Oxidative Stress In Hemodialysis Patients Research Articles

Dietary acid load and markers of malnutrition, inflammation, and oxidative stress in hemodialysis patients.

The present study was conducted to examine the association between dietary acid load (DAL) and markers of inflammation, oxidative stress, and malnutrition in a group of Iranian hemodialysis (HD) patients. This cross-sectional study was performed on individuals aged ≥18 years who were on HD at least 6 months before their enrollment in the study. A 4-day dietary recall was used for the evaluation of dietary intake. DAL was calculated using two methods including potential renal acid load (PRAL) and net endogenous acid production (NEAP). For assessing the malnutrition status, we used the subjective global assessment (SGA), dialysis malnutrition score (DMS), and malnutrition inflammation score (MIS). Fasting blood samples were collected from each participant to assess serum levels of high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), and endothelin-1. In total, 291 patients with a mean age of 57.73 ± 0.88 years and HD vintage of 4.27 ± 0.25 months were enrolled in the current study. Significant positive associations were observed between PRAL and hs-CRP (β = 1.77, 95% CI: 0.88, 2.65), sICAM-1 (β = 83.21, 95% CI: 10.39, 156.04), sVCAM-1 (β = 194.63, 95% CI: 74.68, 314.58), and sE-selectin (β = 6.66, 95% CI: 1.81, 11.50) among participants with the highest PRAL scores, compared to those with the lowest PRAL scores. NEAP was positively correlated with hs-CRP (β = 1.34, 95% CI: 0.46, 2.22), sICAM-1 (β = 88.83, 95% CI: 16.99, 160.67), and MDA (β = 0.35, 95% CI: 0.005, 0.71). Additionally, marginally significant higher odds of SGA (OR = 1.98, 95% CI: 0.95, 4.11) and DMS (OR = 1.94, 95% CI: 0.92, 4.05) were observed in individuals in the third tertile of PRAL vs. the first tertile of PRAL. NEAP had also a marginally significant positive correlation with DMS (OR = 2.01, 95% CI: 0.93, 4.31). This study illustrates that higher consumption of acidic foods is correlated with markers of inflammation, oxidative stress, and malnutrition in HD patients.

253 Post-COVID Syndrome-Associated Oxidative Stress in Hemodialysis Patients

253 Post-COVID Syndrome-Associated Oxidative Stress in Hemodialysis Patients

Long-COVID sequelae are associated with oxidative stress in hemodialysis patients

pathophysiology of long-COVID sequelae in the general population of SARS-CoV-2-infected patients has been shown to be strongly influenced by oxidative stress. However, the potential role of oxidative stress in the development of long-COVID sequelae in hemodialysis patients (HD) has never been investigated.
 The present study aimed to evaluate the oxidative status of HD patients 3.5 months after SARS-CoV-2 infection in relation to the presence of long-COVID sequelae and the severity of the acute phase COVID-19.
 Methods. This cross-sectional cohort study included 63 HD patients with a median age of 55 (43-62.5) years and a dialysis vintage of 42 (25-73) months who had been infected with COVID-19 at least 3 months before recruitment. Patients were divided into two groups according to the occurrence of long-COVID sequelae: Group 1 included 31 (49.2%) HD patients with sequelae, while Group 2 included 32 (50.8%) fully recovered individuals. At 3.5 (3.2-4.6) months after the acute phase of COVID-19, malondialdehyde (MDA) and erythrocyte levels (MDAe), sulfhydryl groups (SH -groups), serum catalase activity, transferrin, and ceruloplasmin were measured. A comparison of the obtained data was performed using the Student’s test or the Mann-Whitney test according to the data distribution. A correlation was evaluated with the Spearman test.
 Results. HD patients with persistent long-COVID sequelae had significantly higher concentrations of MDAs (p = 0.002), MDAe (p = 0.0006), and CTs (p = 0.02), and lower serum levels of SH-groups (p = 0.03) and ceruloplasmin (p = 0.03) compared with Group 2. The concentration of most studied indicators of pro- and antioxidant status did not depend on the severity of the acute phase COVID-19, and only catalase activity was statistically significantly related to the need for hospitalization (r = 0.59; p = 0.001), oxygen support (r = 0.44; p = 0.02), and the percentage of lung injury according to computed tomography (p = 0.03). Although the serum concentration of transferrin did not differ between the studied groups, the individual analysis showed that its value was statistically higher in HD patients with severe COVID-19 even 3.5 months after infection (p < 0.0001).
 Conclusions. Long-term COVID-19 sequelae in HD patients are associated with oxidative stress. High levels of catalase activity and serum transferrin 3.5 months after COVID-19 may be a consequence of the severe course of the acute phase of the disease. The obtained data suggest that the use of antioxidants may be one of the possible strategies to treat the long-term consequences of COVID in HD patients.

