Early diabetic kidney disease: Focus on the glycocalyx

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.