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Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2023; 14(5): 460-480
Published online May 15, 2023. doi: 10.4239/wjd.v14.i5.460
Early diabetic kidney disease: Focus on the glycocalyx
Hui Yu, Yi-Yun Song, Xian-Hua Li
Hui Yu, Yi-Yun Song, Xian-Hua Li, Department of Nephrology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Yu H wrote the paper and collected the data; Song YY collected the data; Li XH was responsible for the design and guidance of the manuscript; and all authors have read and approve the final manuscript.
Supported by the Natural Science Foundation of Shandong Province of China, No. ZR2019MH072.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xian-Hua Li, MD, Professor, Department of Nephrology, Qilu Hospital of Shandong University, No. 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. lixianhua7075@sina.com
Received: December 7, 2022
Peer-review started: December 7, 2022
First decision: February 28, 2023
Revised: March 10, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 15, 2023
Processing time: 135 Days and 23.5 Hours
Abstract

The incidence of diabetic kidney disease (DKD) is sharply increasing worldwide. Microalbuminuria is the primary clinical marker used to identify DKD, and its initiating step in diabetes is glomerular endothelial cell dysfunction, particularly glycocalyx impairment. The glycocalyx found on the surface of glomerular endothelial cells, is a dynamic hydrated layer structure composed of pro-teoglycans, glycoproteins, and some adsorbed soluble components. It reinforces the negative charge barrier, transduces the shear stress, and mediates the interaction of blood corpuscles and podocytes with endothelial cells. In the high-glucose environment of diabetes, excessive reactive oxygen species and proinflammatory cytokines can damage the endothelial glycocalyx (EG) both directly and indirectly, which induces the production of microalbuminuria. Further research is required to elucidate the role of the podocyte glycocalyx, which may, together with endothelial cells, form a line of defense against albumin filtration. Interestingly, recent research has confirmed that the negative charge barrier function of the glycocalyx found in the glomerular basement membrane and its repulsion effect on albumin is limited. Therefore, to improve the early diagnosis and treatment of DKD, the potential mechanisms of EG degradation must be analyzed and more responsive and controllable targets must be explored. The content of this review will provide insights for future research.

Keywords: Glycocalyx; Diabetic kidney disease; Endothelial cells; Reactive oxygen species; Microalbuminuria; Enzyme

Core Tip: In the diabetic microenvironment, various harmful factors, such as oxidative stress and inflammation, contribute to endothelial glycocalyx (EG) disruption through direct damage to the glycocalyx or indirect degradation due to the upregulation of related sheddases. Shedding one or more components after damage to the EG is an early sign of numerous pathological states, including diabetes. The loss of filtration barrier integrity can lead to microalbuminuria, which is predictive of diabetic kidney disease (DKD). Identifying and targeting the key molecules involved in glycocalyx damage thus represent current hot topics in DKD research.