Oxidative stress in hemodialysis patients infected with HIV

Background: HIV-infected population presents the impaired renal function as a risk factor for death, and comorbid conditions are related in some traits to oxidative stress (OS). Objetive: To analyze the influence of OS in Human Immunodeficiency Virus Infection (HIV) and chronic kidney disease (CKD) by comparing the redox status between HIV patients with and without CKD and HIV hemodialysis patients. Methods: A comparative longitudinal study of the hemodialysis process was developed. The study included 96 individuals divided into four groups namely, supposedly healthy volunteers, patients with HIV infection without renal illnesses, patients with HIV infection and chronic renal disease, and HIV(-) with chronic renal disease. Indexes evaluating redox, hematological, hemochemical, immunologic, and virological aspects were determined. These indexes were also assessed before and after hemodialysis. Results: Viral load, uric acid, creatinine, and urea concentration were significantly (p<0.05) lower after hemodialysis. The two HIV infected groups were significantly different (p<0.05) regarding redox indexes of damage and antioxidant status compared to the group of supposedly healthy volunteers. Significantly increased values (p<0.05) of malondialdehyde, advanced oxidation protein product (AOPP), and peroxidation potential (PP) and significantly lower values glutathione (GSH) (p<0.05) were found after hemodialysis in both groups. In the case of HIV patients, increased values of superoxide dismutase were also found. HIV infected patients under HD tretament exhibited significantly (p<0.05) higher values of AOPP and PP and lower values of GSH than HIV(-) hemodialysis patients after hemodialysis. Conclusion: Oxidative stress occurs in both HIV and CKD conditions, and it is also increased after hemodialysis intervention. Otherwise non-viral control could influence on oxidative status in HIV/CKD patients, that´s why ART affectivities should be monitoring using HIV progression markers. Redox indexes should be diagnosed in HIV hemodialysis patients for treatment and management adjustment.

MO929: Oxidative Stress in Hemodialysis Patients

Abstract BACKGROUND AND AIMS It is known that chronic kidney disease (CKD) is associated with complications such as anaemia, mineral bone disorders (CKD-MBD) or diselectrolytemia.Therefore, the diet of renal patients is restricted in different nutrients such as potassium or phosphorus, a fact that could potentially increase oxidative stress [1]. We investigated the relationship between an oxidative damage marker (malondialdehyde-MDA) on the one hand, and plasma antioxidant status (glutathione peroxidase-GPx) activity on the other hand with the nutritional status and with complications associated with CKD (anaemia, CKD-MBD). METHOD We conducted a single-centre cross-sectional study that included 58 CKD G5D patients (mean age of 60.39 ± 11.73 years; 33 males, 25 females; mean haemodialysis vintage of 6.43 ± 4.89 years). All patients have been assessed regarding dialysis status (medical history). We performed analysis before the dialysis session using standard methods blood biochemistry, complete blood count and using spectrophotometry (HPLC)-malondialdehyde and glutathione peroxidase. RESULTS The studied patients’ mean malondialdehyde was 1.41 ± 0.42 mcmol/L, while mean glutathione peroxidase was 58.65 ± 12.15 U/g Hg. The oxidative stress markers did not show any statistically significant correlation with age, gender, dialysis vintage or with predialysis urea and bicarbonate. Patients with a BMI > 30 kg/sqm (21 versus 37 patients) showed a significantly higher level of MDA 1.57 ± 0.51 mcmol/L versus 1.31 ± 0.33 mcmol/L, P = 0.02. We have also found a negative statistically significant correlation between MDA level and serum K (r = –0.29, P = 0.02) and serum phosphorus (r = –0.29, P = 0.03). Patients with predialysis K of higher then 5.5 mEq/L had a statistically significant lower MDA (1.29 ± 0.4 mcmol/L versus 1.54 ± 0.4 mcmol/L, P = 0.025) and a non-significant higher GPx (59.0 ± 12.58 U/g Hg versus 58.2 ± 11.87 U/g Hg, P = 0.8). We found a negative statistically significant correlation of the MDA level with haemoglobin (r = –0.39, P = 0.002) and with haematocrit (r = –0.35, P = 0.006). No statistically significant correlation of the plasma antioxidant GPx with the studied parameters of anaemia and CKD-MBD has been found. CONCLUSION In our study, we found that increased oxidative stress (expressed through the malondialdehyde level) is associated with obesity and more severe anaemia. The indirect relationship found with serum K and phosphorus could indicate the risk of oxidative stress, and therefore it could be useful to take into account the dietary antioxidants when recommending low potassium and low phosphorus diet.

