Reduction of Endothelial Glycocalyx on Peritubular Capillaries in Chronic Kidney Disease

Abstract

In chronic kidney disease (CKD), peritubular capillaries undergo anatomic and functional alterations, such as rarefaction and increased permeability. The endothelial glycocalyx (EG) 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. Herein, we investigated ultrastructural alterations of the EG in different murine CKD models. Fluorescence staining using different lectins with high affinity to components of the renal glycocalyx revealed a reduced binding to the endothelium in CKD in the animal models, and there were 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 EG thickness and density. In addition, mRNA expression of proteins involved in glycocalyx biology, synthesis, and turnover (ie, syndecan 1 and glypican 1), which are main components of the glycocalyx, and exostosin 2, involved in the synthesis of the glycocalyx, were significantly up-regulated in endothelial cells isolated from murine CKD models. Visualization of glycocalyx using specific transmission electron microscopy analyses allows qualitative and quantitative analyses and revealed significant pathologic alterations in peritubular capillaries in CKD.