Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy.

INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia. CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease. CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.

Improved quality of samples and laboratory turnaround time using 3.5 mL low vacuum BD Vacutainer® Barricor tubes in the emergency department.

BACKGROUND: Centrifugation is a consuming time step which participates to increase the turnaround time (TAT) in laboratories, likewise hemolysis sample that needs a re-sampling could delay management of patients. Recently, it has been postulated that BD Barricor™ tube could allow to decrease the centrifugation time and prevent hemolysis, two key feature to ensure high-quality results.Aim of the study was to evaluate the impact of replacing 4 mL BD vacutainer heparin lithium tube by low vacuum 3.5 mL BD vacutainer Barricor™ tube in an emergency department (ED) on hemolysis rate and TAT. METHODS: Data of hemolysis index (HI) and TAT were compared between the first period of 15 days using 4 mL BD vacutainer heparin lithium tubes with 15 min at 2000xg as centrifugation setting and a second period of 15 days using BD vacutainer Barricor™ tube centrifuged 3 min at 4000xg. RESULTS: A significantly reduced time duration between reception of sample and available results in informatics lab system was observed with the reduction time of centrifugation allowed by use of Barricor™ tube compared to regular heparin lithium tubes (p < 0.001). A significative decrease in hemolysis rate also occurred in the second period as samples with HI < 10 reached from 52.5% in the first period to 68.5% (p < 0.001) in the second. CONCLUSION: Low vacuum BarricorTM tubes allowing a higher speed of centrifugation improve lab TAT without impairment of sample quality as a significant reduction of hemolysis was observed, a double advantage which is of particular interest for ED.

Monthly reference change value of cardiac troponin in hemodialysis patients as a useful tool for long-term cardiovascular management.

PURPOSE OF RESEARCH: Circulating cardiac troponin (cTn) has been identified as a risk factor for cardiovascular and overall mortality in patients undergoing hemodialysis. However, its interpretation remains difficult due to the high prevalence of patients with cTn level beyond the 99th percentile. Determining the cTn reference change value (RCV) may help in assessing a clinically significant change of cTn during regular follow-up of patients. We aimed to determine the long-term RCV of cTn in such patients and to calculate the perdialytic reduction rate of cTn. DESIGN AND METHODS: To calculate RCV, high-sensitivity (hs)-cTnT (Roche), hs-cTnI (Abbott), and cTnI-ultra (Siemens) were determined every month before the midweek dialysis session over a 3-month period in 36 stable hemodialysis patients. cTn was also measured after the midweek dialysis session to calculate the cTn removal rate. RESULTS: The mean RCV (95% confidence interval) was 22% (18-26) for hs-cTnT versus 53% (34-73) for hs-cTnI versus 65% (45-84) for cTnI-ultra. Log-normal RCV (%) was -19/+25 for hs-cTnT, -33/+96 for hs-cTnI, and -39/+115 for cTnI-ultra. The index of individuality was <0.6 regardless of the cTn assay used. A significantly greater reduction rate was observed for hs-cTnT (48%) than for hs-cTnI (30%, p<0.001) and cTnI-ultra (29%, p<0.05). CONCLUSIONS: These results underline the need to use the RCV approach rather than cutoff points to identify the critical change in long-term serial cTn levels. In addition, RCV should be determined for each available assay due to significant differences between assays. Removal of cTn during hemodialysis sessions should also be considered if acute coronary syndrome is suspected during a session.

Association between breast milk fatty acids and HIV-1 transmission through breastfeeding.

A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and ß2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding.

Long term reference change value of creatinine in HIV-positive patients with anti-retroviral therapy: A new tool in clinical practice.

BACKGROUND: The use of reference change value (RCV) instead of reference interval emerged as an alternative approach for longitudinal interpretation of biological marker. Follow-up of creatinine variation in HIV-positive adults remains a challenge in order to prevent renal complications. OBJECTIVES: To determine the long term RCV of creatinine in HIV-positive adults receiving anti-retroviral therapy (ART) according to the use of tenofovir or ritonavir. DESIGN AND METHODS: Longitudinal study of 24 months that include 124 HIV-positive patients followed in HIV outpatient unit. Plasma creatinine was measured at 0, 6, 12 and 24 months in order to calculate the RCV. RESULTS: In the whole group, a 24-month RCV of creatinine was 22.5%. Whatever the ART, the index of individuality was <0.6. Significantly higher RCV of creatinine was observed in patients receiving the association tenofovir and ritonavir (28%) compared to the patients receiving i) tenofovir without ritonavir (21.9%), ii) no tenofovir but ritonavir (22.2%), and iii) no tenofovir and no ritonavir (19.7%). CONCLUSIONS: The low value of index of individuality pinpointed that RCV should be used to identify critical change in serial creatinine results in HIV-positive adults. RCV of creatinine under ART was around 20% but reached 28% in case of association of tenofovir and ritonavir.