Effects of Probiotics, Prebiotics, and Synbiotics on Uremic Toxins, Inflammation, and Oxidative Stress in Hemodialysis Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The dysbiosis of gut microbiota may cause many complications in patients with end-stage renal disease, which may be alleviated by probiotic, prebiotic, and synbiotic supplementation. The aim of this systematic review and meta-analysis was to assess the effects of these supplementations on circulatory uremic toxins, biomarkers of inflammation, and oxidative stress in hemodialysis patients. We searched the EMBASE, MEDLINE, Web of Science, and Cochrane Library databases until 8 August 2021. Randomized controlled trials evaluating adult patients receiving hemodialysis were included. The pooled results from 23 studies with 931 hemodialysis patients indicated that interventions significantly decreased the circulating levels of p-cresyl sulfate (standardized mean difference (SMD): 0.38; 95% CI: −0.61, −0.15; p = 0.001), endotoxins (SMD: −0.58; 95% CI: −0.99, −0.18; p = 0.005), malondialdehyde (SMD: −1.16; 95% CI: −1.81, −0.52; p = 0.0004), C-reactive proteins (CRP) (SMD: −0.61; 95% CI: −0.99, −0.23; p = 0.002), and interleukin 6 (SMD: −0.92; 95% CI: −1.51, −0.33; p = 0.002), and improved the total antioxidant capacity (SMD: 0.89; 95% CI: 0.49, 1.30; p < 0.0001) and glutathione (SMD: 0.40; 95% CI: 0.14, 0.66; p = 0.003) when compared to the placebo group. Our results suggest that treatment with probiotics, prebiotics, and synbiotics may help alleviate uremic toxin levels, oxidative stress, and the inflammatory status in hemodialysis patients.

The effects of vitamin E supplementation on malondialdehyde as a biomarker of oxidative stress in haemodialysis patients: a systematic review and meta-analysis

BackgroundHaemodialysis (HD) patients tend to have higher levels of oxidative stress (OS), associated with increased morbidity and premature mortality, compared to the general population. Levels of malondialdehyde (MDA), a biomarker of OS, are reduced by the antioxidant properties of vitamin E (VE) but outcomes from randomised control trials of VE supplementation on MDA in HD patients have been inconsistent.MethodsWe undertook a systematic review and meta-analysis of adult HD patients from VE supplementation studies with measures of MDA. The following search criteria of MEDLINE and EMBASE were considered from inception to January 2020: ‘dialysis’ AND ‘Vitamin E OR tocopherol’ AND ‘malondialdehyde OR MDA’. Two reviewers independently extracted study data and assessed risk of bias. Mean MDA levels and standard deviation were determined before and after VE supplementation. Standardised mean difference (SMD) and standard error were calculated as the within person difference and units of measure were not consistently recorded across all studies. The SMD were pooled using random effects meta-analysis.ResultsThe SMD of MDA levels from 18 comparisons was significantly lower in HD patients following VE supplementation (− 1.55; confidence interval: − 2.17 to − 0.94, P < 0.00001). There were significant levels of heterogeneity between studies (I2 value = 91%; P < 0.00001) with evidence of potential publication bias toward smaller studies.ConclusionsOur findings support the use of VE to reduce the effects of OS in HD patients although high levels of heterogeneity and variation in the methodological approaches used by some studies highlight the need for further investigation.

