Risk factors of proteinuria and potentially protective effect of renin–angiotensin system inhibitors in patients with renal cell carcinoma receiving axitinib

PURPOSE: Patients receiving vascular endothelial growth factor-tyrosine kinase inhibitors are at a risk of developing proteinuria. Renin-angiotensin system (RAS) inhibitors exert renoprotective effects and might reduce proteinuria risk in these patients. We investigated the risk factors for and protective effect of RAS inhibitors against proteinuria in patients with renal cell carcinoma (RCC) receiving axitinib. METHODS: We retrospectively reviewed the medical records of patients with RCC receiving axitinib at Kobe City Medical Center General Hospital between September 2012 and October 2020. Patients with proteinuria ≥ 2+ at baseline were excluded. The patients were categorized into RAS inhibitor user, non-RAS inhibitor user, and non-user groups. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events, version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors for developing grade ≥ 2 proteinuria. RESULTS: Among 42 patients, 28 received antihypertensive drugs at baseline. Among these, 17 and 11 patients were in the RAS inhibitor and non-RAS inhibitor user groups, respectively. Twenty-three patients (54.8%) developed grade ≥ 2 proteinuria. The multivariate analysis revealed that the non-RAS inhibitor user group (P = 0.001) and patients with pre-existing grade 1 proteinuria (P = 0.022) were significantly associated with the development of grade ≥ 2 proteinuria, whereas the RAS inhibitor user group was not significantly associated with it. CONCLUSION: In patients with RCC receiving axitinib, pre-existing proteinuria and non-RAS inhibitor use were significantly associated with grade ≥ 2 proteinuria development. Our preliminary data should be confirmed by further studies.