Oxidative status and prevalent cardiovascular disease in patients with chronic renal failure treated by hemodialysis

BACKGROUND: Hemodialysis (HD) patients are exposed to oxidative stress which contributes to cardiovascular disease (CVD). The purpose of this study was to investigate the oxidative and antioxidative status in HD patients with (CVD+, n = 38) and without (CVD-, n = 67) prevalent CVD. PATIENTS AND METHODS: A total of 105 HD patients and 21 healthy controls were assessed for lipid peroxidation indices (plasma malondialdehyde (MDA)), oxidizability of apolipoprotein B-containing lipoproteins (apo B-deltaMDA) and red blood cells (RBC-MDA) together with various components of the antioxidant system in plasma (paraoxonase/arylesterase activities, total carotenoids, vitamins C and E) and RBC (superoxide dismutase and glutathione peroxidase activities). RESULTS: Plasma MDA and RBC-MDA were significantly higher, vitamin C and total carotenoid levels were significantly lower in both CVD+ and CVD- HD groups than in the control group. Plasma MDA levels were significantly higher and serum paraoxonase activity, uric acid and albumin levels were significantly lower in patients with CVD+ HD patients compared to those of the CVD- patients. CONCLUSION: This study suggests that the elevated level of plasma MDA and the lower activity of paraoxonase could contribute to the increased incidence of cardiovascular disease in hemodialysis patients.     

Oxidative stress in renal anemia of hemodialysis patients is mitigated by epoetin treatment

BACKGROUND/AIMS: Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia. METHODS: In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed. RESULTS: In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced. CONCLUSION: Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.     

Serum hepatocyte growth factor is associated with viral hepatitis, cardiovascular disease, erythropoietin treatment, and type of heparin in haemodialysis patients.

BACKGROUND: Increased serum hepatocyte growth factor (HGF) level is a part of the counter-system against tissue damage and predicts mortality in maintenance haemodialysis (HD) patients. We studied which of the common co-morbid and clinical conditions, and surrogates of metabolic disorders or specific organ damage determine HGF levels in these subjects. METHODS: In 86 patients, pre-dialysis serum HGF, soluble endothelial markers--such as thrombomodulin (TM), von Willebrand factor and plasminogen activator inhibitor-1--and hepatitis B and C markers were measured by ELISAs. Inflammatory reactants such as C-reactive protein (CRP), alpha(1)-antitrypsin, alpha(1) acid-glycoprotein, and immunoglobulin M and G were assayed by nephelometry, and lipoprotein(a) was determined by ELISA. Cardiovascular disease (CVD) was identified on a clinical basis. RESULTS: Serum HGF was directly associated with the presence of viral hepatitis, alanine aminotransferase and TM levels, time on HD, the presence of CVD, CRP and alpha(1)-antitrypsin levels, use of unfractionated heparin (UFH) (vs enoxaparin) during HD, dose of UFH, use of recombinant erythropoietin (rHuEpo) treatment, and Kt/V. In 36 patients not treated with rHuEpo, HGF directly correlated with haemoglobin, but not with endogenous Epo levels. There was no association between HGF and the other endothelial and inflammatory markers, gender, age, smoking, cause of renal failure, body mass index, normalized protein catabolic rate, dialysate buffers, dialysers, blood pressure, antihypertensive treatment, leukocyte and platelet counts, albumin, fibrinogen, lipoprotein(a), markers of iron and calcium-phosphorus metabolism, or metabolic acidosis. Positive viral hepatitis markers, prevalent CVD and rHuEpo treatment (in descending order of significance) were independent predictors of high HGF level. In another 20 HD patients, a 4-week course of rHuEpo treatment resulted in a significant 17% increase in circulating HGF levels. CONCLUSION: Serum HGF levels in HD patients are determined by inflammatory conditions such as viral hepatitis and CVD, increase in response to rHuEpo treatment, and may be influenced by type and dose of heparin used during HD procedures.     

Changes in the inflammatory and oxidative stress markers during a single hemodialysis session in patients with chronic kidney disease

Background: Cardiovascular disease (CVD) is a common cause of morbidity and mortality in end-stage renal disease (ESRD) patients on hemodialysis (HD) among whom it is 5–20 times higher than in the general population. Some of the nontraditional risk factors such as oxidative stress and inflammation are related to the progress of CVD in HD patients. Several, but not all studies, reported that inflammatory and oxidative stress markers are increased during a single session of HD, mimicking changes that occur during acute immune activation. This study was taken up to evaluate the changes in the inflammatory and oxidative stress markers during a single HD session in patients with chronic kidney disease.