Vitamin E-Bonded Membranes Do Not Influence Markers of Oxidative Stress in Hemodialysis Patients with Homozygous Glutathione Transferase M1 Gene Deletion.

Background: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. Methods: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. Results: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. Conclusions: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis.

Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p=0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p=0.005 and p=0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p=0.6; p=0.4 and p=0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

Evaluation of the Relationship Between Advanced Oxidation end Products and Inflammatory Markers in Maintenance Hemodialysis Patients

Introduction Increased oxidative stress and blunted anti-oxidant mechanisms are important problems in hemodialysis (HD) patients. Reactive oxygen species (ROS) act directly on proteins, leading to the formation of oxidized amino acids. Advanced oxidation protein products (AOPP) are among these substances. Many oxidant substances increase the level of AOPP. Iron is an element with strong oxidant capacity, especially when used intravenously. It is thought that iron treatment further increases the oxidative stress in HD patients. We aimed to investigate the relationship between AOPP and inflammatory status in HD patients. Materials and Methods Patients who were on maintenance HD program without additional co-morbidities and no history of use of intravenous iron within the last two weeks were recruited in the study. The blood samples taken just before the dialysis session were analyzed for AOPP, serum iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), ß2-microglobulin, fibrinogen, interleukin (IL)-1, IL-6 and tumor necrosis factor-α levels besides routine biochemical measurements and complete blood count. Results The number of patients included in the study was 102 (n: 53 female, %52.0) and the mean age was 47.6±13.9 years. The mean transferrin saturation was 25.4%. AOPP levels, iron use in patients was higher compared to patients who do not use (respectively 2.58±0.19 mmol/l and 2.50 ±0.16mmol/l, p = 0.046). We did not detect statistically significant correlation of AOPP levels with iron parameters and other inflammatory markers. Conclusion The present study showed that intravenous iron therapy does not increase oxidative stress. Although serum AOPP level was higher in patients on intravenous iron treatment, it was not correlated with iron indices and inflammatory markers. So, intravenous iron may exert its oxidant effect free from serum iron indices.

Oxidative Stress in Hemodialysis Patients: Pathophysiological Mechanisms, Clinical Consequences and Basic Principles of Treatment

Abstract Cardiovascular diseases are the leading cause of death in patients who undergo regular hemodialysis. Oxidative stress is a non-traditional risk factor for the development of cardiovascular diseases in this population of patients. It is defined as tissue damage caused by balance disturbance between the formation of free radicals and the function of protective antioxidative systems. The superoxide anion and hydrogen peroxide are precursors in the formation of stronger oxidants, such as: hydroxyl radical, peroxynitrite and hypochloric acid. Superoxide dismutase is the first line of antioxidant protection while catalase, glutathione peroxidase, trace elements, vitamin C, vitamin E, N-acetylcysteine and coenzyme Q10 also have a significant antioxidative role. Hemo-dialysis is itself a trigger for the increased formation of oxygen free radicals. The two main pathophysiological mechanisms of the increased formation of free oxygen radicals during the hemo-dialysis session are: bionicompatibility of the dialysis membrane and the presence of endotoxins in the hemodialysis solution. The measurement of myeloperoxidase concentration in a patient’s serum during hemodialysis is an indicator of the severity of oxidative stress induced by the dialysis membrane (an indicator of the biocompatibility of the dialysis membrane). The main clinical consequences of oxidative stress include: atherosclerosis, erythropoietin resistance, malnutrition and amyloidosis associated with hemodialysis. The evaluation of oxidative stress in patients undergoing hemodialysis is performed by measuring the concentration of lipid peroxidation products (malonyldialdehyde, 4-hydroxynonenal, TBARS, F2-isoprostane, oxLDL), protein oxidation (AOPP), protein gelling (AGE), and oxidation of nucleic acids (8-OHdG). The antioxidant treatment strategy consists of replenishing vitamin C, vitamin E, selenium, N-acetylcysteine and coenzyme Q10. On-line hemodialysis, a biocompatible vitamin E-coated dialysis membrane, an ultra-pure solution for hemodialysis, prevent oxidative stress, reduce the rate of cardiovascular morbidity and mortality and improve life quality of patients treated with regular hemodialysis.

