title: Active focal segmental glomerulosclerosis is associated with massive oxidation of plasma albumin.
abstract: The basic mechanism for idiopathic FSGS still is obscure. Indirect evidence in humans and generation of FSGS by oxidants in experimental models suggest a role of free radicals. In vitro studies demonstrate a main role of plasma albumin as antioxidant, its modification representing a chemical marker of oxidative stress. With the use of complementary liquid chromatography electron spray ionization tandem mass spectrometry (LC-ESI-MS/MS) and biochemical methods, plasma albumin was characterized in 34 patients with FSGS; 18 had received a renal transplant, and 17 had IgM mesangial deposition. Patients with FSGS that was in remission or without recurrence after transplantation had normal plasma albumin, and the same occurred in patients with primary and secondary nephrites and with chronic renal failure. In contrast, patients with active FSGS or with posttransplantation recurrence had oxidized plasma albumin. This finding was based on the characterization of albumin Cys 34 with an mass-to-charge ratio of 511.71 in triple charge that was consistent with the formation of a cysteic acid carrying a sulfonic group (alb-SO(3)(-)). The exact mass of albumin was increased accordingly (+48 Da) for incorporation of three oxygen radicals. Direct titration of the free sulfhydryl group 34 of plasma albumin and electrophoretic titration curves confirmed loss of free sulfhydryl group and formation of a fast-moving isoform in all cases with disease activity. This is the first demonstration of in vivo plasma albumin oxidation that was obtained with an adequate structural approach. Albumin oxidation seems to be specific for FSGS, suggesting some pathogenetic implications. Free radical involvement in FSGS may lead to specific therapeutic interventions.
authors.affiliation: Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Largo G. Gaslini, 5. 16148 Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Dimasi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Barbara
authors.initials: B
authors.lastname: Pavone
authors.forename: Piero
authors.initials: P
authors.lastname: Del Boccio
authors.forename: Monica
authors.initials: M
authors.lastname: Galliano
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002853:Chromatography, Liquid; D003545:Cysteine / Q000032:analysis; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D005978:Glutathione / Q000097:blood; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D009393:Nephritis / Q000378:metabolism*; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D017186:Titrimetry
chemical_list: D007075:Immunoglobulin M; D012709:Serum Albumin; D005978:Glutathione; D003545:Cysteine