Methods: Twenty-five ESRD patients on maintenance HD and 25 controls were included in the study. Blood samples were obtained from the patients before starting of hemodialysis (pre-HD) and after completion of hemodialysis (post-HD). The changes in serum Pentraxin-3, hs-CRP, malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP) levels were measured in pre- and post-HD ESRD patients and compared with healthy control group.

Results: This study found increased levels of Pentraxin-3, hs-CRP, MDA, and decreased level of FRAP in HD patients compared to controls.

Conclusions: Hemodialysis procedure contributes to inflammation and oxidative stress.     

Elevated serum concentration of cardiotoxic lipid peroxidation products in chronic renal failure in relation to severity of renal anemia

Patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) and 4-hydroxylnonenal (HNE) were found in plasma of uremic patients indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The catabolism and action of those products was already intensively studied. As highly reactive metabolites they are able to bind to proteins, nucleic acids, and other molecules. Doing so, they exert molecular signal effects in cells and are able to exacerbate tissue and organ damage, e.g. cardiotoxic effects. Since renal anemia was shown to promote oxidative stress as well, the aim of our investigation was to examine its role in HD patients. Therefore, two groups of HD patients were investigated (group I Hb < 10 g/dl, group II Hb > 10 g/dl) and serum concentrations of MDA, HNE, and of protein carbonyls, a marker for protein oxidation, were determined. All HD patients had significantly higher levels of the LPO products MDA and HNE compared with controls. However, group I patients showed higher MDA and HNE concentrations compared to group II patients. The same result could be seen for protein carbonyls. During HD concentration of both LPO products decreased. However, this was not the case for protein carbonyls. These results lead to the conclusion that optimized correction of the renal anemia may result in a significant reduction of oxidative stress and therefore in the reduction of organ tissue damage. In this way correction of renal anemia will reduce the cardiovascular risk and comorbidity of HD patients improving their prognosis.     

Oxidative stress and ferritin levels in haemodialysis patients.

BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin may have other effects in addition to its role in storing intracellular iron. This study was performed to determine any relationships between markers of OS, nutrition and inflammation in HD patients with normal and high ferritin levels. METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin therapy and 22 healthy controls. HD patients were divided into two groups: 17 with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP), anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI, paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid, apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein B MDA, and lymphocyte levels in the HD patients with normal and high ferritin levels were similar. The OS markers of HD patients did not differ, whether or not they received intravenous iron supplementation or had transferrin saturations < 50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which results in the reduction of total anti-oxidant capacity and also have an increased inflammation status. We could not find a relationship between ferritin level and OS markers in HD patients receiving erythropoietin.     

Endothelial dysfunction marker von Willebrand factor antigen in haemodialysis patients: associations with pre-dialysis blood pressure and the acute phase response.

BACKGROUND: Increased plasma soluble von Willebrand factor antigen (vWF : Ag) level, a marker of vascular endothelial cell dysfunction, is a strong predictor of atherosclerotic cardiovascular disease (CVD) in the general population. We studied cross-sectional associations between vWF : Ag level, prevalence of CVD, and related factors including pre-dialysis arterial blood pressure (BP) and some markers of inflammation in maintenance haemodialysis (HD) patients. Methods and results. Plasma vWF : Ag level measured by an enzyme-linked immunosorbent assay (ELISA) was higher in 110 HD patients than in 20 controls. On bivariate regression analysis, vWF : Ag level was directly associated with the presence of CVD, age, fibrinogen and the use of enoxaparin (vs unfractionated heparin) during HD procedures, and inversely with albumin and pre-dialysis BP. The patients with prevalent CVD were older, had higher vWF : Ag, white blood cell and platelet counts, fibrinogen and triglycerides, lower albumin levels, and were less frequently on combination antihypertensive therapy. Multivariable analyses identified low pre-dialysis BP, hypoalbuminaemia and hyperfibrinogenaemia (in descending order of significance) as independent predictors of high vWF : Ag level. There were no associations between vWF : Ag levels and gender, ABO blood type, smoking, body mass index, renal failure cause, duration of HD therapy, K(t)/V, normalized protein catabolic rate, dialysate buffers, dialysers, viral hepatitis, erythropoietin treatment, specific antihypertensive drugs, haemoglobin, white blood cell and platelet counts, liver enzymes, phosphorous, total cholesterol, and triglycerides. CONCLUSION: Elevated plasma levels of endothelial dysfunction marker vWF : Ag in maintenance HD patients are associated with established cardiovascular mortality risk factors such as low pre-dialysis blood pressure and the activated acute phase response.     

