Serum malondialdehyde and prevalent cardiovascular disease in hemodialysis.

BACKGROUND: Oxidative stress has been proposed as a mechanism by which the accelerated rate of cardiovascular disease (CVD) observed in maintenance hemodialysis (HD) patients may be explained. This study examined the effects of HD and CVD on serum malondialdehyde (MDA) levels as a marker of oxidative stress in HD patients with and without prevalent CVD. Serum MDA levels and CVD prevalence in HD were modeled. METHODS: Serum MDA was determined using spectrophotometry in HD patients (N = 76, 53 men and 23 women, mean age 63.8 years) immediately prior to and at the conclusion of one midweek HD treatment. Traditional CVD risk factors, including serum lipids, lipoproteins, apolipoproteins, and fibrinogen, were also measured, as were serum chemistry and dialysis adequacy. RESULTS: Mean serum MDA levels were significantly elevated in HD patients with prevalent CVD compared with those without, whereas serum lipoprotein and plasma fibrinogen levels did not differ between the two groups. Patients in the highest compared with the lowest tertile of postdialysis MDA were nearly four times as likely to have prevalent CVD, and serum MDA was the single strongest predictor of prevalent CVD in this patient population. CONCLUSIONS: These findings indicate the presence of oxidative stress in HD patients, and are consistent with the theory of oxidative stress as a factor in accelerated CVD in this population.     

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.     

Lipid Peroxidation and Vitamin E in Red Blood Cells and Plasma in Hemodialysis Patients Under rhEPO Treatment

Abstract: Lipid peroxidation, measured by malonyldial-dehyde (MDA) and vitamin E in red blood cells (RBC) and plasma, was investigated in 25 hemodialysis (HD) patients before and after 6 months rhEPO therapy. RBC-MDA was significantly elevated, but plasma MDA was in the reference range. After recombinant human erythro-poietin (rhEPO) treatment, the MDA level was significantly decreased in both compartments. Marked vitamin E deficiency was established in RBC as well as in plasma. rhEPO therapy restored vitamin E levels in both compartments. Our data suggest a possible positive rhEPO-antioxidant effect in HD patients.     

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.     

Plasma pentraxin 3 is associated with cardiovascular disease in hemodialysis patients

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease

INTRODUCTION: Hypoalbuminemia is a powerful risk factor for cardiovascular mortality in hemodialysis patients (HD). Inflammation causes a decrease in albumin synthesis and an increase in albumin fractional catabolic rate, providing two mechanisms for hypoalbuminemia. The inflammatory response alters the endothelium and plasma protein composition in ways that favor vascular injury. Plasma volume is expanded in HD patients, providing another mechanism for hypoalbuminemia. Fibrinogen levels are an independent risk factor for cardiovascular disease (CVD) in HD patients, and fibrinogen levels are increased in HD patients. Plasma volume expansion is also an independent risk factor for CVD. METHODS: Albumin synthesis was measured in 74 HD patients as the disappearance of [125I] human albumin over six weeks. Fibrinogen was measured in plasma. Plasma fibrinogen mass was the product of fibrinogen concentration and plasma volume. RESULTS: Albumin synthesis correlated positively with plasma volume (P < 0.001). Fibrinogen concentration and plasma fibrinogen mass both correlated positively with albumin synthesis (P < 0.001). CONCLUSION: Albumin levels are reduced as part of the acute-phase response in HD. Plasma volume expansion also tends to decrease albumin concentration, but elicits an increase in its rate of synthesis, which, in turn, is associated with increased fibrinogen levels. Thus, both inflammation and plasma volume expansion factors that reduce albumin concentration and are independent cardiovascular risk factors, independently increase fibrinogen levels.     

Effect of 4-Week Treatment with Oral N-Acetylcysteine on Plasma Homocysteine Concentration and Antioxidant Activity of Patients on Chronic Hemodialysis

Plasma oxidative stress (OS) including total homocysteine (tHcy) and malondialdehyde (MDA) concentrations is usually elevated and antioxidant enzymes activities are decreased in patients suffering from chronic kidney disease. It is thought that OS in these patients may have a role in the pathophysiology of cardiovascular events. It has been suggested that N-acetylcysteine (NAC) may be effective to lower OS. This study was designed to evaluate the possible effect of 4-week treatment with oral NAC on plasma tHcy and MDA concentrations and status of antioxidant enzymes in chronic hemodialysis (HD) patients who were receiving vitamin B group at least from the onset of dialysis program. Twenty patients were enrolled in this study. All subjects were treated with oral NAC (600 mg twice daily) for 4 weeks. Predialysis plasma tHcy and MDA concentrations and activities of glutathione peroxidase, catalase, and superoxide dismutase were assessed before the initiation of NAC and after 4-week NAC therapy. At baseline, moderately severe hyperhomocysteinemia was present in about 63% of patients. The results showed significant (19%) decline in plasma tHcy concentration after NAC therapy. However, moderately severe hyperhomocysteinemia was persistently seen in about 50% of the patients. NAC did not affect concentration of MDA and antioxidant enzymes activities. Because of the proposed relationship between cardiovascular morbidity and hyperhomocysteinemia in patients on HD, daily supplementation of patients with NAC may be recommended as adjunct to vitamins in those subjects who did not respond adequately to group B vitamins alone.     

