Lipid peroxidation and antioxidant enzymes in children with chronic renal failure

Increased lipid peroxidation (LP) has been observed in dialysis patients and in predialysis adults with advanced chronic renal failure (CRF). The aim of this study was to investigate whether predialysis CRF children have increased LP in plasma and red blood cells (RBC) and to evaluate the activity of the antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] in RBC. Concentrations of selenium (Se), copper (Cu), and zinc (Zn)—cofactors of these enzymes—were determined both in erythrocytes and in plasma. LP was monitored by plasma and erythrocyte malonyldialdehyde (MDA) and by plasma organic hydroperoxide (OHP) concentrations. Forty-six predialysis children, aged 5–18 years, divided into two groups according to their serum creatinine levels [group I (n=14, mean serum creatinine 421.61±141.08 mol/l), group II (n=32, mean serum creatinine 174.94±45.50 mol/l)] and 27 age-matched healthy subjects were enrolled in the study. Significantly higher concentrations of plasma and erythrocyte MDA and plasma OHP, significantly lower activities of GSH-Px and CAT, and significantly lower concentrations of erythrocyte Se, Cu, and Zn and plasma Se and Cu were found in both groups of renal patients compared with controls. The SOD activity was reduced in both groups of CRF children. In group I the activity of SOD and GSH-Px was significantly lower than in group II. In summary, there is increased LP in plasma and RBC in children with predialysis CRF, even those patients with moderate renal insufficiency. The activity of the enzymatic antioxidant defense system is reduced in the RBC of predialysis patients. The antioxidant capacity is related to the severity of renal failure.     

Trace elements and lipid peroxidation abnormalities in patients with chronic renal failure

Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 +/- 0.12 vs. 1.05 +/- 0.13 mumol/l in controls; for erythrocyte GPX: 34.4 +/- 6.4 vs. 49.2 +/- 9 IU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p less than 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p less than 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p less than 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 +/- 0.26 vs. 2.55 +/- 0.15 mumol/l in controls and 2.79 +/- 0.40 mumol/l in the uremic group). The catalase activity was increased in HD patients (202 +/- 24 vs. 140 +/- 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.     

The association of oxidant–antioxidant status in patients with chronic renal failure

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p?相似文献   

Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl--glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.     

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.     

Low hair selenium and plasma glutathione peroxidase in children with chronic renal failure

Selenium (Se) is a trace element that incorporates into the selenoenzyme glutathione peroxidase (GSH-Px). There are conflicting results regarding the Se levels and activity of GSH-Px in adult uremic patients. The aim of this study was to determine (1) the hair Se status, (2) the possible relation between the hair Se status and the antioxidant enzyme, GSH-Px, and (3) the influence of different treatment procedures on hair Se status and GSH-Px activity in children with CRI, those treated conservatively and those on HD and on CAPD. Ninety-three patients, including 32 patients with CRI, treated conservatively, 42 PD patients, 19 HD patients and 34 healthy children were enrolled in the study. The hair Se level was measured by the atomic absorption spectrophotometer method. Plasma GSH-Px activity was determined using a Randox test combination (RANSEL). Hair Se levels were significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity was significantly lower in the CRI, CAPD, and HD groups when compared to the control group (P=0.001, P=0.001, and P=0.001, respectively). Plasma GSH-Px activity correlated with the GFR in patients with CRI and the control group (P=0.000; r²=0.60). There was no correlation between plasma GSH-Px and hair Se levels in the patient and control groups. These results revealed a decreased hair Se level and impaired antioxidative capacity in children with CRI on CAPD and HD. The lack of any relation between plasma GSH-Px and hair Se suggests that plasma GSH-Px is not a good marker of Se stores.     