Effect of febuxostat on oxidative stress in hemodialysis patients with endothelial dysfunction: a randomized, placebo-controlled, double-blinded study.

Oxidative stress, which is most likely a key mediator in the development of cardiovascular disease, is implicated in the progression and deterioration of chronic kidney disease. Patients on hemodialysis exhibit the excessive generation of oxidative stressors, which may also be responsible for the endothelial dysfunction prevalent in these patients. Febuxostat, an inhibitor of xanthine oxidase enzyme, is emerging as a novel drug in the amelioration of oxidative stress status. However, studies regarding its effect among hemodialysis patients are still lacking. This prospective, block-randomized, double-blinded, placebo-controlled study was carried out to assess the effect of oral 40mg febuxostat on oxidative stress in hemodialysis patients. In total, fifty-seven eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. Serum malondialdehyde (MDA) and serum superoxide dismutase (SOD) were assessed at baseline and at the end of the study. A correlation analysis between previously reported serum asymmetric dimethylarginine (ADMA), serum MDA and serum SOD was performed. Febuxostat significantly decreased the serum MDA and significantly increased the serum SOD, while no significant results were observed in the placebo group. A highly positive correlation between the MDA levels and ADMA levels at baseline was noticed in both groups, while there was a highly negative correlation between the SOD levels and ADMA levels at baseline in both groups. A positive correlation between the change in ADMA levels and MDA levels from baseline was observed only in the drug group. Febuxostat appears to have a direct ameliorating effect on oxidative stress in hemodialysis patients with endothelial dysfunction.

Lycopene supplementation decreases oxidative stress in hemodialysis patients receiving intravenous iron therapy: An open-label, randomized controlled clinical trial

The aim of our study was to evaluate the effect of lycopene on the antioxidant status and the level of homocysteine (HCY) in dialysis patients receiving intravenous iron therapy. A total of 60 hemodialysis patients receiving intravenous iron therapy were randomly assigned to the treatment group and the control group. Patients in the treatment group (n = 30) received oral lycopene and intravenous iron, while patients in the control group (n = 30) only received intravenous iron therapy. At the initiation of the study, oxidant indexes and HCY concentration were tested. After 8 weeks, all of the laboratory variables were repeatedly evaluated. At the initiation of the study, no significant differences were found in the level of oxidant stress and the level of HCY between two groups. After 8 weeks, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) decreased, while the levels of malondialdehyde (MDA) and homocystinuria (HCY) increased in both the groups. Besides, the levels of SOD and GSH-px were higher and the level of MDA was lower in the treatment group than in the control group ( P &lt; 0.05, respectively). The level of HCY in the treatment group was relatively low, but there was no significant difference between the two groups. In conclusion, we found that 8-week lycopene supplementation attenuated oxidative stress in hemodialysis patients receiving intravenous iron therapy.

Effects of HBV and HCV infection on oxidative stress and inflammation in hemodialysis patients

Background and purpose: Chronic renal failure is a syndrome characterized by progressive and irreversible loss of nephrons depending on various diseases. Especially infection such as HBV and HCV is among the major causes of mortality and morbidity in hemodialysis patients. In the present study we aimed to determine the levels of 3-nitrotyrosine (3-NT), TNF-like weak inducer of apoptosis (TWEAK) and heat shock protein (HSP70) in chronic renal failure patients diagnosed with HBV, HCV and non-hepatitis undergoing hemodialysis treatment. Materials and methods: Samples of 235-patients receiving hemodialysis treatment and 25-healthy individuals were included in the study. Firstly, HBV and HCV positivity were diagnosed by serological Enzyme-Linked ImmunuSorbent Assay (ELISA) method. Then, 3-NT levels were determined using High-Performance Liquid Chromatography (HPLC), while TWEAK and HSP70 were determined using high sensitivity ELISA. The numbers of patients used in the studies were determined according to statistical power analysis.Results: The values of 3-NT and HSP70 were found to be significantly higher non-hepatitis patients, HBV and HCV patients receiving hemodialysis treatment to compared with the control group (p‹0.05). Concentration of TWEAK in non-hepatitis and HBV patients receiving hemodialysis therapy was found to be significantly higher to compared with the control group (p‹0.05). However, unlike the other two groups, an increase in the TWEAK of HCV patients on post-dialysis was determined.Conclusions: To prevent the increase of inflammation and oxidative stress in hemodialysis patients or to keep it under control, investigating certain parameters such as TWEAK, 3-NT and HSP70 from time to time is of great importance in terms of minimizing the level of risk for many diseases such as cardiovascular diseases. Infection also increases the burden on oxidative stress and immunity system in these patients.

