The podocyte: a potential therapeutic target in diabetic nephropathy?

Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways. loss of the alpha(3)beta(1)integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumutation of abnormal extracellular matrix, apoplosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function, Some currently used therapies, such as tight glucose control a inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific and in podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.