Oxidative modifications impair albumin quantification.

BACKGROUND: Hypoalbuminemia is a measure of malnutrition, inflammation and a predictor of mortality in uremia. It is controversial whether albumin levels per se are associated with the clinical outcomes in uremic patients. The co-occurrence of hypoalbuminemia and oxidative stress in hemodialysis (HD) patients led us to hypothesize that oxidative modifications of albumin decrease its detection and influence albumin quantification. METHODS: Albumin levels are determined in clinical laboratories mainly by the bromocresol green (BCG) spectrophotometric assay. The detection of serum albumin was investigated in HD patients and in healthy controls using an "albumin-detection index", defined as the ratio between BCG read-out (albumin-specific) to total albumin. The detection efficacy of albumin was also investigated in vitro, after glycoxidation, HOCl-mediated-oxidation, and metal-catalyzed-oxidation. Oncotic pressure was measured to assess albumin function. RESULTS: The albumin-detection index of patients was significantly lower compared with controls, correlating negatively with oxidative stress markers (serum advanced oxidation protein products-AOPP and glycoxidized serum albumin) and positively with serum albumin levels. The albumin-detection index was also decreased after in vitro oxidation. CONCLUSIONS: The study shows, both in vivo and in vitro, decreased detection of oxidized albumin by a commonly-used clinical assay, thus providing the molecular link between oxidative stress and hypoalbuminemia. Oxidative stress as reflected by hypoalbuminemia, rather than actual albumin levels, may be related to cardiovascular morbidity outcomes in HD patient.

Epoetin-alpha: preserving kidney function via attenuation of polymorphonuclear leukocyte priming.

BACKGROUND: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs. OBJECTIVESxi: To evaluate the effect of 20 weeks of epoetin-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease. METHODS: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate. esults: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC and PMNL counts and ALP activity following treatment. EPO retarded the deterioration in GFR. The percent of PMNLs expressing EPO-R was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated. CONCLUSIONS: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Cord blood lipids concentrations and their relation to body size at birth: possible link between intrauterine life and adult diseases.

Umbilical plasma levels of lipoproteins-cholesterol were measured in 480 normal newborns delivered by spontaneous vaginal delivery at 39 to 40 weeks of gestation. Plasma concentrations of lipids were related to fetal weight, abdominal and head circumference, and ponderal index at birth. Plasma concentration of low-density lipoprotein cholesterol (LDL-C) correlated negatively with abdominal circumference (AC), birth weight, and head circumference of newborns (p < 0.021, p < 0.023, p < 0.044, respectively). The baby with the smallest AC had the highest plasma concentration of LDL-C (p < 0.015). In the 165 neonates with ponderal index < 10th percentile, LDL-C was substantially elevated (p < 0.018). These findings suggest that disproportionate size at birth is associated with altered lipid metabolism. These abnormalities, if they persist, might lead to metabolic diseases in adulthood.