Novel concepts in understanding and management of glomerular proteinuria

Abstract

‘Form follows function’ and ‘time is precious’: these principles are conflated in the glomerular podocyte. They define its function but also the necessity to limit the exposure of podocytes to injurious agents. A number of glomerular disorders that may lead to chronic kidney disease are characterized by simplification and retraction of podocyte foot processes (FP) (effacement). These structural podocyte defects are highly reversible for a certain time and every effort should be undertaken to prevent disease progression and the need for renal replacement therapy, which harbors enormous financial and human costs. Podocytes elaborate a network of processes—major processes and FP, which surround glomerular capillaries. Together with the glomerular basement membrane (GBM) and the glomerular endothelial cells, podocytes provide the structural basis for glomerular filtration w1x. Although it is generally acknowledged that the GBM can restrict the passage of large plasma proteins, there is increasing evidence that the ultimate barrier for proteins larger than albumin is the slit diaphragm (SD). The past 4 years have been extremely fruitful in providing an extensive amount of information on the molecular composition of the SD, and opened up new avenues to understand podocyte function w2,3x. ACE inhibitors and angiotensin receptor blockers have proven effective in ameliorating glomerular proteinuria and slowing of disease progression in proteinuric renal diseases and in diabetic nephropathy in particular w4–8x. In addition, there are novel intriguing experimental data that link the salutary effects of these drugs to changes in the composition of the SD. This comment is focused on the recent progress in understanding the molecular mechanisms that underlie SD dysfunction and the development of proteinuria.