Glomerular protein trafficking and progression of renal disease to terminal uremia.

Experimental and human studies indicate that altered glomerular permeability to proteins correlates with tubulointerstitial injury and subsequent glomerular scarring. Maneuvers that restore the selectivity of glomerular barrier to macromolecules limit renal injury in progressive nephropathies. The abnormal traffic of proteins through the glomerular capillary has an intrinsic renal toxicity linked to the process of over-reabsorption by proximal tubular cells. Excessive protein reabsorption induces functional alterations of tubular cells that overexpress inflammatory and vasoactive molecules, as indicated by in vitro or in vivo studies. Thus monocyte chemoattractant protein-1 and osteopontin may attract inflammatory cells into renal interstitium. Enhanced tubular endothelin-1 secretion, mainly toward the basolateral membrane of the cell, may stimulate interstitial macrophage infiltration and in addition may promote interstitial fibroblast proliferation and extracellular matrix synthesis, thus amplifying tubulointerstitial inflammation and injury.