title: Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration.
abstract: Chronic proteinuric renal diseases, independent from the type of the initial insult, have in common a loss of selectivity of the glomerular barrier to protein filtration. Glomerular sclerosis is the progressive lesion affecting the glomerular capillary wall, the primary site at which the protein filtration is abnormally enhanced by disease. Dysfunction of podocytes, that serve to maintain the intact barrier, is a central event in lesion development. However, glomerular injury is signalled to tubular and interstitial structures largely in advance of nephron destruction. Glomerular ultrafiltration of excessive amounts of plasma-derived proteins and associated factors incites tubulointerstitial damage and might amplify an inherent susceptibility of the kidney to become dysfunctional in several disease conditions. Thus, noxious substances in the proteinuric ultrafiltrate promote apoptotic responses and multiple changes in the phenotype of tubule cells with generation of inflammatory and fibrogenic mediators. The severity of tubular interstitial damage has long been recognized to be highly correlated to the degree of deterioration of renal failure even better than glomerular lesions. This review focuses on pathways of tubular injury and apoptosis that in turn promote nephron-by-nephron degeneration and interstitial fibrosis during proteinuria contributing to multifaceted processes of kidney scarring and function loss.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D003165:Complement System Proteins / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D009395:Nephritis, Interstitial / Q000503:physiopathology; D009399:Nephrons / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D051437:Renal Insufficiency / Q000378:metabolism; D012598:Sclerosis / Q000503:physiopathology*
chemical_list: D003165:Complement System Proteins
keywords: apoptosis; inflammation; proteinuria; tubule cell damage