Treatment Based on Cinacalcet Reduces Oxidative Stress in Hemodialysis Patients with Secondary Hyperparathyroidism

Background/Aims: Oxidative stress is one of the leading factors contributing to increased mortality in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly used in the treatment of sHPT in patients with CKD. The aim of this study was to assess the influence of treatment with cinacalcet on the oxidative stress markers in patients on hemodialysis with sHPT. Methods: In 58 hemodialysed patients with sHPT (parathyroid hormone [PTH] > 300 pg/mL) plasma Advanced Oxidation Protein Products (AOPP), serum total antioxidant capacity – ImAnOx (TAS/TAC), serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 6 months of treatment. Results: Serum PTH concentration decreased significantly from 895 (748–1,070) to 384 (289–510) pg/mL after 6 months of treatment; p < 0.0001. Mean serum concentrations of ­calcium and phosphate remained stable. Plasma AOPP concentration decreased significantly from 152 (126–185) to 49 ­(43–57) µmol/L after 6 months of treatment; p < 0.0001. ImAnOx significantly increased from 260 (251–270) to 272 (264–280) µmol/L; p = 0.04. After 6 months of treatment, a significant, positive correlation was found between ImAnOx and the daily dose of cinacalcet (r = 0.30; p = 0.02). Also, the change of serum ImAnOx during treatment with cinacalcet significantly correlated with the daily dose of cinacalcet r = 0.35; p = 0.01. No significant correlations were found between plasma AOPP concentration or ImAnOx and PTH, or their changes in time. Conclusions: (1) Six-month treatment based on cinacalcet seems to reduce oxidative stress markers in maintenance hemodialysis patients with sHPT. (2) This benefit may be related rather to the direct action of cinacalcet than to the serum PTH concentration decrease.

P-343 - An adaptive response to oxidative stress in patients with chronic renal failure who were diagnosed with hepatitis B and C; Hsp70

Immune disorders are observed in chronic renal failure (CRF) patients for many reasons. The immunity to these patients is further increased by the addition of viral agents. HBV and HCV are common infectious agents in kidney patients and effect of oxidative stress. Hsp70 is an extracellularly expressed molecule, although it is essentially an intracellular protein that increases expression in the organism under stress. HSP70 induction is thought to be an adaptive response to increased oxidative stress. In this study, it was aimed to determine Hsp70 in CRF patients diagnosed with HBV and HCV. Samples of 235-patients receiving hemodialysis treatment and 25-healthy individuals were included in the study. Hsp70 was determined using high sensitivity ELISA. The Hsp-70 was found to be higher in non-hepatitis, HBV and HCV patients receiving hemodialysis therapy than those of control. When pre and post dialysis are compared, a minimal increase in post dialysis among HBV, HCV and non-hepatitis groups was observed (p›0.05). To prevent the increase of inflammation and oxidative stress in hemodialysis patients or to keep it under control, investigating certain parameters such as Hsp70 from time to time is of great importance in terms of minimizing the level of risk for many diseases.

Effect of high amylose resistant starch (HAM-RS2) supplementation on biomarkers of inflammation and oxidative stress in hemodialysis patients: a randomized clinical trial.

