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.