Molecular basis of glomerular permselectivity

Recent discoveries in kidney research have given new insights into the mole cular make-up of the glomerular filter and mechanisms of permselectivity. T he identification of mutations in the genes for glomerular basement membran e type IV collagen has thus demonstrated the central role of the glomerular basement membrane as the structural skeleton of the glomerular capillary. Regional deterioration of this framework not only leads to proteinuria, but also to significant leakage of red blood cells into the urinary space. Tra cer studies and the characaterization of other glomerular basement membrane components, such as proteoglycans, have also emphasized the role of the gl omerular basement membrane in the permselectivity process. However, more re cent studies on nephrin, a key component of the slit diaphragm, as well as the podocyte and slit diaphragm-associated intracellular proteins, CD2-asso ciated protein, podocin and alpha -actinin-4, have emphasized the role of t he slit diaphragm as a central size-selective filtration barrier. These dat a have provided a completely new understanding of the mechanisms of protein uria, both in inherited and acquired diseases. In this review, we present t he recent progress made in the characterization of proteins that are import ant for glomerular permselectivity. Curr Opin Nephrol Hypertens 10:543-549. (C) 2001 Lippincott Williams & Wilkins.