Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data

BACKGROUND: Proteinuria is a common adverse effect of vascular endothelial growth factor targeted agents, particularly in metastatic renal cell carcinoma (mRCC). However, risk factors for proteinuria are poorly defined. METHODS: Data on 1392 mRCC patients using pazopanib or sunitinib were pooled from two Phase-III clinical trials. Risk factors and prognostic effect of on-therapy proteinuria were evaluated by Cox proportional hazards regression. RESULTS: Any-grade (1–4) and grade 3/4 proteinuria incidence were 15.0% and 3.7%, respectively. Asian ethnicity, diabetes, baseline systolic blood pressure (SBP), pre-existing grade 1 proteinuria and prior nephrectomy were significant independent predictors of either any-grade or grade 3/4 proteinuria. Proteinuria, particularly grade 3/4 (adjusted hazard ratio 0.53 (95% confidence interval 0.30–0.92)), was associated with improved overall survival. CONCLUSIONS: In mRCC patients using pazopanib or sunitinib, Asian ethnicity, diabetes, SBP, pre-existing proteinuria and prior nephrectomy were independent predictors of on-therapy proteinuria, which was associated with improved survival.