title: Role of increased glomerular protein traffic in the progression of renal failure.
abstract: Clinical and experimental data have indicated that heavy proteinuria in renal glomerular diseases is associated with the formation of tubulointerstitial fibrosis and contributes to the progression of renal failure. In recent years studies have focused on the possibility that albumin and other proteins that accumulate in the lumen of proximal tubular cells as a consequence of glomerular permeability dysfunction, are a direct cause of tubular cell injury. Specific proteins that have been shown to be cytotoxic are transferrin/iron, lipoproteins and complement components, all of which appear in the urine in proteinuric states. As an additional pathway of injury one may consider the effects of lipids bound to albumin and lipoproteins, including oxidized low density lipoproteins, which, by inducing an oxidative stress to tubular cells, are potent cytotoxic molecules. Moreover, reabsorption of high molecular weight proteins activates proximal tubular cells to produce matrix proteins, cytokines, chemoattractants and vasoactive mediators that may-converge in stimulating interstitial inflammation and scarring. Given the functional toxicity of filtered proteins on the kidney, pharmacological and dietary manipulations aimed at reducing glomerular protein traffic may have a beneficial impact on the deterioration of renal function in progressive nephropathies.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Bruzzi
authors.forename: A
authors.initials: A
authors.lastname: Benigni
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D011507:Proteinuria / Q000378:metabolism / Q000503:physiopathology*