.047–0.90, and p = 0.035) were independently associated with time to grade ≥ 2 proteinuria. Bevacizumab interruption due to proteinuria within 6 months was lower in the MRA group than in the non‐MRA group (0% vs. 13.2% and p = 0.049). Conclusions MRA can suppress moderate or greater proteinuria induced by atezolizumab plus bevacizumab therapy and reduce the rate of bevacizumab interruption.