Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 195–202 | Cite as

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

  • Toshinori HiraiEmail author
  • Yukari Shuji
  • Megumi Takiyama
  • Kazuhiko Hanada
  • Toshimasa Itoh
Original Article



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.


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.


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).


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.


Bevacizumab Ramucirumab Proteinuria Renin–angiotensin system inhibitors Blood pressure 



Financial support was not provided for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyTokyo Women’s Medical University, Medical Center EastTokyoJapan
  2. 2.Department of Pharmacometrics and PharmacokineticsMeiji Pharmaceutical UniversityTokyoJapan

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