BACKGROUND: Oxidative stress and inflammation are common features and the main mediators of progression of chronic kidney disease (CKD) and its cardiovascular complications. Under normal conditions, oxidative stress activates the transcription factor, nuclear factor E2-related factor 2 (Nrf2), which is the master regulator of genes encoding antioxidant and detoxifying enzymes and related proteins. The available data on expression of Nrf2 and its key target gene products in CKD patients is limited. We therefore investigated this topic in a group of CKD patients on hemodialysis. METHODS: Twenty adult hemodialysis (HD) patients (aged 54.9 ± 15.2 years) and 11 healthy individuals (aged 50.9 ± 8.0 years) were enrolled. Peripheral blood mononuclear cells (PBMC) were isolated and processed for expression of nuclear factor-κB (NF-κB), Nrf2, heme oxygenase-1 and NADPH: quinoneoxidoreductase 1 (NQO1) by quantitative real-time polymerase chain reaction and western blot analysis. Plasma malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels were measured. RESULTS: Peripheral blood mononuclear cells from HD patients had significantly lower NQO1 and Nrf2 mRNA expressions (0.58 ± 0.35 vs. 1.13 ± 0.64, p = 0.005), and significantly higher NF-κB expression (2.18 ± 0.8 vs. 1.04 ± 0.22, p = 0.0001) compared to the healthy individuals. The NF-κB expression was inversely correlated with Nrf2 levels (r = -0.54, p < 0.01) in CKD patients. Plasma MDA and TNF-α levels were significantly higher in CKD patients than in the healthy individuals. CONCLUSIONS: Up-regulation of NFκB in the CKD patients' PBMC is coupled to down-regulation of Nrf2 and NQO1 expression. These observations are consistent with recent findings in CKD animals and point to the contribution of the impaired Nrf2 system in the pathogenesis of oxidative stress and inflammation in hemodialysis patients.
BACKGROUND: Oxidative stress and inflammation are common features and the main mediators of progression of chronic kidney disease (CKD) and its cardiovascular complications. Under normal conditions, oxidative stress activates the transcription factor, nuclear factor E2-related factor 2 (Nrf2), which is the master regulator of genes encoding antioxidant and detoxifying enzymes and related proteins. The available data on expression of Nrf2 and its key target gene products in CKDpatients is limited. We therefore investigated this topic in a group of CKDpatients on hemodialysis. METHODS: Twenty adult hemodialysis (HD) patients (aged 54.9 ± 15.2 years) and 11 healthy individuals (aged 50.9 ± 8.0 years) were enrolled. Peripheral blood mononuclear cells (PBMC) were isolated and processed for expression of nuclear factor-κB (NF-κB), Nrf2, heme oxygenase-1 and NADPH: quinoneoxidoreductase 1 (NQO1) by quantitative real-time polymerase chain reaction and western blot analysis. Plasma malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels were measured. RESULTS: Peripheral blood mononuclear cells from HDpatients had significantly lower NQO1 and Nrf2 mRNA expressions (0.58 ± 0.35 vs. 1.13 ± 0.64, p = 0.005), and significantly higher NF-κB expression (2.18 ± 0.8 vs. 1.04 ± 0.22, p = 0.0001) compared to the healthy individuals. The NF-κB expression was inversely correlated with Nrf2 levels (r = -0.54, p < 0.01) in CKDpatients. Plasma MDA and TNF-α levels were significantly higher in CKDpatients than in the healthy individuals. CONCLUSIONS: Up-regulation of NFκB in the CKDpatients' PBMC is coupled to down-regulation of Nrf2 and NQO1 expression. These observations are consistent with recent findings in CKD animals and point to the contribution of the impaired Nrf2 system in the pathogenesis of oxidative stress and inflammation in hemodialysis patients.
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