The role of the glomerular endothelium in albumin handling

The unique permeability characteristics of the glomerular capillary wall depend on its three-layer structure, consisting of endothelial cells, the basement membrane and podocytes. These components form the glomerular filtration barrier (GFB). That albuminuria may occur in the absence of changes in podocyte foot processes suggests that GFB components other than podocytes have essential roles in albumin handling. The endothelium forms the first part of the GFB and is characterized by fenestrations-transcellular holes that are filled with endothelial glycocalyx, a hydrated mesh principally comprised of proteoglycans. The glycocalyx and adsorbed plasma constituents form the endothelial surface layer (ESL). Human and animal studies have shown that the glomerular ESL restricts macromolecule passage and ensures that plasma albumin is largely excluded from the GFB. The glomerular endothelium is also likely to indirectly influence glomerular albumin handling by modifying podocyte behaviour. These modifications may occur physiologically through soluble mediators and/or pathologically through increased exposure of podocytes to plasma components as a consequence of ESL dysfunction. The importance of the glomerular endothelium and ESL in albumin handling also sheds light on the relationship between albuminuria and vascular disease. The therapeutic potential that this relationship offers will become evident with better understanding of the structure, composition and regulation of the glycocalyx.