Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.

BACKGROUND: Cardiovascular diseases are the leading cause of death in haemodialysis patients. Hyperhomocysteinaemia is an independent risk factor. Basic research has provided strong evidence that oxidation of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Oxidative stress, lipid metabolism alterations, and hyperhomocysteinaemia observed in haemodialysis patients could induce increases in LDL oxidation. This study was designed to determine the effect of folinic acid on hyperhomocysteinaemia and to assess the antioxidant efficacy of folinic acid. The antioxidant effect of folinic acid was compared with that of vitamin E. METHODS: Sixteen stable patients (11 men, five women; mean age 54.3+/-6.32 years) on standard haemodialysis received 400 mg of vitamin E, orally, at the end of each haemodialysis session for 3 months. After a 1-month wash-out, they received 10 mg of folinic acid, intravenously, at the end of each haemodialysis session for an additional 3 months. Blood samples were drawn in the morning after an overnight fast and before dialysis. Plasma vitamin E was analysed by high-pressure liquid chromatography. Malondialdehyde (MDA) was determined using a fluorimetric method and plasma copper oxidized anti-LDL antibodies (Ab-LDLox) were measured with an ELISA method using native LDL and oxLDL as antigens. Plasma homocysteine was determined by an FPIA method. RESULTS: Folinic acid supplements significantly reduced hyperhomocysteinaemia (-44%), MDA concentrations (-40%), and IgG-LDLox titres (-13%). CONCLUSIONS: Treatment with folinic acid lowers plasma homocysteine levels and, like vitamin E, affords antioxidant protection, which prevents lipid peroxidation. This lowering of lipid peroxidation may reduce the risk of atherosclerosis and prevent or delay cardiovascular complications in HD patients.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis

Intravenous iron application to anemic patients on hemodialysis leads to an "oversaturation" of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC0-180 min) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma alpha-tocopherol concentrations (27.6 +/- 1.8 micromol/L) and ratios of alpha-tocopherol to cholesterol (5.88 +/- 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 +/- 0.28 micromol/ L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly (P < 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 +/- 0.075 x BDI). Vitamin E supplementation, leading to a 68% increase in plasma alpha-tocopherol concentrations, significantly reduced the AUC0-180 min of MDA to cholesterol (P = 0.004) and peroxides to cholesterol (P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.     

Lipid peroxidation and antioxidant enzymes in children on maintenance dialysis

End-stage renal disease (ESRD) is associated with numerous complications, which may partly result from excessive amounts of reactive oxygen species and/or decreased antioxidant activity. The aim of the study was to evaluate lipid peroxidation (LP) in plasma and erythrocytes, erythrocyte antioxidant enzyme activity (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GSH-Px), and concentrations of Cu and Zn as cofactors of SOD and Se as a cofactor of GSH-Px in erythrocytes, plasma and in dialysis fluid in children with ESRD. In particular, we analyzed whether the modality of dialysis could modify oxidative stress parameters in children. To determine the influence of hemodialysis (HD) on oxidative stress, the measurements were also performed on HD children 20 min after the beginning of the dialysis session. Thirty-one patients participated in the study: group I with 10 children on continuous ambulatory peritoneal dialysis (CAPD), and group II with 21 on HD. The erythrocyte malondialdehyde concentrations (E-MDA), plasma MDA (P-MDA) and plasma organic hydroperoxide (OHP) in children from both groups were higher than in controls. E-MDA and P-MDA in HD before the session was lower compared to the values after 20 min of HD session (time T²⁰). The activity of SOD, GSH-Px, CAT, concentrations of erythrocyte and plasma Se, Cu, Zn were lower in children with ESRD than in controls. In the HD group, the activity of GSH-Px, CAT, and levels of trace elements in erythrocytes and in plasma were diminished at time T²⁰. In conclusion, increased oxidative stress occurs in children on maintenance dialysis, independent of dialysis modality. The activity of the enzymatic antioxidant defence system is highly reduced in red blood cells of pediatric dialysis patients. Children with ESRD exhibit lower trace element (Se, Cu, Zn) levels in plasma and erythrocytes as compared to healthy subjects. Oxidative stress is aggravated during every single HD session in children.     

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.     