Evaluation of lipid peroxidation and erythrocyte glutathione peroxidase and superoxide dismutase in hemodialysis patients

Oxidative stress often occurs in chronic hemodialysis (HD). The aim of the present study was to determine plasma malondialdehyde (MDA) level for lipid peroxidation product and erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as enzymatic antioxidants. Thirty-one HD patients (aged 50.3 ± 14.9 years) who were dialyzed three times per week and 31 healthy subjects (aged 47.8 ± 13.9 years) were enrolled. The results showed lower enzymatic antioxidants activity (GPx, SOD) and higher MDA levels in comparison with control subjects. In addition, SOD and GPx activities significantly decreased and MDA increased after HD. We also found that there was a significantly negative correlation between SOD and GPx with MDA. The results suggest that elevated level of plasma MDA and reduced activities of SOD and GPx can be caused oxidative stress, which may play a critical role in HD complications.     

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.     

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.     

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.     

Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session

Background: The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1–7) (Ang-(1–7))/Mas axis, respectively.

Methods: There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119?HD patients with cardiovascular diseases (CVD) and 241?HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1–7) levels of the HD patients were determined.

Results: We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1–7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1–7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD.

Conclusions: Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1–7)/Mas axis activity in the circulation of HD patients with CVD.     

Plasma Pentraxin 3 is Associated with Cardiovascular Disease in Hemodialysis Patients

Abstract

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

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.     

Serum paraoxonase activity in uremic predialysis and hemodialysis patients

BACKGROUND: Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme and has been shown to reduce the susceptibility of low-density lipoprotein (LDL) to lipid peroxidation. This study aimed to investigate the activity and phenotype distribution of serum paraoxonase in uremic patients, and to evaluate the correlations of uremia-associated substances (urea, creatinine (Cr) and uric acid) with paraoxonase activity. METHODS: Twenty-eight patients with chronic renal failure (CRF), 44 patients with CRF undergoing hemodialysis (HD) and 26 healthy controls were included in this study. Paraoxon or phenylacetate was used as a substrate for measuring paraoxonase and arylesterase activity, respectively. The double substrate method was used to assign phenotypes. Serum lipid parameters were determined by routine laboratory methods. RESULTS: Paraoxonase activity, HDL-cholesterol and apolipoprotein (apo) AI levels were found to be significantly lower in HD patients than in controls. However, HDL-standardized paraoxonase activity (PON activity/HDL) was not different in the HD patients compared to controls. Arylesterase activity was significantly lower in both CRF and HD patients than in controls. Paraoxonase phenotype distribution was not different among the groups according to the double substrate method. Serum paraoxonase and arylesterase activities correlated inversely with serum urea and Cr levels. CONCLUSION: Patients on long-term HD have reduced paraoxonase/arylesterase activities and this could be related to reduced HDL-cholesterol and apo AI levels, as well as increased urea and Cr levels in uremia.     

Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients

BACKGROUND: Hyperhomocysteinemia, cardiovascular disease (CVD), and malnutrition are common in patients with end-stage renal disease (ESRD). This study was designed to assess possible relationships between total plasma homocysteine (tHcy), nutritional status, and ischemic CVD. METHODS: We performed a cross-sectional study in 117 unselected patients on maintenance hemodialysis (HD) treatment, among whom there was a high prevalence of malnutrition (56%), as assessed by the subjective global nutritional assessment (SGNA), and a high prevalence of CVD (60%), and prospectively, we followed-up the overall mortality for four years. RESULTS: The level of tHcy was elevated in 95% of the HD patients, and that of total plasma cysteine (tCys) was also significantly elevated, while the plasma concentrations of methionine (Met), serine (Ser), and taurine (Tau) were significantly lower than those in healthy controls. The 65 patients who were malnourished according to the SGNA score had significantly lower levels of serum albumin (SAlb), plasma IFG-1 (p-IGF-1), tHcy, tCys, and Met than the 52 patients with normal nutritional status, whereas the levels of Ser, Tau, plasma folate, and vitamin B12 were similar in the two groups. The prevalence of malnutrition was 30% in the 47 patients without CVD and was significantly higher (70%, P < 0.001) in the 70 patients with CVD, who also had lower tHcy, SAlb, plasma IGF-1, serum creatinine (SCr), and blood hemoglobin. The tHcy levels were positively correlated with SAlb, Met, tCys, and SCr. Stepwise, multiple-regression analysis showed that tCys, SAlb, and normalized protein equivalent of nitrogen appearance (nPNA), an indicator of protein intake, were independent predictors of tHcy. The patients with tHcy <24 micromol/L (median value) had a significantly worse four-year survival than those with a higher tHcy (> or =24 micromol/L). CONCLUSIONS: Our results demonstrate that most of HD patients have grossly elevated tHcy levels, but that the absolute level appears to be dependent on nutritional status, protein intake, and SAlb. The results also suggest that the lower tHcy levels in patients with CVD than in those without CVD may be related to the higher prevalence of malnutrition and hypoalbuminemia in the CVD patients. This is also in accordance with our observation that the patients with lower tHcy had a worse survival rate than those with higher tHcy, considering that malnutrition is a strong risk factor for mortality and that CVD is the most common cause of death in ESRD patients.     

Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients

AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.     

Oxidative stress markers and C-reactive protein in end-stage renal failure patients on dialysis

OBJECTIVE: The inflammatory status is a well-documented factor influencing the development of oxidative stress in dialysis patients. This study intends to evaluate the inflammatory activity and the plasma levels of total antioxidant capacity (TAC) and lipid peroxidation products in patients on peritoneal dialysis (PD), by comparison with hemodialysis (HD) patients. PATIENTS AND METHODS: Plasma concentration of TAC, lipid peroxidation products and C-reactive protein (CRP) were measured in 24 patients on PD, 32 HD patients (pre and post treatment) and 16 normal controls (NC). RESULTS: All patients had higher levels of TAC and lipid peroxidation products than NC (p < 0.001). Patients on PD, had similar levels to patients before HD but significantly higher (p < 0.001) than those post HD. The CRP concentration was higher in HD than in PD patients (p < 0.05). The percentage of patients with CRP > 10 mg/l was 48% in HD patients and 21% in PD patients. No correlation was observed between CRP and TAC nor CRP and MDA levels. CONCLUSIONS: We conclude that although PD and HD patients show an equal susceptibility in oxidative stress, CRP levels are higher in HD patients and this is indicative of a higher degree of inflammatory activity in these patients.     

Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease

BACKGROUND: The prevalence of increased oxidative stress and acute-phase inflammation in patients with chronic kidney disease (CKD) has not been thoroughly investigated. METHODS: Biomarkers of oxidative stress and acute-phase inflammation were measured in a cohort of 60 patients with stage 3-5 CKD compared to a healthy subject cohort. Levels of oxidative stress and inflammation were also compared to estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: All biomarkers of oxidative stress (plasma protein carbonyl group content, plasma free F2-isoprostane content, plasma protein reduced thiol content) and all markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6)] differed significantly between CKD patients and healthy subjects. There was no significant relationship between estimated GFR and any oxidative stress or inflammation biomarker. CRP levels were higher in patients with known coronary vascular disease (CVD) and in patients not taking angiotensin II inhibitors. Plasma IL-6 levels were significantly higher in patients with known coronary vascular disease and lower in patients taking statins. Biomarkers of oxidative stress were significantly higher in patients with diabetes and hypercholesterolemia. CONCLUSION: There is evidence of increased oxidative stress and acute-phase inflammation in patients with stage 3-5 chronic kidney disease compared to healthy subjects that does not closely correlate with estimates of GFR. Among CKD patients, inflammatory biomarkers correlate with known CVD and inversely correlate with the use of angiotensin II inhibitors and statins. A further increase in oxidative stress was noted in diabetic and hypercholesterolemic patients. Inflammation and oxidative stress may contribute to cardiovascular risk in CKD patients.     

Involvement of oxidative stress in the accelerated formation of pentosidine in patients with end-stage renal failure

SUMMARY: Advanced glycation end products (AGEs) have been found to accumulate in the amyloid deposits, skin and plasma of haemodialysis patients (HD), implicating the possible involvement of AGE-modified protein in pathogenesis in dialysis-related amyloidosis. Pentosidine, an AGE cross-link, is a specific marker for AGEs. Plasma pentosidine levels in HD patients were increased dramatically. In the present study, plasma pentosidine, fructoselysine, advanced oxidation protein products (AOPP) and glutathione peroxidase (GSHPx) levels were measured to elucidate the role of oxidative stress in pentosidine formation in nondiabetic HD patients. Plasma pentosidine did not correlate with fructoselysine; plasma AOPP levels were significantly higher than those in normal subjects (201.45 ± 57.93 vs. 55.91 ± 6.57 μmol/L, P <0.001) and correlated positively with plasma pentosidine in HD patients ( r =0.52, P <0.005); plasma GSHPx levels were significantly lower than those in normal subjects (168.40 ± 65.08 vs. 348.87 ± 86.10 U/I, P <0.001) and correlated negatively with plasma pentosidine ( r =0.54, P <0.001) in HD patients. Decreased GSHPx levels may lead to the accumulation of hydrogen peroxide. These findings implicate the involvement of oxidative stress in the accelerated formation of pentosidine in uraemia and suggest that pentosidine could be considered as an oxidative stress biomarker to estimate the degree of oxidative-stress-mediated protein damage.