Glomerular endothelium: a porous sieve and formidable barrier

Exp Cell Res. 2012 May 15;318(9):964-72. doi: 10.1016/j.yexcr.2012.02.032. Epub 2012 Mar 21.

Abstract

The glomerular capillary endothelium is highly specialized to support the selective filtration of massive volumes of plasma. Filtration is driven by Starling forces acting across the glomerular capillary wall, and depends on its large surface area and extremely high water permeability. Glomerular endothelial cells are extremely flat and perforated by dense arrays of trans-cellular pores, the fenestrae. This phenotype is critical for the high glomerular water permeability and depends on podocyte-derived VEGF, as well as TGF-beta. Endothelial cell-derived PDGFB, in turn, is necessary for the establishment of mesangial cells, which sculpt the glomerular loop structure that underlies the large filtration surface area. In pre-eclampsia, inhibition of the VEGF- and TGF-beta signaling pathways leads to endothelial swelling and loss of fenestrae, reducing the glomerular filtration rate. Similarly, in the thrombotic microangiopathies, glomerular endothelial cell injury coupled with inappropriate VWF activation leads to intracapillary platelet aggregation and loss of the flat, fenestrated phenotype, thus reducing the glomerular filtration rate. Normally, a remarkably small fraction of albumin and other large plasma proteins passes across the glomerular capillary wall despite the massive filtration of water and small solutes. An elaborate glycocalyx, which covers glomerular endothelial cells and their fenestrae forms an impressive barrier that, together with other components of the glomerular capillary wall, prevents loss of plasma proteins into the urine. Indeed, microalbuminuria is a marker for endothelial glycocalyx disruption, and most forms of glomerular endothelial cell injury including pre-eclampsia and thrombotic microangiopaties can cause proteinuria.

Publication types

  • Review

MeSH terms

  • Albuminuria / metabolism
  • Animals
  • Endothelium, Vascular / metabolism
  • Glomerular Filtration Rate
  • Humans
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / metabolism*
  • Permeability
  • Proteinuria / metabolism
  • Purpura, Thrombotic Thrombocytopenic / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta