title: Proteomics of plasma and urine in primary nephrotic syndrome in children.
abstract: Primary nephrotic syndrome in children, especially the variant with segmental glomerulosclerosis, remains an unsolved clinical problem. In spite of some progress, its pathogenesis is still unknown and the therapy options are confined to gross immune modulation. Indirect evidence based on posttransplant recurrence of the disease suggested an implication of plasma factors, whose characterization remains in course. Besides historical candidates, research is now considering glyco- and lipoderivatives. Structural analysis of plasma and urinary proteins based on proteomics has recently shown an increased proteolysis of major components such as albumin and the implication of alpha 1-antitrypsin that represents the first-line defense against exogenous and endogenous substances with proteolytic activity. Albumin has also emerged as a major plasma antioxidant, and recent studies have demonstrated that in patients with active focal segmental glomerulosclerosis albumin undergoes massive and stable oxidation with sulfonation of Cys34, formation of an adduct with +48 Da molecular weight, changes of the net charge due to additional negative residues, and loss of free thiol group (SH) titration. Altogether, these data suggest that oxidative stress determines selective protein damages in focal segmental glomerulosclerosis patients with formation of new adducts and fragmentation of plasma proteins. Research should now address whether oxidation of podocyte proteins is important for the maintenance of renal selectivity and is involved in proteinuria.
authors.affiliation: Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Laura
authors.initials: L
authors.lastname: Santucci
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Gusmano
authors.forename: Michele
authors.initials: M
authors.lastname: Carraro
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D002648:Child; D006801:Humans; D009404:Nephrotic Syndrome / Q000097:blood* / Q000652:urine*; D011507:Proteinuria / Q000097:blood* / Q000652:urine*; D040901:Proteomics / Q000639:trends*