Oxidative stress and cardiovascular disease in dialyzed patients

Background/Aim: Oxidative damage has been suggested to play a key role in accelerated atherosclerosis and to be involved in cardiovascular disease (CVD) of dialyzed patients who are at risk of increased oxidative stress. The purpose of the present study was to examine the relationship between the severity of CVD and some markers of oxidative stress and antioxidant activity in our hemodialyzed (HD) and peritoneal dialysis (PD) patients. Methods: Plasma reactive oxygen metabolites, malondialdehyde and 4-hydroxynonenal (MDA-4HNE), thiols, alpha-tocopherol, and total antioxidant status (TAS) were measured in 55 HD and in 16 PD patients. CVD was considered as the result of variably combined cardiac, cerebral, and vascular pathologies which were scored and grouped in a single CVD index and analyzed with respect to the markers of the oxidative status. 16 normal subjects served as controls. Results: All patients showed evidence of increased oxidative stress which was more severe in HD than in PD patients and which was exacerbated by HD. When cardiac, cerebral, and vascular diseases were analyzed separately, plasma MDA-4HNE and TAS were significantly higher in more severely affected HD patients, but not in PD patients. In HD patients the CVD index was directly correlated with both MDA-4HNE and TAS (r = 0.42, p < 0.01; r = 0.39, p < 0.01) and inversely correlated with alpha-tocopherol (r = -0.32, p < 0.05). MDA-4HNE and TAS were directly correlated in HD patients and inversely correlated in control subjects. Conclusions: Our data show that, in spite of increased antioxidant defense, there is a relationship between the degree of lipid peroxidation and the severity of CVD in HD patients. Moreover, these data underscore the utility of MDA-4HNE, alpha-tocopherol, and TAS in the evaluation of cardiovascular disease.     

Possible new role of monocyte chemoattractant protein-1 in hemodialysis patients with cardiovascular disease

AIMS: Reactive oxygen species have been implicated in increased vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) levels in vascular cells, which may promote atherosclerosis progression. METHODS: We studied the association between pre-dialysis plasma levels of VEGF and MCP-1 in 45 hemodialysis (HD) patients with and without cardiovascular disease (CVD) in conditions of increased oxidative stress (SOX). RESULTS: Compared to the controls, HD patients, especially those with CVD, showed a significant increase in plasma concentrations of Cu/Zn superoxide dismutase (Cu/Zn SOD), C-reactive protein (CRP), MCP-1 and VEGF. The levels of CRP, MCP-1 and VEGF were more increased in patients with CVD than in patients without CVD (all p < 0.01). VEGF strongly and positively correlated with MCP-1 only in HD patients with CVD. Additionally, both VEGF and MCP-1 were associated with Cu/Zn SOD in the whole HD group. CONCLUSION: For the first time our data indicate a correlation between VEGF and MCP-1 levels in HD patients with CVD in conditions of increased SOX. This interaction may reflect the new role of MCP-1 as an arteriogenic factor in HD patients with CVD.     

Evaluation of oxidative stress after repeated intravenous iron supplementation

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.     

Antioxidant therapy in hemodialysis patients: a systematic review

Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinical outcomes (3 studies). The majority were small trials using a nonrandomized open-label design with a single HD group (no HD controls). Alpha-tocopherol was the most investigated antioxidant, with 20/25 studies reporting that this vitamin decreased oxidative stress, and one clinical outcome trial in 196 patients finding that it protected against secondary CVD. Studies using vitamin C were more equivocal, with 4/11 showing decreased oxidative stress and one clinical outcome trial showing no effect on morbidity or mortality. N-acetylcysteine was the most efficacious agent, with 4/4 studies indicating a decrease in oxidative stress and one trial (n=134) showing reduced CVD events. Seven studies have used therapy containing a combination of antioxidants, with five of these reporting decreased oxidative stress. Most intervention studies in HD patients, such as statin therapy and increased dialysis dose, have failed to show improvement in CVD outcomes. Two intervention trials using different antioxidants have found CVD benefits, suggesting that this line of therapy is effective in this resistant population. These studies require validation in larger, adequately powered trials.     

