The podocyte as a target for therapies--new and old

Injury to the podocyte results in proteinuria and often leads to progressive kidney disease. As podocytes have limited ability to repair and/or regenerate, the extent of podocyte injury is a major prognostic determinant in diabetic nephropathy and other common causes of end-stage renal disease. Therapies aimed at preventing or limiting podocyte injury and/or at promoting podocyte repair or regeneration therefore have major potential clinical and economic benefits. Many current therapies--including glucocorticosteroids and calcineurin antagonists--have potent effects on podocytes. The nonspecific natures of these agents lead to undesirable systemic adverse effects: an agent with a more specific focus on podocytes would cause less treatment-associated morbidity. Recent years have seen dramatic advances in our understanding of podocyte biology and in particular regulation of its actin cytoskeleton, the major determinant of the complex architecture on which these cells depend for their function. This advance has allowed the identification of potential therapeutic targets and the next few years should see the development and testing of specific therapies aimed at the podocyte. Thus we are about to move from a situation where some of our 'blunderbuss' older therapies fortuitously happened to have beneficial effects on podocytes to a new era where advances in biological knowledge about a key cell type in the kidney will allow targeted drug design. As well as being intellectually more satisfying, every reason exists to believe that patients of the future will benefit and that the scourge of progressive kidney disease will be more effectively tackled.