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.

Figure 1

Correlations between serum fraction of human non-mercaptalbumin [f(HNA)] and clinical parameters in CKD patients. Age (A), blood urea nitrogen (C), ferritin (E), phosphate (G), intact-PTH (H) and FGF-23 (I) were significantly and positively correlated with f(HNA). Estimated glomerular filtration rate (eGFR) (B), hemoglobin (D), and sodium-chloride (F) were significantly and negatively correlated with f(HNA).