Mechanisms and significance of proteinuria

Summary: Glomerular permselectivity is determined by complex interactions of the glomerular basement membrane (GBM) and the endothelial and epithelial cells of the glomerular capillary wall. Proteinuria may result acutely from functional changes in filtration, and be quickly reversible. Chronic structural changes may also contribute to proteinuria in many disease settings by affecting the components of the glomerular capillary wall (GCW). Thus, glomerular epithelial cell abnormalities are prominent in both minimal change disease and focal segmental glomerulosclerosis, whereas altered GBM thickness and composition are major features in diabetic nephropathy and Alport syndrome. A multitude of pathologic stimuli appear to influence proteinuria, including the renin‐angiotensin system and numerous other cytokines. Human and experimental data indicate a heterogeneity of mechanisms in different diseases manifesting proteinuria which are associated with a range of structural appearances from normal morphology to a severely damaged GCW. Current therapeutic trials in progressive human renal diseases have focused on the potential benefits of angiotensin converting enzyme inhibitor (ACEI). Encouraging results indicate amelioration of both functional and structural components of proteinuria, as well as a benefit on sclerosis, although the latter effect has so far only been documented in animal studies. Advances in molecular technologies may allow identification of more specific abnormalities in the GCW which underlie proteinuria. Further understanding of these abnormalities will direct future therapy at the specific defect in each disease setting.