Hemodialysis Induces p66shc Gene Expression in Nondiabetic Humans: Correlations with Oxidative Stress and Systemic Inflammation

Objective Oxidative stress and inflammation characterize hemodialysis (HD) and are associated with malnutrition, cardiovascular disease, and poor clinical outcome. p66 shc stimulates oxidative stress and atherogenesis. The objective of the present study was to assess p66 shc expression levels in HD and their associations with inflammatory and oxidative stress markers. Design p66 shc messenger ribonucleic acid (mRNA) was compared with systemic oxidative stress and inflammation markers in control subjects and patients on HD before and after a single HD session in a cross-sectional analysis. Setting Outpatient hemodialysis unit. Patients The study included stable HD patients (n = 21, men/women: 18/3) who were on HD 3 times per week for a minimum of 8 weeks; age-matched control subjects (n = 22, men/women:17/5). Main Outcome Measure mRNA levels of p66 shc , tumor necrosis factor α (TNF-α), and pentraxin 3 (PTX3), p66 shc protein levels in white blood cells, lipid peroxidation (in the form of plasma thiobarbituric acid-reactive substance [TBARS]) and serum C-reactive protein. Results In patients on dialysis, of the p66 shc , TNF-α, and PTX3 mRNAs, p66 shc protein levels were higher ( P P shc mRNA directly correlated with TBARS ( r = 0.69, P = .0005) and with TNF-α mRNA ( r = 0.63, P = .003). These associations were confirmed in the whole study population (TBARS: r = 0.541, P = .0003; TNF-α: r = 0.581, P shc and TNF-α was detected. TNF-α was directly correlated with PTX3 both in HD patients ( r = 0.72, P = .0005) and in the whole study group ( r = 0.678, P shc and TNF-α mRNA nor p66 shc protein expression, whereas it further increased ( P = .002) PTX3 mRNA. As compared with predialysis levels, TBARS were reduced ( P shc remained directly correlated with TNF-α ( r = 0.901, P Conclusions Increased p66 shc gene expression correlates with TNF-α mRNA and with levels of markers of oxidative stress in HD. We suggest a novel link between HD-associated inflammation and p66 shc gene expression contributing to systemic oxidative stress.