N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients--a pilot study

BACKGROUND: Oxidative stress has been implicated in the development of endothelial damage in hemodialysis (HD). We have assessed the effects of N-acetylcysteine (NAC), a compound with antioxidant effects, on malondialdehyde (MDA), a marker of oxidative stress on lipid peroxidation. METHODS: A clinical trial was conducted in which 24 chronic HD patients were divided into 2 groups according to gender, age, time on HD and cause of renal failure. The NAC group (n = 12) received 600 mg of NAC twice a day for 30 days. The remaining patients constituted the control group (n = 12). MDA levels were measured pre- and post-dialysis at the beginning of the study (baseline) and on day 30 (30 days). RESULTS: Baseline pre- and post-dialysis MDA levels were not different between both groups and were above normal values. A significant decrease was found in the NAC group when either pre- or post-dialysis MDA levels were compared to the corresponding control group levels on day 30 (pre-dialysis NAC vs control group 3.01 +/- 0.6 vs 4.5 +/- 0.73 micromol/l, p < 0.0001, post-dialysis NAC vs control group 2.76 +/- 0.5 vs 4.39 +/- 0.7 micromol/l, p < 0.0001). Only in the NAC group were pre-dialysis MDA 30-day levels different from pre-dialysis baseline levels (3.01 +/- 0.6 vs 5.07 +/- 1.6 micromol/l, p < 0.002). Post-dialysis MDA 30-day concentrations were significantly lower than post-dialysis MDA baseline levels (2.76 +/- 0.5 vs 4.32 +/- 0.7 micromol/l, p < 0.002) and pre-dialysis MDA 30-day measurements (2.76 +/- 0.5 vs 3.01 +/- 0.6 micromol/l, p < 0.011). CONCLUSIONS: MDA levels are elevated in chronic HD patients and are not significantly reduced by HD. NAC significantly reduces malondialdehyde levels in chronic HD patients.     

Expression of scavenger receptor CD36 in chronic renal failure patients

BACKGROUND: Patients with chronic renal failure (CRF) are at increased risk of atherosclerosis development. One of the major steps in pathogenesis of atherosclerosis is formation of foam cells. Scavenger receptor CD36 is among the major receptors for oxidized low density lipoproteins (oxLDL) and therefore it plays a crucial role in foam cell formation. The aim of the present study was to investigate the expression of CD36 on blood monocytes of CRF patients. METHODS: Expression of CD36 on blood monocytes of CRF patients treated with hemodialysis (HD), peritoneal dialysis (PD), those not yet on dialysis (predialysis), and controls was assessed with the use of flow cytometry. Additionally, the major lipid peroxidation markers, malondialdehyde (MDA) and 4-hydroxyalkenals (HAE), were measured. Further, impact of treatment with HMG-CoA reductase inhibitors (statins) on CD36 expression in CRF patients was evaluated. RESULTS: Expression of monocyte CD36, measured as mean fluorescence intensity (MFI) was significantly higher in HD and PD patients, when compared to controls without renal insufficiency (respectively: 1011 +/- 288 and 1000 +/- 309 vs. 710 +/- 313; P < 0.01 for both groups). This was not the case in predialysis group (828 +/- 363 vs. 710 +/- 313). Higher concentrations of lipid peroxidation indicators, MDA and HAE were observed in all three subgroups of CRF patients (2.1 +/- 0.51, 2.02 +/- 0.27, and 1.81 +/- 0.53 microm in HD, PD, and predialysis group, respectively, vs. 1.13 +/- 0.59 microm in controls; P < 0.01). Patients treated with statins showed significantly lower CD36 expression than patients without statin therapy. CONCLUSIONS: The present study, for the first time, demonstrates increased expression of CD36 scavenger receptor in CRF patients. This may be a possible risk factor for accelerated atherogenesis observed in this group of 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.     

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.     

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.     

Levels of serum ascorbate and its metabolites in hemodialysis patients

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.     

Dialysis filter type determines the acute effect of haemodialysis on endothelial function and oxidative stress.

