New insights into the role of podocytes in proteinuria.

Disturbances in many different molecular pathways and interactions can lead to the same clinical end points of proteinuria and end-stage renal disease. Proteinuria is often accompanied by a cytopathological change in the glomerulus that is referred to as effacement (retraction) of the podocyte foot processes. The molecular mechanisms that lead to proteinuria and podocyte effacement are poorly understood; therefore, targeted therapies are lacking. During the past 5 years, however, a large body of data has emerged in this field. The discovery of podocyte gene defects that underlie some hereditary proteinuric syndromes has changed our understanding of the relative contributions of components of the glomerular filter. Furthermore, pathogenic pathways activated in podocytes during proteinuria have been identified. Together, these findings pinpoint the podocyte as the most obvious candidate for therapeutic intervention. In the near future, the use of large-scale expression profiling platforms, transgenic mouse lines, and other in vivo gene delivery methods will further expand our understanding of the pathology of the glomerular filtration barrier, and perhaps reveal novel target molecules for the therapy of proteinuric kidney diseases.