胃癌患者超氧化物歧化酶,丙二醛与红细胞免疫功能变化的初探

为初步探讨胃癌患者超氧化物歧化酶、丙二醛与红细胞免疫功能变化的关系,通过对31例胃癌患者手术前后红细胞C_(3b)受体活性、红细胞超氧化物歧化酶(SOD)、红细胞丙二醛(E-MDA)、血浆丙二醛(P-MDA)等指标的动态观察发现,术前红细胞C_(3b)受体活性、E-SOD以及E-SOD/E-MDA明显降低,E-MDA、P-MDA升高,红细胞C_(3b)受体活性与E-SOD、E-SOD/E-MDA正相关而与E-MDA负相关。胃癌根治术后14天,红细胞C_(3b)受体活性及E-SOD、E-MDA等指标均迅速恢复。推测胃癌时氧自由基堆积所致脂质过氧化损伤是机体红细胞免疫功能低下的重要原因,应用自由基清除剂可望提高机体红细胞免疫功能。     

Superoxide Dismutase and Catalase Activities in Patients Undergoing Hemodialysis and Continuous Ambulatory Peritoneal Dialysis

In this study, superoxide dismutase (SOD) and catalase activities were determinated in the erythrocytes (RBC) from patients with chronic renal failure. The study included healthy subjects (n = 7), patients on hemodialysis (HD) using polyacrylonitrile-type dialysis membrane (before and after HD) (n = 10), patients on HD using cuprophane-type dialysis membrane (before and after HD) (n = 6), and patients on continuous ambulatory peritoneal dialysis (CAPD) (n = 11). A significant decrease in SOD activity was found in HD groups using polyacrylonitrile- or cuprophane-type dialysis membrane. SOD activity was found to increase in patients undergoing CAPD. We have found that CAT activity is higher in all the CRF groups in respect to the control: with polyacrylonitrile-type dialysis membrane, with cuprophane-type dialysis membrane, and in CAPD treatment.     

Effect of intravenous iron sucrose on oxidative stress in peritoneal dialysis patients

AIM: Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. METHODS: Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. RESULTS: Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 +/- 66.69 to 123.68 +/- 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100-400 and 400-800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. CONCLUSION: There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.     

Oxidative stress during dialysis: effect on free radical scavenging enzyme (FRSE) activities and glutathione (GSH) concentration in granulocytes

Background. Living cells are protected by free radical scavenging enzymes against oxygen radical-mediated damage. It has been suggested that granulocytes are activated on the surface of dialyser membranes, resulting in the generation of free radicals. We have recently reported a lack of plasma lipid peroxidation and unchanged glutathione peroxidase (GSH-Px) as well as glutathione reductase (GSSG-R) activities in red blood cells of haemodialysis patients. However, because mature red cells are free of DNA and RNA, free radical scavenging enzymes (FRSE) cannot be regulated on the gene level in response to an acute oxidative stress. In contrast to erythrocytes, granulocytes are nucleated cells and FRSE protein concentrations can therefore be modulated. Methods. GSH-Px, GSSG-R, superoxide dismutase (SOD) activities and total glutathione (GSH) were determined spectrophotometrically using a Cobas Fara semi-automatic analyser in granulocytes of 31 healthy blood donors and in 28 patients with chronic renal failure (CRF) for more than 6 months before as well as immediately after a single dialysis treatment. Patients were treated either by haemodialysis (n=17) using low-flux polysulphone membranes or by haemofiltration (n=11) using high-flux polysulphone membranes. Results. Compared to healthy controls, SOD and GSSG-R activities were increased in granulocytes of HD and HF patients, GSH and GSH-Px were decreased before a single treatment. After dialysis SOD and GSH-PX activities were significantly induced by both HD and HF whereas GSSG-R activities and GSH were decreased. Conclusions. These results show that the enzymatic defence against oxygen radicals can be induced in granulocytes of patients undergoing regular dialysis treatment, whereas the non-enzymatic defence is compromised as shown by decreased GSH concentrations, both suggesting increased oxidative stress.     

Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine A and tacrolimus-based regimens

BACKGROUND: Oxidative stress is one of the leading causes of cardiovascular morbidity and mortality in chronic kidney disease. Although it is clear that many metabolic abnormalities improve, the effects of kidney transplantation on oxidative state are obscure. METHODS: Twenty-three kidney transplant patients were included in the study. Eleven patients (mean age 27.9+/- 9.1 years) were treated with cyclosporine A (CsA) whereas 12 patients (mean age 22.4 +/- 3.4 years) were treated with tacrolimus. Twenty-three healthy subjects served as controls. None of the patients or controls suffered from diabetes mellitus or an acute infection at the time of the study. Plasma malondialdehyde (MDA), plasma selenium (Se), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), erythrocyte Zn (EZn), and erythrocyte Cu (ECu) levels were studied before and in the 1st, 3rd, 7th, 14th and 28th days after the transplantation. RESULTS: The GSH-Px, SOD, ECu, EZn and selenium levels were lower and MDA levels were higher in patients than controls before transplantation (p < 0.001 for all). MDA levels decreased and SOD, GSH-Px, ECu, EZn levels increased in parallel to the decrement of serum creatinine levels following the renal transplantation. No difference was found among the patients regarding the treatment regime. CONCLUSION: The study data suggest that the improvement in oxidative state parameters begins at the first day of renal transplantation and continues at the 28th posttransplant day in living donor transplantations.     

Reduction of left ventricular hypertrophy in children undergoing hemodialysis

Left ventricular hypertrophy (LVH) is related to a 1,000-fold increased risk of cardiovascular morbidity and mortality in young adults with end-stage renal disease (ESRD) treated with hemodialysis (HD) or peritoneal dialysis. We report a series of 17 children (5 girls, 12 boys), with a median (range) age of 11 (2–18) years, all treated by HD, who presented with an increased left ventricular mass (LVM) index of 54.8±4.5 g/m^2.7 at onset of HD and reached 36.2±2.6 g/m^2.7 (mean±SEM, P<0.0001) at last follow up. Over the observation period, systolic (P<0.0001) and diastolic (P<0.0001) blood pressure (indexed for height, gender, and age) decreased and hemoglobin (+2.8 g/dL; P<0.0001) increased compared to initial values. Only BP as well as plasma protein level at onset of HD session correlated with LVM in multiple correlation analysis. In conclusion, increased LVM is a common feature in pediatric patients with ESRD. Normalization of BP and reduction of the extracellular volume (represented by plasma protein at onset of HD session) are key points in reducing LVH during HD in children.     

Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells.

BACKGROUND: Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions. METHODS: We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session. RESULTS: Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa. CONCLUSIONS: Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.     

Myeloperoxidase serves as a marker of oxidative stress during single haemodialysis session using two different biocompatible dialysis membranes.

BACKGROUND: There is increased oxidative stress in patients undergoing haemodialysis (HD); however, little is known of how different dialysis membranes contribute to the oxidative stress induced by the dialysis procedure per se. We therefore studied the influence of two different dialysis membranes on oxidative stress during HD. METHODS: Eight patients undergoing HD three times per week were enrolled in this cross-controlled study. Patients sequentially received HD using polysulphone (PS) and regenerated cellulose (RC) dialysis membranes for 1 week each. Blood samples were collected in the last section of each hollow fibre 0, 15, 120 and 240 min after starting HD. We determined superoxide anion production derived from neutrophils, superoxide dismutase (SOD) and glutathione peroxidase (GPx) derived from washed red cells, plasma myeloperoxidase (MPO), plasma thiobarbituric acid-reactive substances (TBARS), plasma advanced oxidation protein products (AOPP) and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: Leukocyte numbers, including neutrophils, lymphocytes and monocytes, decreased significantly after 15 min of dialysis, more so with RC than with PS membrane. For both membranes, superoxide anion production transiently increased during the first 15 min whereas the post-dialysis production was decreased. Plasma MPO levels persistently increased during dialysis with the two membranes. Moreover, the increase was more marked with RC than with PS membrane. AOPP and 8-OHdG levels increased progressively when using RC membranes. There were no significant differences in SOD, GPx, TBARS, AOPP and 8-OHdG levels between the two membranes. CONCLUSIONS: The biocompatibility of the dialyser affects oxidative stress production during a single dialysis session. The measurement of MPO may serve as a reliable marker of the degree of oxidative stress induced using dialysis membranes of different biocompatibilities.     

