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Renin–angiotensin system inhibitors for countering proteinuria induced by angiogenesis inhibitors: a retrospective observational analysis

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Abstract

Purpose

Occurrence of proteinuria could result in cessation of bevacizumab and ramucirumab treatments. Renin–angiotensin system (RAS) inhibitors exert a renoprotective effect by countering proteinuria. However, the association between renoprotective effect of RAS inhibitors and blood pressure control is unclear. This study assessed the risk factors for proteinuria induced by bevacizumab or ramucirumab and the relationship between renoprotective effect of RAS inhibitors and blood pressure control.

Methods

A retrospective observational analysis was conducted at Tokyo Women’s Medical University, Medical Center East from June 2015 to May 2018. Multivariate logistic regression analysis was used to identify risk factors for proteinuria induced by treatment with bevacizumab and ramucirumab. Renoprotective effect was assessed by analyzing blood pressure data in association with the use of RAS inhibitors.

Results

Out of 208 patients included in this study, proteinuria was observed in 50 (24%) patients. Body mass index ≥ 24 kg/m2 (OR = 2.45, 95% CI 1.21–4.96, p = 0.01), colorectal cancer (OR = 1.95, 95% CI 1.00–3.80, p < 0.05), and use of RAS inhibitors (OR = 0.25 95% CI 0.07–0.92, p = 0.04) were associated with proteinuria induced by treatment with bevacizumab and ramucirumab. A change in systolic blood pressure at second visit was higher in patients with RAS inhibitors compared with those in patients without RAS inhibitors (25 mmHg vs − 5 mmHg, p = 0.04).

Conclusion

Although RAS inhibitors protected patients from proteinuria induced by bevacizumab or ramucirumab, RAS inhibitors could not adequately control their blood pressures in patients with proteinuria.

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Funding

Financial support was not provided for this study.

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Authors and Affiliations

  1. Department of Pharmacy, Tokyo Women’s Medical University, Medical Center East, 2-1-10, Nishiogu, Arakawa-ku, Tokyo, 116-0011, Japan

    Toshinori Hirai, Yukari Shuji, Megumi Takiyama & Toshimasa Itoh

  2. Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Kazuhiko Hanada

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  1. Toshinori Hirai
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Correspondence to Toshinori Hirai.

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All procedures in this study involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. For this type of study, formal consent is not required.

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Hirai, T., Shuji, Y., Takiyama, M. et al. Renin–angiotensin system inhibitors for countering proteinuria induced by angiogenesis inhibitors: a retrospective observational analysis. Cancer Chemother Pharmacol 84, 195–202 (2019). https://doi.org/10.1007/s00280-019-03876-5

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  • DOI: https://doi.org/10.1007/s00280-019-03876-5

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