The limited role of the glomerular endothelial cell glycocalyx as a barrier to transglomerular albumin transport

Abstract

For over 50 years, the glomerular filter has been thought to exert an uniquely significant barrier to the transport of albumin. The glomerular endothelial cell glycocalyx is considered to contribute to this important barrier restriction. In renal disease, structural alterations to this layer have been associated with albuminuria. It appears however the claims of the influence of this barrier have been overstated. The behaviour of albumin in systems that model the glycocalyx has been studied widely and the results demonstrate that the endothelial glycocalyx would offer only relatively small effective barrier to albumin. This has been confirmed in studies on macromolecular exchange in non-renal capillary beds with similar endothelial glycocalyx. The experimental perturbations to the glomerular endothelial glycocalyx (through enzyme treatments, saline washouts) also create only relatively small changes in the level of albuminuria as compared to changes in albumin excretion seen in renal disease and nephrotic states. Additionally, it is questionable how specific these perturbations are. Overall, the endothelial glycocalyx most likely has biological functions like it does in other extracellular regions involving hydration through osmotic pressure and offering charge-mediated binding of various molecules. This confirms work by Comper and colleagues that the glomerular sieving of albumin is not unique and is consistent with that of size selectivity that results in significant amounts of albumin being filtered normally, retrieved by proximal tubules and returned to the blood supply.