Podocyte biology for the bedside

Abstract

The explosion of podocyte biology during the last decade has radically altered our views on the pathophysiologic process of proteinuria, glomerular disease, and progressive kidney disease. In this review, we highlight some of these landmark findings, but focus on recent advances in the field and implications for translating this biology into therapy for podocyte diseases.

Figure 1

Glomerular capillary wall. This acts as the glomerular filtration barrier preventing proteins and large molecules from passing from the capillary lumen into the urinary space. The podocyte cell body lies with the urinary space, and the cell is attached to the GBM via the foot process. Adjacent foot processes are separated by the filtration slit, bridged by the slit diaphragm. Disruption of the glomerular filtration barrier leads to proteinuria.

Figure 2

Podocyte and glomerular capillary. Electron micrograph showing glomerular capillary loops, one containing a red blood cell (RBC), with the glomerular basement membrane (GBM) lined by the glomerular endothelial cell (GEN) and the podocyte cell body (Podo) lying in the urinary space extending foot processes (FP) to the outer surface of two adjacent capillary loops.

Figure 3

Foot processes and slit diaphragm. The podocyte has a prominent actin cytoskeleton, stabilized by synaptopodin and α-actinin-4, and linked to the slit diaphragm via CD2AP. The foot processes are bound to the glomerular basement membrane via integrins (α3β1, αVβ3) and α- and β-dystroglycans (DG). The major component of the slit diaphragm is nephrin, which bridges the filtration slit and is closely associated with several other proteins including podocin and CD2AP.