Accuracy of GFR predictive equations in renal transplantation: validation of a new turbidimetric cystatin C assay on Architect c8000.

OBJECTIVES: To evaluate the Sentinel-PETIA cystatin C on Architect c8000 analyzer. DESIGN AND METHODS: We assessed analytical performances and clinical relevance by comparison with a reference isotopic method in kidney transplant recipients. RESULTS: This assay exhibited reliable precision and was close to the non standardized Siemens-PENIA method. All tested equations allowed reliable assessment of GFR. CONCLUSIONS: Cystatin C improved GFR determination at the critical level of 60 mL/min/1.73 m². New formulas might be necessary after IFCC standardization.

Evolution of coronary artery calcifications following kidney transplantation: relationship with osteoprotegerin levels.

We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV >or= 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395-5652] to 527 [217-1818] pg/mL and parathyroid hormone from 94 [1-550] to 62 [16-410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02-8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456-3285]) vs. non-progressors (899 [396-5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.

[Carbonyl stress and oxidatively modified proteins in chronic renal failure]. / Stress carbonylé et modifications oxydatives des protéines au cours de l'insuffisance rénale chronique.

Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis.

Association of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patients.

OBJECTIVES: To assess the relationship between non-classical cardiovascular (CV) risk factors including non-HDL cholesterol (non-HDL-C), apolipoprotein B, triglycerides to HDL ratio, LDL size, inflammation or oxidative stress parameters and carotid intima-media thickness (CIMT), in order to better identify prevention or therapeutic targets. In addition, we studied the relationship between metabolic syndrome (MS) and CIMT. METHODS: Cross-sectional study including 232 HIV-positive (HIV+) adults (80% treated by combined antiretroviral therapy) extracted from the ANRS CO3 Aquitaine Cohort. RESULTS: There was a significant association of higher non-HDL-C (p<0.01), apolipoprotein B (p<0.01) levels or TG/HDL ratio (p<0.05) with higher CIMT when compared the first vs fourth quartile, while there is no association between CIMT and LDL-C (p=0.09) or LDL size (p=0.55). In multivariate analysis, only the TG/HDL molar ratio > 1.5 tend toward significance (p=0.08). MS was observed in only 7.3% of patients with the NCEP-ATP III definition and 11.2% with the IDF criteria. Whatever the used definition, there was a significant association between MS presence and increased CIMT (p<0.05) in univariate and multivariate model. CONCLUSIONS: Non-HDL-C, TG/HDL ratio and apolipoprotein B levels, which are closely linked to lipid disorders associated to the MS, appear as stronger predictive markers than LDL-C for screening subclinical atherosclerosis in HIV+ populations. Achieving non-HDL-C target defined by the NCEP-ATP III guidelines appears of great importance to reduce CV complications in HIV+ patients.

Adaptation and evaluation of the Randox full-range CRP assay on the Olympus AU2700.

The implementation of a high-sensitivity CRP (hs-CRP) assay as a routine laboratory parameter may be necessary. A single CRP method that could yield reliable results for the whole concentration range (0.1-200 mg/L) would be the most practical solution for the laboratory setting. The aim of this study was to assess the Randox full-range CRP assay on the Olympus AU2700 biochemistry analyzer and evaluate its analytical performance on serum and heparin plasma samples. The Randox CRP turbidimetric assay was compared with the existing CRP assay used routinely on the Olympus AU2700. The analytical performance of the Randox CRP with both Olympus CRP reagents (CRP for normal application and hs-CRP) was good. We found that the Randox CRP method in the range of 0.5-160 mg/L was closely correlated to the Olympus CRP and hs-CRP for serum samples. According to a Bland-Altman analysis, the serum and heparinized samples showed an excellent agreement in CRP concentrations throughout the entire range (mean difference = -0.035 +/- 1.806 mg/L) as well as in CRP levels <10 mg/L. Our data indicate that Randox full-range CRP measurements using an immunoturbidimetry assay on Olympus systems perform as well for routine diagnostics as other high-sensitivity applications using serum or heparin plasma.

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism. RESULTS: The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.

High prevalence of small dense LDL as an underestimated component of heart transplantation-induced dyslipidemia: potential role in graft coronary vasculopathy?

