The morphological basis of the glomerular permeability to proteins

The morphological basis of the glomerular permeability to proteins is reviewed and a survey is given of the studies done with ultrastructural tracer substances. In the normal GCW two structures have been considered important as a possible barrier to macromolecules: the GBM and the epithelial slit pore and slit diaphragm. The currently available evidence indicates that under normal conditions most plasma proteins do not penetrate beyond the subendothelial layer of the GCW. However, it is probable that the epithelial slit diaphragm acts as a secomdary barrier to macromolecules. In glomerular proteinurai the transport of anionic macromolecules through the GCW is increased, but the passage of uncharged macromolecules (PVP, dextran) is less than in the normal glomerulus. The number of anionic sites in the GCW is much smaller than in the normal glomerulus and there is a change in the normal arrangement of the foot processes and a decrease in the number of slit pores. At present, it is still incompletely understood in which way these changes are related to each other. Assuming the presence of focal leaks in the GCW, a possible sequence of events leading to glomerular proteinuria is discussed.