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Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study

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The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity.


We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer. Nephrotoxicity that developed within 14 days following CDDP administration was evaluated in accordance with Common Terminology Criteria for Adverse Events ver. 4.0 for acute kidney injury.


The rate of nephrotoxicity in patients with PPI (12%, n = 33) was significantly lower than that in patients without PPI (30%, n = 100). Severe nephrotoxicity greater than Grade 2 was not observed in patients with PPI, whereas the rate of hematological toxicity was comparable between patients with and without PPI. Kaplan–Meier analysis showed that the time to nephrotoxicity following CDDP administration was significantly prolonged in patients with PPI. Multivariate analysis revealed that co-administration of PPI with CDDP and 5-FU was an independent factor significantly contributing to the amelioration of nephrotoxicity (odds ratio 0.239, p = 0.033).


These findings indicate that co-administration of clinical doses of PPI could ameliorate nephrotoxicity without exacerbation of hematological toxicity in patients receiving CDDP and 5-FU therapy.

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This work was supported by a Grant-in-Aid for Scientific Research (C) [Grant 26460195 and 26460196] from the Japan Society for the Promotion of Science. We would like to thank Editage ( for English language editing.

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Correspondence to Masahiro Okuda.

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

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Ikemura, K., Oshima, K., Enokiya, T. et al. Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study. Cancer Chemother Pharmacol 79, 943–949 (2017).

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