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.
Highlights
human non-mercaptalbumin (HNA) and Human mercaptalbumin (HMA) have been shown to be good indicators for evaluating oxidative stress in systemic circulation of various types of patients, including those with chronic liver failure[7,8] and ESRD9,10
We investigated factors associated with serum levels of HNA and HMA in pre-dialysis chronic kidney disease (CKD) patients using a newly established, highly sensitive assay based on an anion-exchange column packed with a hydrophilic polyvinyl alcohol gel, along with high performance liquid chromatography (HPLC)
Our findings clearly demonstrated that decreased renal function, represented by lower Estimated glomerular filtration rate (eGFR), was strongly associated with f(HNA) in pre-dialysis CKD patients
Summary
HNA and HMA have been shown to be good indicators for evaluating oxidative stress in systemic circulation of various types of patients, including those with chronic liver failure[7,8] and ESRD9,10. A higher HNA level has been reported to be a considerable risk factor for CVD in patients undergoing hemodialysis and peritoneal dialysis[10,11]. It is clinically important to measure HNA and HMA in patients with an elevated risk of CVD, i.e., those with CKD and ESRD. Few investigations have examined the relationship between serum fraction of HNA [f(HNA)], a serum marker of oxidative stress determined using the formula HNA/(HNA + HMA)*1009,12, and clinical parameters in pre-dialysis CKD patients[13]
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