New aspects of glomerular filtration barrier structure and function: five layers (at least) not three

Three structures (glomerular endothelial fenestrae, glomerular basement membrane and podocyte interfoot process/slit diaphragms) have traditionally been considered as the major determinants of glomerular permeability. We review recent work demonstrating the functional importance of two additional layers: the endothelial surface layer (ESL) and the subpodocyte space (SPS).

Removing glomerular endothelial cell monolayer ESL in vitro significantly alters monolayer permeability, supporting previous in-vivo demonstrations of the importance of the ESL in determining glomerular permeability. Whether fenestral diaphragms are present to support the ESL in healthy adult glomeruli has been examined in a recent report. On the downstream side of the glomerular filtration barrier, the SPS is a recently described structure that covers approximately two-thirds of the barrier, has highly restrictive dimensions and contributes to the hydraulic resistance and ultrafiltration characteristics of the glomerulus. Different layers of the barrier have also been shown to influence the permeability characteristics of one another, either through biophysical interactions, or through the activities of ligand-receptor axes that cross the various layers of the barrier.

The structure and function of the glomerular filtration barrier remains an area of significant new discovery, and recent work continues to highlight the complexity of this dynamic multilayered watershed.