Plasma endothelin-1 may predict bevacizumab-induced proteinuria in patients with colorectal cancer

Proteinuria is one of the most common adverse events leading to the discontinuation of bevacizumab therapy. We analyzed plasma ET-1 levels as an indicator of renal endothelial dysfunction in colorectal cancer patients, to determine the utility of plasma ET-1 for identification of patients at high risk of proteinuria when treated with bevacizumab.

Patients (n = 40) were recruited from an outpatient chemotherapy center between December 2020 and January 2022. Blood samples for plasma ET-1 levels were collected before treatment with bevacizumab (baseline), and after treatment for 3 and 6 months, and plasma ET-1 was determined by ELISA. Proteinuria was evaluated based on CTCAE v5.0 using urine protein-creatinine ratio instead of 24-h urine protein.

Plasma ET-1 levels at baseline were significantly higher in the group with grade ≥ 2 proteinuria than in the non-proteinuria group (p = 0.019). After adjusting for age, systolic and diastolic blood pressure, and hypertension following bevacizumab, plasma ET-1 levels at baseline were found to be an independent predictor of development of grade ≥ 2 proteinuria (OR = 17.8, 95% CI 1.42-223, and p = 0.026). Receiver operating characteristic curve analysis indicated an optimal cut-off value of the plasma ET-1 level of 1.19 pg/mL for predicting grade ≥ 2 proteinuria, with a sensitivity of 80.0% and specificity of 73.3%.

In conclusion, higher plasma ET-1 levels before treatment might increase the risk of proteinuria in colorectal cancer patients treated with bevacizumab. This might have important implications in the early detection of the risk of proteinuria.