ABSTRACT
Dialysis is associated with an increased generation of oxidants, which play an important part in the development of endothelial dysfunction and atherogenesis. Markers of oxidative stress include F2-isoprostanes and ethane. Measurements in dialysis patients before dialysis showed higher levels of esterified plasma F2-isoprostanes (1.62 +/- 0.73 ng/mL) than in control subjects (0.27 +/- 0.10 ng/mL) (P < 0.001). Furthermore, levels also correlated with high plasma C-reactive protein (CRP) levels (r =.48, P = 0.015). Breath ethane levels for dialysis patients (N = 19) were 6.32 +/- 3.16 pmol/kg-min, in contrast to 3.08 +/- 1.50 pmol/kg-min in control subjects (N = 11, P < 0.005). Analysis to investigate the relationship between CRP levels and outcome indicated that there was a significant difference in mortality rate over a 3-year period between patients with low and high CRP values (P < 0.001). Patients with high CRP (> 16.8 mg/L) levels were more than twice as likely to die as patients with low CRP levels (relative risk [RR] = 2.16; 95% confidence interval [CI], 1.50-3.09). CRP values were a significant predictor of mortality even after controlling for diabetes, albumin, ferritin, and age at commencement of dialysis. The RR for CRP after adjustment was 1.58 (95% CI, 1.06-2.34, P = 0.024). There were no significant interactions between CRP and other predictors of mortality, indicating that high CRP levels have an additive effect on the mortality risk. These findings show that hemodialysis patients are exposed to both oxidative stress and inflammation.
Subject(s)
Acute-Phase Reaction/etiology , F2-Isoprostanes/metabolism , Oxidative Stress , Renal Dialysis/adverse effects , Acute-Phase Reaction/metabolism , C-Reactive Protein/metabolism , Diabetes Complications , Diabetes Mellitus/metabolism , Follow-Up Studies , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Lipid Peroxidation , Longitudinal Studies , ROC Curve , Reactive Oxygen Species/metabolism , Risk Assessment , Serum Amyloid A Protein/metabolism , Survival AnalysisABSTRACT
Chronic inflammation, the associated cardiovascular disease, and attendant high mortality remain huge problems in the HD population. Determining the predominant causal factors in the triggering and maintenance of this inflammatory state is of paramount importance in formulating treatment strategies for individuals and for centers. In most cases, causation is multifactorial and several different areas of the HD process need to be considered. In this respect, the water system in HD centers is certainly one parameter that demands careful design, rigorous monitoring and strict adherence to effective disinfection protocols. In this way it may be possible not only to reduce levels of inflammatory markers, but to improve performance in other clinical areas, such as EPO therapy, and perhaps outcomes in the HD population.
