The glomerular endothelial glycocalyx as a therapeutic target in proteinuric kidney disease

Abstract

Endothelial glycocalyx lines every blood vessel throughout the body, and has key roles in vascular biology, including vascular permeability and inflammation. Accumulated evidence from the past 15 years shows that the glomerular endothelial glycocalyx is a vital component of the glomerular filtration barrier, which limits the filtration of macromolecules such as albumin. However, the contribution of endothelial glycocalyx to the pathogenesis of proteinuria and its potential as a therapeutic target have not been fully explored. Experimental disruption of the glomerular endothelial glycocalyx increases glomerular albumin permeability, and loss of endothelial glycocalyx integrity has been observed in diseases that compromise the glomerular filtration barrier, including diabetic kidney disease and other glomerular diseases. Strategies to protect the endothelial glycocalyx have successfully reduced proteinuria in animal models of proteinuric kidney disease, indicating that therapeutic modification of the endothelial glycocalyx can achieve important functional benefits. Moreover, drugs with recognized roles in renal medicine (for example, mineralocorticoid receptor antagonists) reduce albuminuria at least in part by protecting the endothelial glycocalyx. Recognition of the glomerular endothelial glycocalyx as a therapeutic target could aid the development of drugs that specifically target the endothelial glycocalyx with potentially greater benefits than those that do so incidentally.