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

Previous studies suggest that oxidative modifications of serum albumin lead to underestimation of albumin concentrations using conventional assays. In addition, oxidation of serum albumin may cause neutrophil activation and further oxidation of albumin, which may result in a series of reciprocal cyclical processes. Because hypoalbuminemia, systemic inflammation, and oxidative stress are common in diabetic nephropathy patients, the aim of this study was to show that albumin modifications and neutrophil activation underlie these reciprocal systemic processes. 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 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). The albumin detection index of diabetic nephropathy patients was significantly lower compared to that of 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. 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 suggest that the albumin detection index, a new marker of oxidative stress, may also serve as a biomarker of diabetic nephropathy severity and its progression. (C) 2013 Elsevier Inc. All rights reserved.