The Relationship Between Leptin Level and Oxidative Status Parameters in Hemodialysis Patients

Both serum leptin level and oxidative stress are increased in hemodialysis (HD) patients. In the present study, we aimed to investigate whether there is association between oxidative status and leptin level in HD patients. Thirty-five HD patients and 25 healthy controls were enrolled in the present study. Serum leptin level, total peroxide (TP) level, total antioxidant capacity (TAC), and oxidative stress index (OSI) were determined. Serum leptin level, TP level, and OSI were significantly higher in HD patients than controls (all P  < 0.001) while TAC was lower ( P  < 0.001). In HD patients, serum leptin level was significantly correlated with TP level and OSI ( r  = 0.372, P  <  0.001 and r  = 0.409, P  < 0.001, respectively). The correlation of serum leptin level with TP level and OSI remained statistically significant after adjusting for age, gender, and body-fat percentage ( r  = 0.446, P  < 0.001 and r  = 0.463, P  < 0.001, respectively). Hyperleptinemia seems to be associated with increased oxidative stress in HD patients, and this association may provide better understanding about the disorders related to either elevated serum leptin levels and/or increased oxidative stress in HD patients.     

Carotid artery intima-media thickness correlates with oxidative stress in chronic haemodialysis patients with accelerated atherosclerosis.

BACKGROUND: Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). Increased oxidative stress might be the major factor leading to high cardiovascular mortality rate in HD patients. The aim of our study was to clarify effects of uraemia and dialysis on oxidative stress parameters and explore the relation between oxidative stress markers and carotid artery intima-media thickness (CIMT) as an indicator of atherosclerosis. METHODS: Twenty chronic HD patients, 20 predialytic uraemic patients and 20 healthy subjects were included in the study. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS: Both chronic HD and predialytic uraemic patients had enhanced oxidative stress indicated by higher levels of nitrite/nitrate, TBARS and PCO, and lower levels of P-SH, SOD, CAT and GPx compared to controls. HD patients had significantly higher CIMT and nitrite/nitrate while significantly lower P-SH,vitamin E, SOD, CAT and GPx compared to predialytic uraemic patients. There was a significant positive correlation between CIMT and TBARS (r = 0.38, P = 0.003) and nitrite/nitrate levels (r = 0.41, P = 0.001), while there was a significant negative correlation between CIMT and SOD (r = -0.35, P = 0.01), CAT (r = -0.65, P < 0.001) and P-SH levels (r = -0.50, P < 0.001). A linear regression analysis showed that TBARS were still significantly and positively correlated with CIMT (P = 0.001), while CAT and P-SH were significantly and negatively correlated with CIMT (P = 0.002 and P = 0.048, respectively). CONCLUSIONS: HD exacerbates oxidative stress and disturbances in antioxidant enzymes in uraemic patients. We propose that serum TBARS and nitrite/nitrate can be used as positive determinants, while erythrocyte SOD, CAT and P-SH may be used as negative determinants of atherosclerosis assessed by CIMT in uraemic and HD patients.     

Effects of vitamin supplementation on microcirculatory disturbance in hemodialysis patients without peripheral arterial disease

AIMS: Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury. PATIENTS AND METHODS: Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured. RESULTS: Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation. CONCLUSIONS: Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.     

Serum fetuin-A levels link inflammation and cardiovascular calcification in hemodialysis patients

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD). An elevated incidence of cardiovascular calcifications (CVC) is observed in HD. Fetuin-A is an important inhibitor of CVC. Reduced fetuin-A levels associate with inflammation and increased cardiovascular (CV) mortality in HD. In this study we investigated the association of fetuin-A levels and CVC. METHOD: We evaluated a cohort of 115 patients (67 males), aged 63 +/- 16 years with a HD vintage >or=9 months. Presence of CVC was assessed by ultrasound imaging of the abdominal aorta, common carotid arteries, bilateral ilio-femoral axis, aortic and mitral cardiac valves. The presence of CVC was analyzed as a CVC score (CVCS) (0-7) according to the number of CVC sites. Patients were arbitrary stratified in three groups: group I (CVCS = 0), group II (0 < CVCS < 6) and group III (CVCS >or= 6). Patients without CVC were younger, non-diabetic and with a negative history for CV events. RESULTS: Patients with evidence of CVC in more than 5 sites had lower serum fetuin-A levels (0.41 +/- 0.22 g/l) compared to patients with CVCS = 0 (0.51 +/- 0.17 g/l, p = 0.048). In addition a worse CVCS was associated with higher serum levels of C-reactive protein (p = 0.002) and fibrinogen (p < 0.001). Serum fetuin-A levels lower than 0.290 g/l were associated with higher risk of a worse CVCS, independently from traditional risk factors. CONCLUSION: Chronic inflammation in HD patients leads to lower serum fetuin-A levels. The present study confirms the independent and significant association between reduced serum fetuin-A levels and multi-site CVC in HD.     

