| Section one:Plasma pentraxin3 in maintenance hemodialysis patients is associated with malnutrition and cardiovascular diseaseObjective:To investigate the relationship between plasma pentraxin3 (PTX3), malnutrition and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:Plasma was obtained from 98 MHD patients before and after undergoing hemodialysis and 50 age-matched healthy subjects. In a cross-sectional study, plasma PTX3 level was measured by enzyme-linked immunosorbant assay (ELISA). Spearman correlation, linear regression and binary logistic regression were used to assess the relationship between plasma PTX3 level and other laboratory parameters and CVD in MHD patients. Receiver operating characteristic (ROC) curves were used to assess the correlation with PTX3, hsCRP and CVD in MHD patients.Results:Plasma PTX3 level was significantly higher in HD patients compared with controls(1.87[1.34-2.50]ng/ml vs 1.11[0.86-1.51]ng/ml, P<0.001), and increased acutely after a single HD session (post-HD 2.18[1.80-3.14]ng/ml vs pre-HD 1.87[1.34-2.50]ng/ml, P<0.001). Patients with CVD had higher concentrations of PTX3 than their counterparts (2.20 [1.48-2.74]ng/ml vs 1.76 [1.25-2.26]ng/ml, P=0.029). In all MHD patients plasma PTX3 levels correlated negatively with body mass index(p=-0.248, P=0.014), pre-albumin(p=-0.218, P=0.031), total cholesterol (p=-0.265, P=0.008), triglyceride(p=-0.246, P=0.014), LDL-cholesterol(p=-0.254, P=0.012) and hemoglobin (p=-0.212, P=0.034); and positively with erythropoietin dose per week (p=0.184, P=0.007), cardiac troponin T (p=0.287, P=0.007) and carotid artery intima-media thickness (p=0.294, P=0.043). Linear regression analysis showed cardiac troponin T(β=0.334, P<0.001)and hemoglobin(β=-0.240, P=0.018) are independently associated with plasma PTX3 levels.High plasma PTX3 (>1.87ng/ml) level was positively and independently associated with CVD (OR=3.15,95%CI [1.17-8.50], P=0.024). ROC curves analysis showed the correlation between PTX3 and CVD more closely than hsCRP in patients whose hsCRP levels were higher than 3mg/L.The area under the curve for PTX3 and CRP was 0.665 (95%CI 0.502-0.827, P=0.047) and 0.562 (95%CI 0.399-0.724, P=0.458) respectively.Conclusion:PTX3 levels are markedly elevated in HD patients. HD procedure per se induces PTX3 elevation. Plasma PTX3 is associated with malnutrition and CVD in MHD patients.Plasma PTX3 could be a useful marker of inflammation and CVD risk factors in MHD patients. Section two:Hemodialysis induces peripheral blood mononuclear cell nuclear factor kappa B activationObjective:The aim of the study was to measuring nuclear factor kappa B (NF-κB) activity of peripheral blood mononuclear cell (PBMC) and oxidative stress in maintenance hemodialysis (MHD) patients and evaluating the correlation of NF-κB activity and cardiovascular disease (CVD) in these patients.Methods:Blood was obtained from 32 MHD patients before and after undergoing hemodialysis and 12 age-matched healthy subjects. In a cross-sectional study, nuclear extracts NF-κB activity of PBMC and plasma pentraxin3(PTX3) was measured by enzyme-linked immunosorbant assay (ELISA) and serum total antioxidant capacity (T-AOC) and malondialdehyde (MDA) was measured by colorimetry. High sensitive C-reactive protein (hsCRP) was determined by routine procedures at the department of clinical chemistry. Pearson correlation and linear regression were used to assess the relationship between NF-κB activity and other laboratory parameters. Binary logistic regression was used to assess the correlation of NF-κB activity and CVD in MHD patients. Receiver operating characteristic (ROC) curves were used to assess the correlation with NF-κB activity, PTX3, hsCRP and CVD in MHD patients.Results:NF-κB activity of PBMC(1142.4±413.0ng/mg nuclear extracts vs 208.3±39.5ng/mg nuclear extracts, P<0.001) and plasma PTX3(2.28[2.01-2.97] ng/ml vs 1.42[0.90-1.97]ng/ml, P<0.001) was significantly higher