Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease

Abstract

Background Oxidative stress is enhanced in advanced chronic kidney disease (CKD) patients and recognized as a main contributor to cardiovascular disease. Carbonyl stress is also known to be enhanced in advanced CKD; however the precise relationship between oxidative stress and carbonyl stress is not clear. The aim of this study was to investigate potential relationships between oxidative stress, carbonyl stress, and renal function among predialysis patients with CKD. Methods A total of 32 predialysis CKD patients (22 male, 10 female) were divided into four groups according to their values for creatinine clearance (Ccr) (group A, C60 ml/min; group B, 45-59 ml/min; group C, 30-44 ml/min; group D, B29 ml/min). As main markers of oxidative and carbonyl stresses, the redox state of Cys-34 (free thiol group) of human serum albumin [HSA(Cys-34)-redox] and the carbonyl content of serum proteins were employed, respectively.Results The values for the fraction of both reversibly oxidized HSA [f(HNA-1)] and irreversibly oxidized HSA [f(HNA-2)] significantly increased with a decrease in renal function (group A, 21.0 ± 3.4 and 1.8 ± 0.3%; group D, 31.1 ± 4.1 and 2.7 ± 0.9%, respectively). The value for carbonyl content also significantly increased with a decrease in renal function (group A, 0.7 ± 0.1 nmol/mg protein; group D, 1.1 ± 0.2 nmol/mg protein). There was a significant positive correlation between carbonyl content and the f(HNA-2) value, while such a correlation was not observed between carbonyl content and the f(HNA-1) value, suggesting that there is a close relationship between serum protein carbonylation and irreversible albumin thiol oxidation. Conclusions There is a close relationship between oxidative stress and carbonyl stress and these are enhanced in correlation with the level of renal dysfunction among predialysis CKD patients.

Increased Low-Density Lipoprotein S-Homocysteinylation in Chronic Kidney Disease

“…Therefore, the increase in renal damage induces a rise in oxidative stress, thus increasing the quantity of these proatherogenic thiols linked to LDL. This is consistent with recent findings which have described that the plasma levels of the reduced form of albumin (albumin-Cys 34 -SH) decreased progressively with a decrease in renal function of CKD patients, leading to an increase of the oxidized form of protein (albumin-Cys 34 -S-S-X) [35]. …”

Serum Thiol/Disulfide Homeostasis in Hemodialysis, Peritoneal Dialysis, and Renal Transplantation Patients

“…Previous studies have supported our finding indicating that the uremic state is associated with low concentrations of glutathione and reduced thiols (SH), which continue to decrease with the progression of kidney failure in dialysis patients (16). In addition, Matsuyama et al showed that the redox state of Cys-34 (free thiol group) of human serum albumin correlated with the level of renal dysfunction in predialysis chronic kidney disease patients (17).…”

The redox state of recombinant human serum albumin and its optimal concentration for mouse embryo culture

“…HPLC system for measuring the albumin redox state Measurement of the albumin redox state was performed by a previously-reported HPLC method [Matsuyama et al 2009a;Matsuyama 2009b]. Briefly, the HPLC system consisted of an AS-8010 auto-sampler (using an injection volume of 2 µL of sample) and a CCPM double-plunger pump in conjunction with an SC-8020 system controller (all from Tosoh, Tokyo, Japan).…”