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Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model

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Abstract

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000 mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.

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Acknowledgments

The authors are grateful to Mr. Mitsuru Yokoyama, Shared-Use Research Center, University of Occupational and Environmental Health, for his technical assistance of electron microscopy.

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Authors and Affiliations

  1. Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Kei Yabuki, Yojiro Tsuda, Eisuke Shiba, Hiroshi Harada, Atsuji Matsuyama & Masanori Hisaoka

  2. Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Kei Yabuki & Keiji Hirata

  3. Division of Pathology, Saiseikai Yahata General Hospital, Kitakyushu, Japan

    Joji Haratake

  4. Department of Diagnostic Pathology, Japanese Red Cross Kochi Hospital, Kochi, Japan

    Kenji Yorita

  5. Department of Surgical Pathology, Kyushu Rosai Hospital, Kitakyushu, Japan

    Kazuyoshi Uchihashi

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  1. Kei Yabuki
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Correspondence to Kei Yabuki.

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Research Involving Human Participants and/or Animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study design involving humans was approved by the Ethics Committee of Medical Research, University of Occupational and Environmental Health, Japan (approval number H27-104). Informed opt-in/opt-out consent was obtained from all individual participants included in the study. All procedures performed in studies involving animals were in accordance with Guidelines for Proper Conduct of Animal Experiments by Science Council of Japan and approved by the Ethics Committee of Animal Care and Experimentation of the University of Occupational and Environmental Health, Japan (approval number AE15-011).

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Yabuki, K., Haratake, J., Tsuda, Y. et al. Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model. Biol Trace Elem Res 185, 36–47 (2018). https://doi.org/10.1007/s12011-017-1235-4

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