Vascular Endothelial Growth Factor and Diabetic Nephropathy

The field of vascular endothelial growth factor (VEGF) has recently witnessed a surge of research into its role in diabetic kidney disease. Based on its credentials as a potent inducer of vasopermeability and angiogenesis, podocyte-derived VEGF is believed to participate in the glomerular capillary hyperpermeability of macromolecules that potentially underlies the pathogenesis of diabetic albuminuria. The evidence for VEGF's role is relatively straightforward in animal models of diabetes, establishing that VEGF is upregulated in the diabetic kidney, that VEGF alone reproduces some aspects of diabetic glomerulopathy, and that antagonism of VEGF attenuates diabetic albuminuria and other associated features of the podocytopathy. However, the promise shown in the animal studies has not carried over as convincingly into the realm of human studies, as some investigators find a negative or no relationship between VEGF and diabetic nephropathy, whereas others find a positive correlation between the two. If VEGF does play a role in diabetic renal disease, its observed effects and known mechanisms seem to point squarely at the podocyte as a central target of the maladaptive VEGF overactivity.