Oxidative stress - a link between endothelial injury, coagulation activation, and atherosclerosis in haemodialysis patients

BACKGROUND/AIM: Recently emerging evidence suggests that oxidative stress (SOX) may participate in atherogenesis. The aim of the present study was to establish whether enhanced SOX, involving endothelial injury, activation of coagulation, and inflammatory reaction, could be implicated in atherosclerotic diseases in haemodialysis (HD) patients. METHODS: Markers of SOX, endothelial injury, coagulation, and cytokines, were measured in the plasma of HD patients with and without cardiovascular disease (CVD), and of healthy controls by ELISA methods. Remodeling of the carotid arteries was assessed by measuring the intima-media thickness (IMT) as a surrogate of atherosclerotic disease in all groups. RESULTS: Markers of SOX, endothelial injury, and extrinsic coagulation pathway activation and IMT values were significantly elevated in HD patients, especially in those with CVD when compared with the control group. The von Willebrand factor antigen (vWF:Ag) levels were more increased in the patients with CVD than in those without. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were significantly higher only in the HD group with CVD when compared with the controls. The IMT was strongly and directly correlated with Cu/Zn superoxide dismutase. Both IMT and Cu/Zn superoxide dismutase were positively correlated with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor, prothrombin fragment F1 + 2, monocte chemo-attractant protein 1, macrophage inflammatory protein 1 beta, and tumour necrosis factor alpha levels. Multivariate analysis identified vWF:Ag as the only independent variable significantly associated with an increased IMT. CONCLUSIONS: The present study suggests that enhanced SOX, involved pro-atherogenic cytokine and chemokines levels, endothelial injury, and coagulation activation may constitute a pathway for accelerated atherosclerosis in HD patients. The significant, independent association between IMT and vWF:Ag should be assessed in future studies to determine whether vWF:Ag elevation is causative or a by-product of the increased IMT.     

Comparison of novel risk factors for cardiovascular disease between hemodialysis patients with and without protein-energy wasting

Purpose

The present study was designed to compare novel risk factors for cardiovascular diseases (CVD) between hemodialysis (HD) patients with or without protein-energy wasting (PEW) for determining novel risk factors for CVD in HD patients with PEW.

Methods

In this cross-sectional study, 291 HD patients were randomly selected from among 2,302 adult HD patients in Tehran hemodialysis centers. The presence of PEW in HD patients was determined by subjective global assessment. In addition, 4 mL blood was obtained before dialysis and analyzed for serum concentrations of novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)].

Results

Serum CRP and sICAM-1 were significantly higher in HD patients with PEW as compared to those without PEW (P < 0.01), whereas there were no significant differences in serum sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a) between the two groups. Serum CRP and sICAM-1 were significantly higher in HD patients with PEW type IIa and IIb than in those with PEW type I (P < 0.01).

Conclusion

The present study indicates that serum CRP and sICAM-1, as two CVD risk factors, increase in HD patients with PEW as compared to those without PEW and these increases occur in HD patients with PEW type IIa and IIb who have inflammation.     

Relations between oxidative stress,hepatocyte growth factor,and liver disease in hemodialysis patients

