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Reduction of endothelial glycocalyx on peritubular capillaries in chronic kidney disease

  • Author Footnotes
    ∗ These authors contributed equally to this work
    Katja Ermert
    Footnotes
    ∗ These authors contributed equally to this work
    Affiliations
    Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany

    Division of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany
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  • Author Footnotes
    ∗ These authors contributed equally to this work
    Eva Miriam Buhl
    Footnotes
    ∗ These authors contributed equally to this work
    Affiliations
    Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany

    Division of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany

    Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany
    Search for articles by this author
  • Barbara Mara Klinkhammer
    Affiliations
    Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany

    Division of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany
    Search for articles by this author
  • Jürgen Floege
    Affiliations
    Division of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany
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  • Peter Boor
    Correspondence
    Address correspondence to: Peter Boor, MD, PhD, Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany, Phone: +49 241 80 85227, Fax: +49 241 80 82446.
    Affiliations
    Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany

    Division of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany

    Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany
    Search for articles by this author
  • Author Footnotes
    ∗ These authors contributed equally to this work
Published:November 19, 2022DOI:https://doi.org/10.1016/j.ajpath.2022.11.003

      ABSTRACT

      In chronic kidney disease, peritubular capillaries undergo anatomical and functional alterations such as rarefaction and increased permeability. The endothelial glycocalyx is a carbohydrate-rich gel-like mesh, which covers the luminal surface of endothelial cells. It is involved in many regulatory functions of the endothelium, including vascular permeability. Here, we investigated ultrastructural alterations of the endothelial glycocalyx in different murine chronic kidney disease models. Fluorescence stainings using different lectins with high affinity to components of the renal glycocalyx revealed a reduced binding to the endothelium in chronic kidney disease in the animal models, and similar finding in human kidney specimens. We used the Lanthanum Dysprosium Glycosamino Glycan adhesion staining technique to visualize the ultrastructure of the glycocalyx in transmission electron microscopy. This also enabled quantitative analyses, showing a significant reduction of the endothelial glycocalyx thickness and density. Additionally, mRNA expression of proteins involved in glycocalyx biology, synthesis and turnover, i.e., syndecan 1 and glypican 1, which are main components of the glycocalyx, and exostosin 2, involved in the synthesis of the glycocalyx, were significantly upregulated in endothelial cells isolated from murine chronic kidney disease models.
      Visualization of glycocalyx using specific transmission electron microscopy analyses allows qualitative and quantitative analyses and revealed significant pathological alterations in peritubular capillaries in chronic kidney disease.

      KEYWORDS

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