Redox state of urinary albumin in patients with IgA nephropathy.

ABSTRACT

We examined the relationship between oxidative damage and molecular instability of urinary albumin in the urine of patients with IgA nephropathy (IgAN). As measure of oxidation, we detected the free thiol group at Cys34 in albumin (albumin-Cys34) using maleimide-PEG2-biotin reagent; because decreased levels of albumin-Cys34 are correlated with increased oxidation. The urine albumin-Cys34 level in all 30 patients with IgAN was decreased to varying extents. No correlations were found between urinary albumin/creatinine ratio and decreased urinary albumin-Cys34 level. Furthermore, decreases in urinary albumin-Cys34 were not accompanied by changes in serum albumin-Cys34. In diagonal-two-dimensional SDS PAGE analysis which reveals reduction-induced degradation of H2O2-treated human serum albumin, a similar pattern of albumin degradation was also detected in urine samples from patients with IgAN, indicating that structural alterations resulting from oxidative stress may be involved. Our findings suggest that redox state, in addition to urinary albumin concentration, may be an important indicator of post-translational modification and a potentially useful predictor of the kidney disease.