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Albumin oxidation leads to neutrophil activation in vitro and inaccurate measurement of serum albumin in patients with diabetic nephropathy.

Free Radic Biol Med. 2013 Feb 18;

Authors: Michelis R, Kristal B, Zeitun T, Shapiro G, Fridman Y, Geron R, Sela S


BACKGROUND: Previous studies suggest that oxidative modifications of serum albumin lead to underestimation of albumin concentrations using conventional assays. Secondly, oxidation of serum albumin may cause neutrophil activation and further oxidation of albumin, which may result in a series of reciprocal cyclical processes. Since hypoalbuminemia, systemic inflammation and oxidative stress are common in diabetic nephropathy patients, the aim of the present study was to show that albumin modifications and neutrophils activation underlie these reciprocal systemic processes. METHODS: Blood samples from a cohort of 19 patients with diabetic nephropathy and 15 healthy controls were used for albumin separation. An oxidation-dependent "albumin-detection index", representing the detection efficacy of the universal bromocresol-green (BCG) assay, was determined for each subject. This index was correlated with serum albumin levels, various markers of oxidative stress or inflammation and kidney function. Activation of separated neutrophils by glycoxidized-albumin was assessed by the release of neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). RESULTS: The albumin-detection index of diabetic nephropathy patients was significantly lower compared to controls, correlating positively with serum levels of albumin and kidney function, and negatively with albumin glycoxidation and inflammatory markers. Glycoxidized-albumin had a direct role in neutrophil activation, resulting in NGAL and MPO release. CONCLUSIONS: The hypoalbuminemia observed in patients with diabetic nephropathy partially results from underestimation of modified/oxidized albumin using the bromocresol-green assay. However, modified or oxidized albumin may lead to a cycle of accelerated oxidative stress and inflammation involving neutrophil activation. We imply that albumin detection index, a new marker of oxidative stress, may also serve as a biomarker of diabetic nephropathy severity and its progression.

PMID: 23429046 [PubMed - as supplied by publisher]