Adding bevacizumab to cancer chemotherapy significantly increases the risk of high-grade proteinuria and nephrotic syndrome, according to a new report.

“It is important for medical oncologists, nephrologists, and patients to recognize the risk with adequate management to prevent renal failure and cardiovascular complications,” the authors concluded. Their findings appear in an upcoming issue of  the Journal of the American Society of Nephrology.

The researchers analyzed data from 16 studies that included a total of 12,268 patients who received bevacizumab as part of treatment for a variety of cancers. The studies compared chemotherapy plus bevacizumab with chemotherapy alone. Bevacizumab is a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, which plays a role tumor angiogenesis.

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The overall incidence of high-grade proteinuria with bevacizumab was 2.2%. Researchers observed the highest incidence—11.9%—in patients with renal cell carcinoma and the lowest incidence in patients with non-small cell lung cancer. Compared with chemotherapy alone, bevacizumab plus chemotherapy was associated with a nearly 4.8 times increased risk of high-grade proteinuria and 7.8 times increased risk of nephrotic syndrome.

The incidence of high-grade proteinuria also varied by dosage. Of 3,324 patients treated with low-dose bevacizumab (2.5 mg/kg/week), the incidence of high-grade proteinuria was 1.2%. Of 2,908 patients treated with high-dose bevacizumab (5 mg/kg/week), the incidence was 3%. Low- and high-dosage bevacizumab were associated with a 2.6 and 8.5 times increased risk of high-grade proteinuria.