title: Repetitive fragmentation products of albumin and alpha1-antitrypsin in glomerular diseases associated with nephrotic syndrome.
abstract: Even if nephrotic syndrome is characterized by massive urinary loss of major plasma proteins, a clear structural characterization based on proteomics has never been reported. Urine and plasma of 23 patients with different idiopathic nephrotic syndromes (10 steroid-sensitive minimal-change nephropathy, seven steroid-resistant FSGS, and six membranous glomerulonephritis) were analyzed with two-dimensional electrophoresis in soft gel, Western blot, and matrix-assisted laser desorption/ionization time of flight mass spectrometry; 72 urinary components corresponded to fragments of albumin and/or of alpha1-antitrypsin. Several repetitive fragmentation motives and a few differences among different pathologies were found. Several (21 of 72) urinary albumin fragments also were detected in plasma, although in lower concentration, suggesting a preferential excretion. The bulk of components with low molecular weight were detected only in urine, suggesting an in situ formation; zymograms with albumin as substrate showed the presence in urine of specific proteases. A final but not secondary point was the characterization of albumin adducts that harbor both the COOH and NH2 terminal parts of the protein, suggesting the formation of new covalent chemical groups. Altogether, these new findings reveal unexpected structural and functional aspects of proteinuria that may play a key role in pathogenesis. Characterization of urinary fragmentation patterns should be extended to other renal diseases.
authors.affiliation: Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Laura
authors.initials: L
authors.lastname: Santucci
authors.forename: Piero
authors.initials: P
authors.lastname: Del Boccio
authors.forename: Barbara
authors.initials: B
authors.lastname: Pavone
authors.forename: Francesco
authors.initials: F
authors.lastname: Perfumo
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism*; D002648:Child; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D000418:Albumins; D000515:alpha 1-Antitrypsin