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Nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer

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Summary

We here report a case of nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer. A 68-year-old woman with recurrent gastric cancer developed acute kidney injury associated with kidney enlargement and urinary leukocytes after 38 cycles of nivolumab treatment. A diagnosis of acute granulomatous tubulointerstitial nephritis was made based on kidney biopsy findings. Immunohistochemistry revealed expression of programmed cell death–ligand 1 (PD-L1) in degenerated epithelial cells of collecting tubules. Among infiltrating immune cells, aggregation of T cells was more extensive than that of B cells, with CD4+ T cells outnumbering CD8+ T cells, consistent with the relative numbers of these cells in the circulation. Treatment with methylprednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function and reduction in the number of circulating CD4+ T cells. Prompt administration of high-dose corticosteroid is thus recommended after diagnosis of this adverse event of nivolumab treatment by kidney biopsy.

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Fig. 1: Computed tomography images of the kidneys
Fig. 2: [67Ga]Gallium citrate imaging performed 13 days after completion of the 38th cycle of nivolumab treatment
Fig. 3: Histopathology of kidney biopsy tissue
Fig. 4: Clinical course of the case

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Authors and Affiliations

  1. Department of Nephrology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Yoshihisa Nakatani, Masashi Ichikawa, Sachiyo Yamamoto, Akiko Mashiko & Shuji Arima

  2. Department of Clinical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Hisato Kawakami, Yasuo Otsuka & Kazuhiko Nakagawa

  3. Department of Pathology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Yasutoshi Takashima & Akihiko Ito

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  1. Yoshihisa Nakatani
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  2. Hisato Kawakami
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  3. Masashi Ichikawa
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  9. Kazuhiko Nakagawa
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Correspondence to Hisato Kawakami.

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Conflict of interest

Yoshihisa Nakatani declares that he has no conflict of interest. Hisato Kawakami has received honoraria from Ono Pharmaceutical Co. Ltd. Masashi Ichikawa declares that he has no conflict of interest. Sachiyo Yamamoto declares that she has no conflict of interest. Yasuo Otsuka declares that he has no conflict of interest. Akiko Mashiko declares that she has no conflict of interest. Yasutoshi Takashima declares that he has no conflict of interest. Akihiko Ito declares that he has no conflict of interest. Kazuhiko Nakagawa has received honoraria and research funding from Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co. as well as consulting fees from Ono Pharmaceutical Co. Ltd. Shuji Arima declares that he has no conflict of interest.

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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.

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Nakatani, Y., Kawakami, H., Ichikawa, M. et al. Nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer. Invest New Drugs 36, 726–731 (2018). https://doi.org/10.1007/s10637-018-0596-7

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  • DOI: https://doi.org/10.1007/s10637-018-0596-7

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