Heart transplantation-induced dyslipidemia is a recognized risk factor for cardiac allograft vasculopathy that affects survival prognosis. Beyond increased lipids, low-density lipoprotein (LDL) size and systemic factors, including glucose intolerance, oxidative stress, and inflammation, must be taken into account as components of the atherosclerotic risk. The aim of this study was to explore the atherogenic profile of heart transplant recipients (HTR) by assessing lipid parameters, glycemia, oxidative stress status, and inflammation in 59 transplant patients (follow-up of 6 +/- 3 years) compared to 20 healthy volunteers. Classical hypercholesterolemia and hypertriglyceridemia were observed in HTR compared to controls, associated with increased apoCIII levels (0.13 +/- 0.6 vs 0.07 +/- 0.03 g/L, P < .01). Mean LDL size was reduced in HTR compared to controls (25.22 +/- 0.72 vs 26.06 +/- 0.54 nm, P < .001) with an abnormally high prevalence (69% vs 0%, P < .001) of small dense LDL (<25.5 nm). Hyperglycemia (7.3 +/- 3 vs 5.4 +/- 0.8 mmol/L, P < .05) and inflammation (high-sensitive CRP: 3.1 +/- 3 vs 1.6 +/- 0.9 mg/L, P < .001) were evidenced in HTR since no difference in oxidative stress parameters was observed. In conclusion, a high prevalence of small dense LDL is an important component of posttransplantation dyslipidemia.

Comparison between the enzymatic vitros assay for creatinine determination and three other methods adapted on the Olympus analyzer.

To evaluate the relationship between the enzymatic Vitros assay for creatinine determination and other methods, we determined creatinine concentration in 400 heparin samples. Plasma creatinine level was successively determined on the Vitros 750 analyzer (Johnson & Johnson Co., Rochester, NY) and on the Olympus AU2700 analyzer (Olympus France, Rungis, France), using three reagents in the same assay: Olympus-Jaffé and two enzymatic commercial kits-Crea Plus (Roche Diagnostics, Meylan, France) and Enzymatic Creatinine (Randox, Mauguio, France). Comparison of Jaffé and enzymatic measurements of plasma creatinine levels revealed a high correlation when considering all values ranged from 20-1000 micromol/l (r > 0.99). However, for values <60 micromol/l, enzymatic reagents provided best results. Enzymatic methodology is a better clinical choice for the accurate measurement of creatinine, especially for neonates, pediatrics, and hematology units. Because analytical performance and the costs of Randox creatinine were satisfactory for our laboratory, this method, adapted on the Olympus analyzer, was chosen for routine determination of creatinine levels. According to the Valtec protocol (8), no interferences such as hemolysis, lipemia, or bilirubin were detected for Enzymatic Creatinine Randox.

Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed during highly active antiretroviral therapy (HAART) including protease inhibitor. Apolipoprotein (apo) CIII could be involved in this HTG by inhibition of triglyceride (TG) hydrolysis, which leads to the occurrence of small dense low density lipoprotein (sdLDL), a recognized cardiovascular risk factor. OBJECTIVE: To characterize the influence of lopinavir/ritonavir-containing regimen on lipoprotein profile. DESIGN AND METHODS: 24 antiretroviral-experienced HIV infected adults (including 14 patients in therapeutic interruption of at least 2 months) and 14 HIV uninfected healthy controls were enrolled. Serum lipid parameters (total cholesterol (TC), HDL-C, LDL-C, TG, apoA1, apoB, apoCIII), lipoprotein composition and LDL size were determined before initiation of lopinavir/ritonavir-containing regimen, and at 1 and 3 months thereafter. RESULTS: At baseline an atherogenic lipid profile was evidenced, characterized by a moderate HTG associated to a smaller mean LDL size (25.16 vs 25.93 nm, P<0.001), an enrichment in TG of LDL (11.4 vs 6.0%, P<0.01) and a high prevalence of sdLDL (75 vs 7%, P<0.01) when compared to controls. After 1 month of lopinavir/ritonavir-containing regimen, a significant reduction of LDL size (24.81 vs 25.16 nm, P<0.05) and a significant increase in cholesterol total (5.53 vs 4.49 mmol/l, P<0.001), in TG (4.20 vs 2.01 mmol/l, P<0.001), in apoA1 (1.28 vs 1.11 g/l, P<0.001), in apoB (1.08 vs 0.94 g/l, P<0.01), in apoCIII (0.16 vs 0.10 g/l, P<0.001), in TG percentage in LDL (14.4 vs 11.4, P<0.05) and in TG percentage in HDL (10.2 vs 8.3, P<0.05) were observed. CONCLUSIONS: Advanced stage of HIV infection is associated with an atherogenic lipid profile including a high prevalence of sdLDL. Lopinavir/ritonavir-containing regimen accentuates the reduction of LDL size. Since fibrates decrease TG and increase LDL size, they appear as a logical option to manage HAART-induced HTG.

Discrepancies between apolipoprotein E phenotyping and genotyping in the elderly.

