Non-mercaptalbumin, Oxidized Form of Serum Albumin, Significantly Associated with Renal Function and Anemia in Chronic Kidney Disease Patients

Abstract

Oxidative stress plays a major role in development of cardiovascular disease in patients with chronic kidney disease (CKD). Human mercaptalbumin (HMA), a reduced form of serum albumin, and non-mercaptalbumin (HNA), an oxidized form of serum albumin, are known as indicators for evaluating oxidative stress in systemic circulation, including end-stage renal disease cases. We investigated factors associated with fraction of HNA [f(HNA)] in 112 pre-dialysis CKD patients (63.6 ± 14.0 years old; 59 males, 53 females) using a newly established anion-exchange column packed with hydrophilic polyvinyl alcohol gel as well as high performance liquid chromatography. Mean f(HNA) in our CKD patients was 30.0 ± 6.1%, higher than that previously reported for healthy subjects. In multiple regression analysis, age (β = 0.200, p = 0.014), eGFR (β = −0.238, p = 0.009), hemoglobin (β = −0.346, p < 0.001), and ferritin (β = 0.200, p = 0.019) were significantly and independently associated with f(HNA) (R2 = 0.356, p < 0.001). In addition, factors related to CKD-mineral and bone disorder (CKD-MBD), including intact-PTH (β = 0.218, p = 0.049) and 1,25-dihydroxyvitamin D (1,25(OH)2D) (β = −0.178, p = 0.040), were significantly and independently associated with serum f(HNA) (R2 = 0.339, p < 0.001), whereas fibroblast growth factor-23 was not. These findings indicate the importance of management of hemoglobin and ferritin levels, as well as appropriate control of CKD-MBD factors for a better redox state of serum albumin in CKD patients.

A rapid method for measuring serum oxidized albumin in a rat model of proteinuria and hypertension

“…The results from our study showed that the percentage of oxidized albumin was significantly higher in the disease model than in the control group and that this change was reversed by the anti-oxidant drug Tempol. These results were consistent with human renal function data 7,29 . To further confirm our results, we have compared serum oxidized albumin with urinary 8-isoprostane levels, which is a commonly used marker to indicate the oxidative stress.…”

Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease

“…An exception is a study by Nakatani et al, in which the concentration of PTH correlated with the concentration of the oxidized form of albumin in which the thiol group Cys-34 formed a disulfide bond. However, no similar correlation was found for FGF-23 concentration [226].…”

Serum Albumin Redox States: More Than Oxidative Stress Biomarker

“…Increases in HNA levels have been reported in these patients [11,15,19,32,42]. Most of these studies attended to the sum of oxidized ALB isoforms (i.e., HNA-1 + HNA-2), as determined by HPLC or colorimetric methods [15,19,32,[65][66][67][68][69][70][71]. Still, some studies employed LC-MS/MS and indicated that an increase in cysteinylated ALB level was prominent in CKD patients [11,42].…”

“…Still, some studies employed LC-MS/MS and indicated that an increase in cysteinylated ALB level was prominent in CKD patients [11,42]. The oxidized ALB levels paralleled the loss of renal function [32,[67][68][69][70], and "oxidative" uremic toxin has been considered responsible for the ALB oxidation [34,72]. Hemodialysis treatment reversed the serum ALB redox state to a more reduced state [42,65]; reducing agents in dialysis membranes might be involved in the reversal, remaining an open question.…”