Structure of the glomerular filtration barrier and its alterations

The discovery of nephrin and other proteins of the slit diaphragm (SD) has widened our knowledge of the glomerular filtration barrier. Little was known about the biology of podocytes. Recent data has allowed us to understand more about this continuous interdigitated membrane along the foot processes (FP), known as SD, that penetrates the filtration space between podocytes, with the properties of adherent unions fixed to the actin citoskeleton of the podocytes. The regulatory framework of the proteins in the SD is complex; they are highly specialized and dynamic; the most important proteins in the SD are Nephrin and Neph 1. They contribute to the restriction pores of the filtration barrier. They produce cytosolic signals, and with other molecules and a number of adaptor proteins, they contribute to the survival, polarity and endocytosis of podocytes. Mutations in the proteins of the SD interfere with signal transduction in podocytes altering their normal architecture, functional integrity and survival, producing primary and secondary nephropathies, proteinuria, glomerulosclerosis and progression to end stage renal disease.