The Glomerular Filtration Barrier: Components and Crosstalk

Abstract

The glomerular filtration barrier is a highly specialized blood filtration interface that displays a high conductance to small and midsized solutes in plasma but retains relative impermeability to macromolecules. Its integrity is maintained by physicochemical and signalling interplay among its three core constituents—the glomerular endothelial cell, the basement membrane and visceral epithelial cell (podocyte). Understanding the pathomechanisms of inherited and acquired human diseases as well as experimental injury models of this barrier have helped to unravel this interdependence. Key among the consequences of interference with the integrity of the glomerular filtration barrier is the appearance of significant amounts of proteins in the urine. Proteinuria correlates with kidney disease progression and cardiovascular mortality. With specific reference to proteinuria in human and animal disease phenotypes, the following review explores the roles of the endothelial cell, glomerular basement membrane, and the podocyte and attempts to highlight examples of essential crosstalk within this barrier.

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

“…For example, inflammatory cytokines or fibrogenic mediators had been shown to modulate podocyte motility and albumin permeability, mRNA expression of podocyte markers such as nephrin and ezrin as well as podocyte survival and adhesion (9)(10)(11)(12)(13)(14)(15). Presumably, through mesangial cellpodocyte communication (16)(17)(18), these effects might lead to breakdown of the glomerular permeability with resultant formation of proteinuria.…”

“…And mesangialderived cytokines such as tumor necrosis factor (TNF)-α or transforming growth factor (TGF)-β1 can inhibit the expression of nephrin and ezrin by podocytes and induce podocyte death and detachment (14,15). These observations imply the existence of a potential mesangial cellpodocyte crosstalk (16)(17)(18), and raise the possibility that certain cytokines produced by activated mesangial cells in anti-Thy1 glomerulonephritis may act in a paracrine manner on adjacent podocytes, which then cause proteinuria via alterations of glomerular permselectivity. The objective of this study was to investigate…”

A Case Report of Atypical Hemolytic Uremic Syndrome Presenting with Massive Proteinuria

“…Some explanations are that it is due to a complementmediated injury to the glomerular filtration barrier [8], podocyte dysfunction via mutations in diacylglycerol kinase ε (DGKE) [9], and disruption of vascular endothelial growth factor function [10]. Nevertheless, proteinuria is a parameter that has been studied as a function of recovery in children affected with hemolytic uremic syndrome.…”

Effects of UVC Radiation on the Thickness of Glomerular Basement Membrane in Mole Rats

“…The GBM is the main portion of the Glomerular Filtration Barrier (GBF) that borders the capillary lumen and urinary space (Arkill et al, 2014;Menon et al, 2012). The glomerular filter, through which the infiltration passes, consists of three layers: fenestrated endothelium, intervening GBM and the podocytes layer (Menon et al, 2012;Shirato et al, 1991).…”

“…The glomerular filter, through which the infiltration passes, consists of three layers: fenestrated endothelium, intervening GBM and the podocytes layer (Menon et al, 2012;Shirato et al, 1991). This complex membrane is permeable to water and small solutes, but retains most of the proteins and other large molecules as well as whole blood cells (Farquhar, 1991;Solak, 2010).…”