Proteomics of plasma and urine in primary nephrotic syndrome in children

被引:9
作者
Candiano, Giovanni [1 ]
Musante, Luca [1 ,3 ]
Petretto, Andrea [2 ]
Bruschi, Maurizio [1 ,3 ,5 ]
Santucci, Laura [1 ,3 ]
Urbani, Andrea
Scolari, Francesco [6 ]
Gusmano, Rosanna
Carraro, Michele [4 ]
Zennaro, Cristina [3 ]
Vincenti, Flavio [7 ]
Ghiggeri, Gian Marco [1 ]
机构
[1] G Gaslim Children Hosp, Lab Pathophysiol Uremia, IT-16148 Genoa, Italy
[2] G Gaslim Children Hosp, Mass Spectrometry Core Facil, IT-16148 Genoa, Italy
[3] Renal Child Fdn, Genoa, Italy
[4] Univ Trieste, Dept Nephrol, Trieste, Italy
[5] IRCCS Fdn Santa Lucia, Rome, Italy
[6] Univ Brescia, Dept Nephrol, Brescia, Italy
[7] Univ Calif San Francisco, Transplant Serv, San Francisco, CA 94143 USA
来源
PROTEOMICS IN NEPHROLOGY - TOWARDS CLINICAL APPLICATIONS | 2008年 / 160卷
关键词
D O I
10.1159/000125897
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 Cys(34), 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. Copyright (c) 2008 S. Karger AG, Basel.
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页码:17 / 28
页数:12
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