BACKGROUND: Endothelial function of large arteries is impaired in chronic haemodialysis patients and oxidative stress due to the dialysis procedure has been suggested as a causal factor. However, it is not clear whether different types of dialysis membranes affect endothelial function differently. Therefore we determined endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery as well as markers of oxidative stress immediately before and after haemodialysis (HD) with either a cellulosic cuprophane or a synthetic polysulphone dialyser in a blinded, randomized, cross-over study. METHODS: Twelve haemodialysis patients (age 55+/-3 years, time on dialysis 20+/-2 months, mean fluid change -1782+/-21 ml, systolic/diastolic blood pressure 139/75 mmHg) were included. Using a multi-gate-pulsed Doppler system (echo-tracking device) brachial artery FMD and nitroglycerine-induced, endothelium-independent vasodilatation (NMD) were measured. Patients were randomized to HD with either a polysulphone or a cuprophane membrane and were crossed over to the other filter. Investigators were blinded to the type of membrane used. Serum concentrations of oxidized LDL (oxLDL) and alpha-tocopherol as markers of oxidative stress were measured before and after each dialysis session. RESULTS: Data are given as mean+/-SEM. Treatment with polysulphone filter HD did not significantly affect FMD (baseline 9.3+/-2.0% vs after HD 9.6+/-1.8%). After dialysis with a cuprophane membrane FMD decreased from 9.4+/-2.1 to 7.4+/-1.8% (P<0.05). NMD was not significantly affected by HD irrespective of the membrane material used. Serum levels of oxLDL were not changed by either treatment; however, alpha-tocopherol concentrations fell significantly after dialysis with the cuprophane filter (baseline 18.0+/-2.3 after HD 16.6+/-1.3 micro g/ml, P<0.05), while alpha-tocopherol levels remained unchanged when the polysulphone membrane was used. CONCLUSIONS: The type of dialysis filter membrane determines the acute effect of haemodialysis on arterial endothelial function. Differences in biocompatibility and oxidative stress may account for the observed differential effects, since the decrease of FMD after dialysis with a cellulosic cuprophane membrane-but not with a synthetic polysulphone membrane-was associated with a reduction in serum vitamin E.     

Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.

BACKGROUND: Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). METHODS: We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. RESULTS: A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. CONCLUSIONS: These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss.     

Effect of dialysis type on serum lipids, apolipoproteins, and lipoproteins

AIM: Dyslipidemia is common among patients with end-stage renal disease, whether treated by hemodialysis (HD) or peritoneal dialysis (PD). However, there are not enough data about the effect of dialysis type on serum lipoprotein (a) [Lp(a)], apolipoprotein (a) [Apo(a)], apolipoprotein (b) [Apo(b)], and lipid levels. The aim of this study was to determine the effect of dialysis type on serum lipid levels. MATERIALS AND METHODS: This study enrolled 40 HD patients (20 men and 20 women, aged 48.1 +/- 17.6 years) and 69 PD patients (35 men and 34 women, aged 45.2 +/- 16.3 years). Serum lipid profile including total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), Apo(a), Apo(b), and Lp(a) were determined in HD and PD patients. Patients who have used statins within the last six months were not included in the study. RESULTS: No significant differences in TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), or Lp(a) serum levels were found between HD and PD patients. Serum TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), and Lp(a) in HD and PD patients were 172.2 +/- 42.7 (mg/dL) vs. 181.0 +/- 53.0 (mg/dL), 97.2 +/- 36.2 (mg/dL) vs. 101.4 +/- 33.6 (mg/dL), 45.3 +/- 11.9 (mg/dL) vs. 41.4 +/- 11.1 (mg/dL), 144.7 +/- 71.8 (mg/dL) vs. 173.0 +/- 76.8 (mg/dL), 1.2 +/- 0.5 (g/L) vs. 1.0 +/- 0.2 (g/L), 0.9 +/- 0.3 (g/L) vs. 1.2 +/- 0.3 (g/L), and 43.1 +/- 40.6 (mg/dL) vs. 46.0 +/- 42.7 (mg/dL), respectively. CONCLUSION: The results of this study show that the maintenance CAPD treatment is associated with more pronounced alterations of the lipoproteins and lipid metabolism than those observed during HD treatment.     