BACKGROUND: Hepatocyte growth factor (HGF) and copper/zinc superoxide dismutase (Cu/Zn SOD) protect against tissue injury, including that due to oxidative stress (SOX). We studied whether they could be associated with each other, SOX markers, prevalence of viral hepatitis, and cardiovascular disease (CVD) and their laboratory surrogates in maintenance hemodialysis (HD) patients. METHODS: In 24 patients, pre-dialysis serum HGF, plasma Cu/Zn SOD, total lipid peroxides, and serum autoantibodies against oxidized LDL were measured by ELISAs. Viral hepatitis B and C markers were determined by third generation microparticle ELISAs, and CVD was identified on a clinical basis. Results: In HD patients, circulating HGF, Cu/Zn SOD, and the other SOX markers were higher than in healthy controls, and HGF directly correlated with Cu/Zn SOD levels (P = 0.0006). Both HGF (P = 0.021) and Cu/Zn SOD (P=0.017) were positively associated with prevalence of viral hepatitis and serum alanine aminotransferase activity (P = 0.021 and P=0.040, respectively). Presence of CVD directly correlated with HGF (P = 0.001) but not with Cu/Zn SOD levels (P = 0.087). Circulating HGF positively related to serum C-reactive protein (P = 0.043). In patients without viral hepatitis and CVD, both HGF and Cu/Zn SOD were lower than in those with, and higher than in healthy controls. CVD (P = 0.003) and viral hepatitis (P = 0.024) were independent predictors of increased HGF, while positive viral hepatitis marker predicted increased Cu/Zn SOD levels (P = 0.019) in HD patients. There were no associations between HGF and the SOX markers in controls. Conclusions: In maintenance HD patients, circulating Cu/Zn SOD and HGF levels are increased, likely as a part of the reparatory reaction against liver damage. Viral hepatitis status and liver function should be considered in further studies of Cu/Zn SOD in these subjects.     

Reduction of serum antioxidative capacity during hemodialysis

Background Hemodialysis (HD) is thought to exacerbate oxidative stress (OS). The purpose of this study was to assess patients' oxidative status during and after HD, and to clarify the relation between oxidative status and antioxidant solutes such as uric acid (UA) and ascorbic acid (AsA). Methods Serum diacron-reactive oxygen metabolites (d-ROM), and biological antioxidant potential (BAP), as well as serum concentrations of UA, AsA, urea nitrogen (UN), and creatinine (Cre) were measured in eight HD patients at six time points during and after HD. Inflow and outflow dialyzer blood was evaluated during HD or sham HD (no dialysate flow). Further, BAP was evaluated by adding UA or AsA to post-HD serum. Results No changes were found in d-ROM over time, whereas BAP was significantly decreased by HD. No differences were found in d-ROM during HD or sham HD, or between inflow and outflow blood. During HD, significantly lower BAP levels were found in outflow blood than in inflow blood. Serum UA and AsA levels were decreased by HD; however, no increases were obserbed in BAP levels after the addition of these molecules to post-HD serum. Conclusion These data indicate that HD reduces serum antioxidative capacity, and the loss of dialyzable molecules may be involved. However, this reduction in capacity does not seem to be caused by the loss of UA or AsA.     

Critical evaluation of plasma and LDL oxidant-trapping potential in hemodialysis patients.

BACKGROUND: We investigated whether the total peroxyl radical-trapping antioxidant potential (TRAP) assay, which has recently been proposed as a gauge of oxidative stress, could serve to evaluate plasma and low density lipoprotein (LDL) antioxidant state in hemodialysis (HD) patients. METHODS: TRAP was determined by the lag time of the chemiluminescence reaction induced by azo-initiator-catalyzed linoleic acid peroxidation in the plasma and corresponding LDL preparations of 23 HD patients and 22 healthy subjects. Antioxidant systems, including glutathione peroxidase (GSH-Px), ascorbate, vitamin E, and uric acid, oxidative stress markers including malondialdehyde (MDA), carbonyls, and advanced oxidation protein products (AOPP), and lipids, including cholesterol and triglycerides, were also determined in the plasma. RESULTS: Both plasma and LDL-TRAP were significantly increased in HD patients despite decreased GSH-Px and ascorbate and increased MDA, carbonyl, and AOPP plasma levels. Plasma TRAP values were closely related to both uric acid and AOPP levels, and LDL-TRAP values were related to triglycerides and AOPP levels. In vitro studies showed that: (a) plasma TRAP of control plasma increased regularly with supplementation of uric acid, although not reaching that of HD plasma with similar uric acid levels; (b) the addition of human serum albumin-AOPP also regularly increased control plasma TRAP, but was close to that of HD plasma with similar AOPP levels; and (c) LDL-TRAP was increased following LDL enrichment with triglycerides. CONCLUSION: Our study demonstrates that TRAP is not a relevant parameter for evaluating plasma or LDL antioxidant capacity in HD patients, due to the high plasma levels of uric acid, triglycerides and AOPP, which by themselves do not exert efficient antioxidant activity in vivo, but in vitro are able to scavenge the peroxyl radicals involved in the TRAP assay.