2.1.1. Podocytes

Podocytes are terminally differentiated cells that have three distinct compartments: the cell body, primary processes, and foot processes. Foot processes from adjacent podocytes are connected by a slit diaphragm, which forms the most selective component of the

glomerular filtration barrier. Hyperfiltration causes foot processes and the slit diagram to be exposed to high tensile and fluid flow shear stress, which can cause stretching, injury, and loss of barrier function [14,15]. The changes in hemodynamic forces within the glomerulus modify the actin cytoskeleton of podocyte foot process, which can lead to effacement and disruption of the filtration barrier [16–20]. If hyperfiltration is not corrected, podocytes may detach, which leads to podocyturia, proteinuria, and decreases in GFR. Detachment is irreversible and often leads to glomerulosclerosis and CKD [21]. Studies in mice have found that vascular endothelial growth factor (VEGF)-A is required in developing podocytes to establish and maintain the glomerular filtration barrier [22]. In addition, the soluble VEGF receptor 1 (sFlt-1) appears to play a role in endothelial dysfunction observed in CKD [23]. Loss of VEGF-A can lead to dysregulation of podocytes, loss of endothelial cells, and collapse of glomerular capillaries [22].
