Changes in glomerular perm-selectivity induced by angiotensin II imply podocyte dysfunction and slit diaphragm protein rearrangement.

Molecular mechanisms governing the loss of glomerular membrane perm selectivity during progression of proteinuric kidney diseases are so far poorly defined. Discovery of the proteins of the podocyte slit diaphragm, including the nephrin-CD2AP-podocin complex, has represented a major breakthrough in understanding the crucial role of the glomerular epithelial layer in the pathogenesis of proteinuria in human congenital disorders. A number of studies have tried to address the role of nephrin in acquired proteinuric disorders with conflicting results. In human diabetic nephropathy a defect of nephrin gene and protein expression has been consistently reported, which translates in profound changes of filtration slit ultrastructural architecture. The exclusive effect of angiotensin II inhibitors of restoring deficient nephrin expression in proteinuric diseases underlines a close interaction between angiotensin II and podocyte proteins and indicates a fresh way to look at the renoprotective properties of these molecules.