We estimated the frequencies of phenotype (isoelectric focusing; IEF) vs. genotype (PCR/Hhal) discordance in a sample of an aged population (> 65 years). Both phenotype and genotype techniques have been used in the study of apolipoprotein E (apoE) polymorphism in 125 elderly subjects. The discordance between phenotype and genotype was unresolved in 11 (8.8%) of the 125 unrelated subjects studied. We observed a significant association between the presence of the E4 allele and both Alzheimer's disease (chi2 = 13, p < 0.001) and increased cholesterol concentration (Mann Whitney, p < 0.03). These relationships were not affected by the techniques used. Our results indicate that transcriptional modulation and post-transductional modifications in normal ageing and in aged-related diseases may explain in part discrepancies between gene analysis and protein characterisation.

The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer's disease.

BACKGROUND: Human apolipoprotein (Apo) E4 (ApoE4) is an important determinant of lipid metabolism and cell-to-cell cholesterol transport. It is also a major genetic risk factor for both vascular disease and familial and sporadic late-onset Alzheimer's disease (AD). Since vascular pathology could dramatically reduce neuronal reserve capacity, a biological chain of events between ApoE4, hypercholesterolemia and AD has been postulated. The aim of the present study is to explore the relationship between lipid metabolism and ApoE isoforms in a large series of elderly subjects in relation to the presence or absence of AD. METHODS: Of 332 referrals to a neurology clinic specializing in memory disorders, 146 were given a diagnosis of AD (age, mean +/- SD 76 +/- 13.1 years, 64.4% women) according to DSM-IIIR criteria. One hundred and seventy-six subjects were included as controls (age 80 +/- 5.6 years, 58% women). The ApoE phenotype was determined by the isoelectrofocalization method, cholesterol, triglycerides, phospholipids, ApoA and ApoB were determined by routine chemistry. FINDINGS: A significant association was observed between the E4 allele and AD (chi2 = 13, p < 0.001) only below age 80. In the control group, cholesterol levels were found to be significantly higher in men but not in women with an E4 allele (6.35 +/- 1.3 mmol/l) as opposed to those without (5.8 +/- 1.2 mmol/l). ApoB levels were also found to be higher in the presence of ApoE4, with no gender effect. Within the AD group no significant relationship was found between ApoE4 and cholesterol levels (mean 6.05 +/- 0.9 mmol/l in E4-AD subjects versus 5.8 +/- 1.21 mmol/l in non-E4-AD subjects). Similar observations were made in relation to triglycerides and phospholipids. INTERPRETATION: Our results demonstrate the disappearance of the ApoE4-raising effect on serum cholesterol, triglyceride and phospholipid levels in AD suggesting a more complex relationship between AD and lipid metabolism than has previously been supposed. This lipid abnormality may further contribute to the progression of AD.

Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation.

Oxidative stress can produce profound alterations to cellular membrane lipids, impairing cell metabolism and viability. This phenomenon, previously observed in haemodialysis patients, has been proposed as a significant factor in regard to haemodialysis-related shortened red blood cells (RBC) survival. In the present study, several parameters associated with oxidative stress were evaluated in a group of haemodialysis patients either receiving erythropoietin therapy (n = 12, mean erythropoietin dose 88 +/- 24 U/kg/week) or not receiving such therapy (n = 30), and in 38 controls. Malonyldialdehyde (MDA, nmol/ml), an end-product of lipid peroxidation, and RBC antioxidant systems were measured, including RBC alpha-tocopherol (RBC vitamin E, mg/l), RBC glutathione (GSH, nmol/mgHb), and RBC superoxide dismutase activity (SOD, U/mgHb). Plasma vitamin E concentrations were also evaluated. Finally, oral vitamin E supplementation (500 mg daily), an exogenous antioxidant, was administered for 6 months to seven patients from the dialysis group receiving erythropoietin while oxidative parameters were repeatedly evaluated and erythropoietin requirements monitored, in order to appreciate the therapeutic relevance of an antioxidant supplementation. An elevation of serum MDA was observed in all haemodialysis patients and a significant decrease in RBC vitamin E, despite normal serum vitamin E levels. Furthermore, the reduction in RBC vitamin E was more important in patients treated with erythropoietin. Vitamin E supplementation resulted in a significant increase in RBC vitamin E (from 0.3 +/- 0.1 to 1.2 +/- 0.2 mg/l of pellet) and a reduction in erythropoietin dose (from 93 +/- 24 to 74 +/- 26 U/kg/week) while maintaining stable haemoglobin concentrations. These results suggest that the oxidative stress could be one of the resistance factors to erythropoietin response in haemodialysis and that vitamin E supplementation could have a sparing effect on erythropoietin dosage requirement.

[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?]. / Stress oxydant et insuffisance rénale chronique: quelles peuvent être les approches prophylactiques?

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.