Regulation of glomerular permeability by VEGF

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End stage kidney failure is becoming increasingly common across the developed world - averaging a 5% increase per year in the UK. The 37,500 UK patients with end stage kidney disease represent a significant financial burden, representing 3% of the entire health budget consumed by 0.06% of the population. Many kidney diseases stem from injury to the kidney filters or glomeruli. In health these filtering units are very permeable to water and small molecules (promoting the production of urine) but have a low permeability to proteins (which are important molecules to conserve). Thus the filters have a differential permeability to different substances. Many kidney diseases are characterised by a derangement in permeability and leakage of protein into the urine. Furthermore, for reasons that are not clear, the presence of protein in the urine has also recently been identified as a very strong predictor of cardiovascular disease (stokes, heart attacks etc). The glomeruli contains cells (podocytes) that produce molecules such as Vascular Endothelial Growth Factors (VEGF) that regulate glomerular function. We intend to study the effects of two forms of VEGF - VEGF165 and VEGF165b in models of disease in which expression of these molecules may be controlled. Furthermore, since structure predicts function, we will reconstruct these glomeruli in 3D at the electron microscope level. This study may allow the development of novel strategies to maintain normal or re-establish normal permeability. This may therefore have profound implications not only for kidney patients but also those at risk of cardiovascular disease producing significant financial benefits for health service providers.