Abstract
Background
Proteinuria is a common adverse event observed during treatment with antivascular endothelial growth factor (VEGF) antibodies. Proteinuria is a risk factor for renal dysfunction and cardiovascular complications in patients with chronic kidney disease. However, the association between anti-VEGF antibody-induced proteinuria and renal dysfunction or cardiovascular complications remains unclear.
Methods
This retrospective, observational study included patients with cancer that were treated with bevacizumab (BV) at Kyoto University Hospital (Kyoto, Japan) between January 2006 and March 2018. Adverse event rates were compared between patients who developed qualitative ≥ 2 + proteinuria and those who developed < 1 + proteinuria. Adverse events were defined as renal dysfunction (i.e., ≥ 57% decrease in the eGFR, compared to the rate at the initial treatment) and hospitalization due to BV-associated cardiovascular complications and other adverse events.
Results
In total, 734 patients were included in this analysis. Renal dysfunction was more common in patients with ≥ 2 + proteinuria than in those with < 1 + proteinuria (13/199, 6.5% vs. 12/535, 2.3%). Seven of these 13 patients with ≥ 2 + proteinuria had transient reversible renal dysfunction. Only four (2.0%) patients had BV-associated renal dysfunction. Of the 734 patients, six patients, 16 patients, and 13 patients were hospitalized because of the adverse events of cardiovascular complications, thromboembolisms, and cerebrovascular complications, respectively. No relationship was observed between these adverse events and proteinuria.
Conclusion
BV treatment-induced proteinuria was not associated with renal dysfunction or other adverse events. Continuing BV with caution is a possible treatment option, even after proteinuria develops, in patients with cancer and a limited prognosis.
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Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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The authors would like to thank all participants and their families.
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All listed authors contributed to the study conception and design. Data collection and analysis were performed by SK, YN, MS, EU, SH, SY, KS and TM. The first draft of the manuscript was written by SK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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MY received honoraria and scholarship donations outside the submitted work from Chugai Pharmaceutical Co., Ltd. MM received research funding outside the submitted work from Chugai Pharmaceutical Co., Ltd.
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10147_2024_2474_MOESM1_ESM.pdf
Supplementary file1 Patients who developed quantitative 3+ proteinuria. Data of the primary cancer site and total number of bevacizumab (BV) administrations are presented in the bar plot. Black bars indicate patients in whom BV administration was continued, even when 3+ proteinuria appeared for the first time. Gray bars indicate patients in whom the drug administration was skipped or discontinued (PDF 24 KB)
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Kataoka, S., Nishikawa, Y., Funakoshi, T. et al. Proteinuria frequency and subsequent renal dysfunction in bevacizumab-treated patients: a single center, retrospective, observational study. Int J Clin Oncol 29, 398–406 (2024). https://doi.org/10.1007/s10147-024-02474-7
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DOI: https://doi.org/10.1007/s10147-024-02474-7