What determines glomerular capillary permeability?

Abstract

There have been exciting recent advances in our understanding of the structural and molecular biology of the glomerular slit diaphragm, as described in a report in this issue of the JCI. These findings, combined with data on the permeability of the basement membrane and evidence that the endothelium may be a more important barrier than often supposed, are allowing a clearer understanding to emerge of how the 3 parts of the glomerular capillary wall jointly determine its functional properties.

Figure 1

Glomerular capillary wall, consisting principally of a fenestrated endothelium, a basement membrane, and epithelial foot processes. The foot processes form filtration slits spanned by slit diaphragms. Also shown is the endothelial cell coat, or glycocalyx. Some approximate dimensions are (8, 10): minimum diameter of fenestra, 30 nm; GBM thickness, 200–400 nm (depending on species); width of filtration slit, 40 nm. The glycocalyx thickness is uncertain. Figure is not drawn to scale.

Figure 2

Slit diaphragm structure proposed by Rodewald and Karnovsky (1). A central filament is connected to the podocyte membranes by alternating bridge fibers. The view is in the direction of filtrate flow. Figure reprinted with permission from the Proceedings of the National Academy of Sciences (17).