Elucidation of optimal proteinuria management based on the risk of ramucirumab-induced proteinuria

Proteinuria is a dose-limiting adverse effect of ramucirumab treatment, which is an anti-angiogenic agent that targets the human vascular endothelial growth factor. The predictors of proteinuria have not been completely elucidated and there is currently no consensus. The present study aimed to identify the risk factors for ramucirumab-induced proteinuria and to determine an optimal proteinuria management. A total of 145 patients who received ramucirumab at Ogaki Municipal Hospital (Ogaki, Japan) between September 2015 and March 2021 were retrospectively studied. Multivariate logistic regression analysis was conducted to evaluate the association between the patient baseline characteristics and the development of proteinuria following ramucirumab treatment. Furthermore, the time of proteinuria onset and of the worst qualitative proteinuria were recorded. Proteinuria (>2+) following ramucirumab was independently associated with lung cancer [odd ratio (OR): 0.232, 95% confidence interval (CI): 0.061-0.874; P=0.031] and proteinuria at the start of treatment [qualitative test (+/-); OR: 4.760, 95% CI: 1.360-16.700; P=0.041]. The median time of onset of proteinuria was 56 days (time range, 7-414 days), and the median time when the worst qualitative results were observed was 83 days (time range, 7-442 days). The >2+ proteinuria in the qualitative test was observed in 27 out of the 82 patients with gastric cancer (P=0.041), 8/21 patients with colon cancer (P=0.188), and in 3 out of the 37 patients with lung cancer (P=0.003). The prevalence of proteinuria was low in patients with lung cancer, and proteinuria (>2+) was likely to occur when the proteinuria at the start of ramucirumab was (+/-) by qualitative test. The results from the present study indicated that particular attention should be paid to proteinuria at the start of treatment when monitoring proteinuria as an adverse event of ramucirumab treatment.