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

Abstract

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. 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, > or =60 ml/min; group B, 45-59 ml/min; group C, 30-44 ml/min; group D, < or =29 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. 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. 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.