in MHD patients compared with controls, and increased acutely after a single HD session (NF-κB activity of post-HD 2076.5±690.1ng/mg nuclear extracts vs pre-HD 1142.4±413.0 ng/mg nuclear extracts, P<O.001; and PTX3 of post-HD 2.85[2.54-3.78] ng/ml vs pre-HD 2.28[2.01-2.97]ng/ml, P<0.001). Serum hsCRP (3.2[1.1-8.9]mg/L vs 0.5[0.3-1.0]mg/L, P<0.001),T-AOC (21.9±6.6U/ml vs 15.7±2.3U/ml, P<0.001) and MDA (6.80±0.86nmol/ml vs 3.89±0.51nmol/ml, P<0.001) in MHD patients was also significantly higher compared with controls. Serum T-AOC decreased significantly after a single HD session (13.6±5.0U/ml vs 21.9±6.6U/ml, P<0.001). Patients with CVD had higher NF-κB activity than their counterparts (1308.8±413.0ng/mg nuclear extracts vs 899.1±277.2ng/mg nuclear extracts, P=0.004). In all MHD patients NF-κB activity correlated positivelyly with white blood cell count(r=0.454, P=0.009), hsCRP (r=0.590, P<0.001), PTX3 (r=0.68O, P<0.001), cardiac troponin T (r=0.409, P=0.020), MDA (r=0.390, P=0.027) and carotid artery intima-media thickness (r=0.541, P=0.011). Linear regression analysis showed white blood cell count (β=0.338, P=0.028), hsCRP (β=0.440, P=0.005), PTX3(β=0.487, P=0.004), MDA(β=0.319, P=0.029) and carotid artery intima-media thickness ((3=0.453, P=0.032) are independently associated with NF-κB activity. High NF-κB activity(> 1170.0 ng/mg nuclear extracts) was positively and independently associated with CVD (OR=8.47,95%CI [1.69-87.41], P=0.022). ROC curves analysis showed the correlation between NF-κB activity and CVD more closely than PTX3 and hsCRP. The area under the curve for NF-κB activity, PTX3 and hsCRP was 0.791 (95%CI 0.633-0.950, P=0.006),0.785 (95%CI 0.628-0.943, P=0.007) and 0.711(95%CI 0.514-0.907, P=0.046) respectively.Conclusions:NF-κB activity of PBMC are markedly elevated in MHD patients. HD procedure per se induces NF-κB activation. NF-κB activity is associated with oxidative stress and CVD in MHD patients. NF-κB activity of PBMC could be a useful marker of inflammation and risk factors of CVD in MHD patients. Section three:Serum hepcidin in maintenance hemodialysis patients is associated with iron status and microinflammationObjective:To investigate the relationship between serum hepcidin, iron status and microinflammation in maintenance hemodialysis (MHD) patients.Methods:Serum was obtained from 48 MHD patients before and after undergoing hemodialysis and 20 age-matched healthy subjects. In a cross-sectional study, serum hepcidin and IL-6 level was measured by enzyme-linked immunosorbant assay (ELISA). Spearman correlation and linear regression were used to assess the relationship between serum hepcidin level and other laboratory parameters in MHD patients.Results:Serum hepcidin (225.6[146.4-455.9]ng/ml vs 90.4[54.5-171.5]ng/ml, P<0.05), IL-6 (48 [35.0-97.2]pg/ml vs 43.9 [26.5-51.6]pg/ml, P<0.05) and hsCRP (3.6[1.4-7.8]mg/L vs 0.9[0.5-1.5]mg/L, P<0.05) level was significantly higher in MHD patients compared with controls. In all MHD patients serum hepcidin levels correlated positively with ferritin(p=0.892, P<O.001), transferrin saturation (p=0.289, P=0.049) and IL-6 (p=0.439, P=0.002); and negatively with unsaturated iron-binding capacity (p=-0.570, P<0.001), total iron-binding capacity (p=-0.552, P<0.001) and transferrin (p=-0.532, P<0.001). Linear regression analysis showed ferritin (β=0.736, P<0.001) and total iron-binding capacity(P=-0.204, P=0.034) are independently associated with serum hepcidin levels.Conclusion:Serum hepcidin levels are markedly elevated in MHD patients. Serum hepcidin levels are associated with iron status and microinflammation in MHD patients.The new ELISA method for measurement of serum hepcidin was available for clinical practice.Serum hepcidin, hsCRP and markers of iron metabolism together are indicators of iron administration, and may play an important role in treating anemia in MHD patients.
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