Active focal segmental glomerulosclerosis is associated with massive oxidation of plasma albumin.

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-SO3-). 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.