Serum Oxidized Albumin and Cardiovascular Mortality in Normoalbuminemic Hemodialysis Patients: A Cohort Study

Abstract

BackgroundSubstantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients.MethodsWe conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients’ survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA.ResultsAfter adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD.ConclusionsSerum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.

Predilution On-Line Hemodiafiltration Improves Albumin Redox in Maintenance Hemodialysis Patients

“…Furthermore, a previous study reported that higher serum levels of β2-MG (≥32.2 mg/L) were significant predictors of mortality in MHD patients, independent of HD duration, diabetes, malnutrition, or inflammation [18]. Moreover, an observational study performed in 249 MHD patients for 6.5 years revealed that higher levels of HNA were also significant predictors of mortality in normoalbuminemic MHD patients [19]. From these reports and from the result of our study, we conclude that pre-OL-HDF might attenuate the risk of cardiovascular disease and premature death in MHD patients via the effective removal of medium molecular uremic substances and Alb redox improvements, more so than those achievable by CHD using super-flux dialyzers.…”

Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study

“…[25][26][27] In addition, Lim et al found that the redox state of HSA is a positive predictor of mortality in normoalbuminemic HD patients. 28) Similarly, Jalan et al found that the 1-year survival rate for liver cirrhosis patients could be predicted by the concentration of reduced HSA in their plasma. 29) Taking into consideration the fact that modified albumin molecules lack multiple functions, Domenicali et al proposed that the concentration of reduced HSA should be measured to indicate the "effective albumin concentration" as a new indicator in lieu of the conventional parameter total albumin concentration.…”

Wishful Thinking: The Surprisingly Sparse Evidence for a Relationship between Oxidative Stress and Cardiovascular Disease in Hemodialysis Patients

“…Nine clinical studies have assessed the relationship between biomarkers of oxidative stress and CVD events, CVD-related mortality, and all-cause mortality in chronic hemodialysis patients (46,(52)(53)(54)(55)(56)(57)(58)(59). Four studies have assessed and demonstrated an association between biomarkers of oxidative stress and the development of new CDV events (51,57,58).…”

“…The association between oxidative stress and CVD-related mortality has been assessed in five studies, and an association was found in three studies (52,54,57) and absent in two (46,51). Interestingly, in the study by Grahl et al, CVD-related mortality was associated with the CYBA 242C/T polymorphism but not with the NADPH/myeloperoxidase polymorphism (46).…”