The effects of intravenous iron treatment on oxidant stress and erythrocyte deformability in hemodialysis patients

BACKGROUND: It is well known that free iron causes oxidant stress to increase. However data concerning whether intravenously (I.V) administered iron in maintenance doses (10-20 mg) gives rise to increased oxidant stress and disturbed erythrocyte deformability (EDEF) in hemodialysis (HD) patients is lacking. In the present study, we aimed to evaluate and compare the effects of I.V iron on oxidant stress and EDEF. PATIENTS AND METHODS: Thirteen HD patients (10 males, 3 females, mean age: 49.9 +/- 13.4 years), given I.V iron were included in the study. All patients were undergone three consecutive HD session. The first HD session was performed without iron administration (Group 1), whereas in the following sessions the same patients were given 20 mg (Group 2) and 100 mg (Group 3) iron III hydroxide sucrose (Venofer--Abdi Ibrahim) I.V at the end of the dialysis session. In study periods, 7 blood samples were drawn from each patient: before dialysis, at the end of the dialysis (just after the session), 15, 30, 60, 90 and 120 minutes after each dialysis session. However 15 minute samples were not drawn in the third group, since I.V iron was given by infusion in 30 minutes. EDEF and plasma malondialdehyde (MDA) were studied in all samples. RESULTS: When the results of the session without iron were considered, bivariate correlation analysis did not reveal any correlation between MDA and EDEF. When the course of each parameter were considered separately, MDA levels 90 and 120 minutes after HD session were significantly higher than that of the before and just after the HD session (p < 0.05). Whereas EDEF in 60, 90 and 120 minutes after HD session was found to be worsened when compared to before and just after HD sessions' values (p < 0.05). When results of the session with 20 mg iron were considered, EDEF and MDA values were not found to be correlated and throughout the course. Although EDEF did not present any significant change, MDA levels 60, 90 and 120 minutes after HD session were found to be significantly higher than that of the 15 and 30 minutes after HD session (p < 0,05). When results of the session with 100 mg iron were considered, MDA levels 30, 60, 90 and 120 minutes after HD session were found to be significantly higher than that of the before and just after the HD sessions' (p < 0,05). EDEF in 90 and 120 minutes after HD session was improved and no correlation between MDA and EDEF was observed. When groups were compared with each other, plasma MDA levels in session with 100 mg iron at the beginning, at the end and 30 minutes after HD were significantly lower than that of the without iron group (p < 0.05). Similarly MDA levels in session with 100 mg iron at the beginning, at the end, 30 minutes and 120 minutes after HD were significantly lower than that of the 20 mg iron (p < 0.05). When EDEF values in sessions with 20 mg iron and without iron were considered, only values 60 and 90 minutes after dialysis were significantly improved in 20 mg iron group. The others were statistically similar. CONCLUSION: In the present study, it was observed that I.V administered iron in 20 and 100 mg doses did not cause additional deteriorating effect on oxidant stress and EDEF was even improved by I.V iron.     

Elevated plasma F2-isoprostanes in patients on long-term hemodialysis

BACKGROUND: End-stage renal disease (ESRD) patients on long-term hemodialysis (HD) may be under increased oxidative stress, caused by either HD or renal failure. Plasma F2-isoprostanes have been established as an important indicator of in vivo oxidative stress. METHODS: Plasma esterified F2-isoprostanes were measured in 25 HD patients and 23 controls with normal renal function, employing gas chromatography-mass spectrometry with negative chemical ionization (GC-MS-NCI). C-reactive protein (CRP) was determined concurrently in patients and controls by enzyme-linked immunosorbent assay (ELISA). alpha-Tocopherol, retinol, albumin and creatinine were also determined. RESULTS: The average total esterified F2-isoprostanes in the ESRD patients was 1.62 +/- 0.73 vs. 0.27 +/- 0.10 ng/mL in controls (P < 0.001), with no overlap between patients and controls. Plasma F2-isoprostanes in diabetic ESRD patients were similar to F2-isoprostanes in patients with other causes for renal failure. In a subset of 10 of these ESRD patients evaluated eight months after the initial measurement, plasma-esterified F2-isoprostanes were not altered by an individual dialysis session. Average plasma CRP values were also higher in HD patients (P < 0.02), but some patients had CRP values that were similar to controls. In the HD patients, total plasma F2-isoprostanes and plasma CRP were correlated (r = 0.48, P = 0.015). Plasma alpha-tocopherol did not differ between patients and controls, but plasma retinol was higher in patients (3.15 +/- 1.71 micromol/L) than in controls (1.97 +/- 0.51 micromol/L, P < 0.05). CONCLUSIONS: These results are consistent with the hypothesis that oxidative stress in ESRD patients contributes to increased values of esterified plasma F2-isoprostanes, with concurrent increases in plasma CRP levels in some patients. Impaired clearance of esterified F2-isoprostanes may contribute to the elevated levels in renal failure. Plasma esterified F2-isoprostanes may be a useful indicator to evaluate effectiveness of interventions to decrease oxidative stress and associated inflammation.     

Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients

Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival. We explored whether electrolyte-reduced water (ERW) could palliate HD-evoked erythrocyte impairment and anemia. Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic HD patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or ERW treatment (n=15) during an HD course. The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after HD without any treatment. HD resulted in decreased plasma VC, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb. Antioxidants treatment significantly palliated single HD course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order VC>ERW>VE-coated dialyzer. However, ERW had no side effects of oxalate accumulation easily induced by VC. Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients.     

Oxidative stress, inflammation and early cardiovascular damage in children with chronic renal failure

The relationship between inflammation, oxidant stress and cardiovascular damage in children with chronic renal failure (CRF) has not previously been investigated. The aim of this study was to investigate markers of oxidative stress, inflammation and early cardiovascular abnormalities. Therefore, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; blood glutathione (GSH) and serum malondialdehyde (MDA) levels; C-reactive protein (CRP) and proinflammatory cytokines (IL-6, TNF-α,); and left ventricular masses (LVM) and intima media thicknesses (IMT) were measured in children with CRF. A total of 29 children with CRF (19 nondialysis, 10 peritoneal dialysis) were included. The control group consisted of 25 healthy subjects. CRF children had significantly increased IL-6, TNF-α, CRP and MDA concentrations and decreased SOD, CAT and GSH levels compared with controls (P<0.05). Nondialysis and peritoneal dialysis subgroups had similar oxidative stress and inflammation biomarkers (P>0.05). Erythrocyte CAT was positively correlated with CRP, TNF-α, and IL2-R in the study group. Positive correlations were found between cytokine concentrations, CRP and urea/creatinine levels. Significantly increased LVM and IMT values were found in CRF children (P<0.05). In conclusion, increased oxidant stress and inflammation together with early cardiovascular damage were found in CRF children. Further studies with more patients are needed to verify these results.     

Hemodialysis does not influence the peroxidative state already present in uremia

Hemodialysis (HD) patients are exposed to high oxidative stress, however, the nature of this stress is still unclear. In this study, we employed a specific lipid peroxidative product, phosphatidylcholine hydroperoxide (PCOOH), and evaluated the peroxidative effect of end stage renal disease by measuring thiobarbituric acid reactive substances (TBARS) and PCOOH in both plasma and erythrocyte membrane. We also surveyed plasma TBARS and PCOOH before and after HD sessions thereby assessing oxidative stress by a single HD procedure. The plasma TBARS level of healthy controls was 2.9 +/- 0.4 nmol/ml. Those of HD patients before and after HD session were 5.1 +/- 1.4 and 3.1 +/- 0.5 nmol/ml, respectively, and the pre-HD plasma TBARS levels were significantly higher than those of controls and after HD. The plasma PCOOH concentration of patients before HD was 119.7 +/- 58.4 pmol/ml and was significantly higher than that of controls which was 88.6 +/- 14.3 pmol/ml. After HD, the plasma PCOOH level decreased to 103.2 +/- 36.0 pmol/ml, which was still significantly higher than that of controls. In erythrocytes, the PCOOH level of patients was 259.3 +/- 105.4 nmol/g RBC and was significantly higher than that of controls with 88.6 +/- 32.0 nmol/g RBC. Analyzed with respect to the cause of renal disease, the polycystic kidney disease patients showed significantly lower plasma PCOOH levels than the others. These results suggest that there is an increase of lipid peroxidation in both plasma and erythrocytes of HD patients, though this oxidative stress was not brought about by HD.