Cytotoxic effects exerted by polyarylsulfone dialyser membranes depend on different sterilization processes

Polyarylsulfone group is one of the most important polymeric materials used in the biomedical field, due to its excellent properties, such as good thermal, chemical, and mechanical stability. There are three important polyarylsulfone polymers, all of which have excellent electrical properties: polysulfone (PSu), polyarylsulfone (PAS) and polyarylethersulfone (PAES). All these polymers have excellent creep, radiation and high temperature resistance. In this study, we aimed to determine the effect of three sterilization processes (steam, ethylene oxide and gamma rays) on cytotoxicity of polyarylsulfone dialysis membranes. Ten long-term dialysis patients and ten age-matched healthy controls were enrolled in our study. We analysed (1) serum effect on cultured endothelial cell viability using MTT assay and (2) lipid peroxidation assessed by serum malondialdehyde (MDA) formation at the beginning (T0), the middle (T2) and the end (T4) of haemodialysis (HD) session. Our results clearly showed that steam-sterilized membranes improve endothelial cell viability when compared to ethylene oxide or gamma rays-sterilized ones. Moreover, there is a increased generation of MDA in patients sera during HD session. The serum MDA concentration was about 3, 6 and 10 times higher, respectively, for steam, ethylene oxide and gamma rays sterilization procedures when compared to the MDA amount in healthy subject sera. We concluded that using steam instead of ethylene oxide or gamma rays for sterilization may improve the biocompatibility of polyarylsulfone membranes.     

Circulating concentrations of soluble interleukin 6 receptors gp80 and gp130 in chronic renal failure and effects of renal replacement therapy

BACKGROUND: Circulating receptors modulate the biological effects of cytokines. Renal insufficiency is known to influence the concentrations of the soluble tumor necrosis factor (TNF) receptors p55 and p75. No data are available on the concentrations of the circulating interleukin 6 (IL-6) receptors gp80 and gp130 during chronic renal insufficiency. METHODS: We compared the serum concentrations of the IL-6 receptors gp80 and gp130 to those of the TNF receptors p55 and p75 in end-stage chronic renal failure, continuous ambulatory peritoneal dialysis, and hemodialysis (HD). RESULTS: In healthy controls the concentrations of gp80, gp130, p55, and p75 in serum were 82.1 +/- 24.3, 87.9 +/- 20.2, 1.1 +/- 0.2, and 1.7 +/- 0.3 ng/ml, respectively. These concentrations were increased to, respectively, 112.2 +/- 18.0, 186.0 +/- 37.7, 10.5 +/- 4.3, and 15.0 +/- 7.5 ng/ml in chronic renal failure, to 138.8 +/- 18.0, 181. 3 +/- 46.1, 25.5 +/- 5.2, and 19.1 +/- 3.4 ng/ml in continuous ambulatory peritoneal dialysis, and to 107.9 +/- 29.4, 146.6 +/- 30. 5, 22.9 +/- 6.3, and 16.8 +/- 6.0 ng/ ml in HD (before dialysis session). The concentrations after HD were higher for p75 only. CONCLUSIONS: The data show that the concentrations of the IL-6 receptors (gp80 and gp130) are elevated in chronic renal insufficiency. The increase is relatively low as compared with the elevation of the TNF receptors in this situation. HD does not result in a consistent change in serum concentrations of the various receptors. Copyright Copyright 1999 S. Karger AG, Basel     

Brain natriuretic peptide and its relationship to left ventricular hypertrophy in patients on peritoneal dialysis or hemodialysis less than 3 years

An increase of brain natriuretic peptide (BNP) levels is commonly observed in patients on dialysis. Increased circulating levels of BNP are related to future cardiac events and associated with shorter survival in patients on chronic hemodialysis (HD). During the first 1 or 2 years on dialysis, patients on peritoneal dialysis (PD) have been shown to have an improvement in left ventricular hypertrophy, blood pressure, and volume status. This study compares BNP levels and cardiac status of PD and HD patients without cardiovascular disease and on dialysis for less than 36 months. The correlation between plasma BNP concentration and findings of echocardiography before HD scans were examined and compared with findings of PD. Twenty-two HD patients (15 men, 7 women; mean age, 52.5 +/- 13.9 years) and 19 PD patients (10 men, 9 women; mean age, 47.6 +/- 11.3 years) were studied. There were no significant differences between HD and PD patients with regard to age, gender, duration of dialysis, left ventricular mass, left ventricular mass index (p > 0.05). Plasma BNP levels were markedly greater in HD patients (467.8 +/- 466.5 pg/ mL) than those of PD patients (143.1 +/- 165.2 pg/mL). Urine output was significantly higher in PD patients compared with HD patients (p < 0.05). A positive correlation between systolic blood pressure, diastolic blood pressure, and plasma BNP in HD patients (r: 0.653, p: 0.001; r: 0.493, p: 0.023, respectively) was detected. Additional studies are needed to investigate whether lower BNP level in PD patients is an advantage.