Open AccessRepetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome
Author(s) -
Giovanni Candiano,
Luca Musante,
Maurizio Bruschi,
Andrea Petretto,
Laura Santucci,
Piero Del Boccio,
Barbara Pavone,
Francesco Perfumo,
Andrea Urbani,
Francesco Scolari,
Gian Marco Ghiggeri
Publication year - 2006
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2006050486
Subject(s) - nephrotic syndrome , albumin , proteinuria , chemistry , medicine , fragmentation (computing) , blood proteins , urinary system , urine , endocrinology , kidney , biochemistry , biology , ecology
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.