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Nivolumab-associated glomerular endothelial injury in a patient with gastric cancer

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Abstract

A 68-year-old male with gastric cancer was treated with tegafur/gimeracil/oteracil and oxaliplatin for 6 months. Thereafter, he was treated with paclitaxel and ramucirumab for 3 months. However, neither regimen had much effect. Thus, he was treated with nivolumab for 2 months, but he developed proteinuria, microhematuria, and an acute kidney injury. A kidney biopsy revealed occasional swollen endothelial cells and proliferating mesangial cells. Few abnormal findings were seen in the tubules or interstitial tissue. Immunofluorescent staining showed segmental immunoglobulin A and complement component 3 deposition, in the mesangial area. Electron microscopy showed a small amount of electron-dense deposits in the paramesangial area and swollen endothelial cells. Mesangial interposition, the loss of endothelial cell fenestration, and subendothelial edema were also observed. Furthermore, foot process effacement and villous transformation of epithelial cells were noted. After the discontinuation of nivolumab, the patient’s renal function gradually improved, and his proteinuria disappeared. Nivolumab treatment was restarted at that time because of cancer progression; however, it was ineffective. No occult blood was detected from 7 months after the administration of the last dose of nivolumab. This is a unique case, in which a kidney biopsy revealed evidence of nivolumab-associated glomerular endothelial injury.

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Correspondence to Kensei Yahata.

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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 at which the studies were conducted and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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13730_2021_610_MOESM1_ESM.png

Supplementary Fig. 1 Immunohistochemistry performed with PD-L1 antibodies. a: PD-L1 staining of the tubular epithelial cell membrane (PNG 902 kb)

b: Negative control for the examination shown in Supplementary Fig. 1a (PNG 890 kb)

c: PD-L1 staining of inflammatory cells (PNG 846 kb)

d: Negative control for the examination shown in Supplementary Fig. 1c (PNG 850 kb)

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Shim, J., Tochio, A., Ueda, N. et al. Nivolumab-associated glomerular endothelial injury in a patient with gastric cancer. CEN Case Rep 10, 576–581 (2021). https://doi.org/10.1007/s13730-021-00610-0

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  • DOI: https://doi.org/10.1007/s13730-021-00610-0

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