Systemic inflammation and oxidative stress play a central role in the pathogenesis of cardiovascular disease and numerous other complications of CKD. Recent studies demonstrated that consumption of a diet enriched with amylose (HAM-RS2), attenuates oxidative stress and inflammation, and improves intestinal microbiome in CKD rats. The present study was designed to explore the effect of dietary amylose supplementation in hemodialysis patients. Forty-six stable hemodialysis patients were randomized to receive biscuits containing 20 g/day during the first four weeks and 25 g/day in the next four weeks of either HAM-RS2 or wheat-flour. Fasting predialysis blood samples obtained before, during and at the end of trial were processed for biomarkers of oxidative stress and inflammation. There was no significant difference in baseline clinical or biochemical parameters between the two groups. Serum levels of TNF-α, IL-6, and malondialdehyde declined significantly (P < 0.05) in the HAM-RS2-treated group but remained unchanged in the placebo-treated group. No significant difference was observed in serum Interleukin-1β (IL-1β) and hs-CRP concentrations and total antioxidant activity between two groups. Serum urea and creatinine concentrations significantly declined and severity of constipation improved in HAM-RS2-treated patients (P < 0.05). HAM-RS2 consumption was well tolerated and did not cause discernible side effects. Administration of HAM-RS2 for eight weeks significantly reduced levels of inflammatory and oxidative markers in hemodialysis patients confirming the results observed in CKD animals. Long term trials are needed to explore the impact of HAM-RS2 supplementation on clinical outcomes in end stage renal disease population.

Elevated Neutrophil Gelatinase Lipocalin Levels Are Associated With Increased Oxidative Stress in Hemodialysis Patients.

BackgroundAdministration of intravenous iron is an essential treatment of anemia in hemodialysis patients, but it may lead to oxidative stress and increased morbidity and mortality. There is evidence that neutrophil gelatinase-associated lipocalin (NGAL) is protective against oxidative stress and thus the aim of the present study was to investigate the relationship between plasma NGAL and advanced oxidative protein products (AOPP) in hemodialysis patients treated with intravenous iron.MethodsIn a prospective study, 47 hemodialysis patients (mean age 63 years, SD = 13.6; 40% women) were enrolled from two separate hospitals. Oxidative stress was induced by an intravenous administration of 100 mg iron saccharate 0.5 h after the start of dialysis. Blood samples were drawn at the beginning of the dialysis, 0.5 h after iron administration and at the end of dialysis. NGAL levels were measured from the first blood sample, AOPP levels were measured from all blood samples.ResultsOur results showed that higher NGAL and AOPP levels at the beginning of the dialysis, prior to iron administration, significantly predicted higher levels of AOPP toward the end of dialysis, (β = 0.355, SE = 0.054, P = 0.035; β = 0.297, SE = 0.159, P = 0.043, respectively).ConclusionsOur results suggest that higher level of NGAL is a risk factor for oxidative stress, as measured by AOPP levels, in dialysis patients receiving intravenous iron. Our findings could identify dialysis patients who are at higher risk from iron supplementation via measurement of NGAL levels.

Sleep apnea syndrome, inflammation and oxidative stress in hemodialysis patients.

Sleep apnea syndrome (SAS) is an established cardiovascular risk factor in the general population related to inflammation and oxidative stress and is very common among hemodialysis patients. Cardiovascular disease and its complications is the main cause of death among hemodialysis patients. The aim of the present study was to investigate the role of SAS in the promotion of inflammation and oxidative stress and thus in the augmentation of cardiovascular risk in hemodialysis patients. Thirty-seven hemodialysis patients underwent an overnight full polysomnography study. The following morning blood samples were obtained and TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density lipoprotein) were measured. We investigated the correlation of patients' markers of inflammation and oxidative stress with their sleep parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory disturbance index; DI, desaturation index, mean and minimum SpO2 and percentage of sleep time with SpO2 < 90%). TNF-α correlated positively with BMI (r = 0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r = 0.336, P = 0.042) and percentage of sleep time with SpO2 < 90% (r = 0.415, P = 0.012) and negatively with mean SpO2 (r = -0.364, P = 0.027). Myeloperoxidase correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02) and percentage of sleep time with SpO2 < 90% (r = 0.388, P = 0.019). Finally, oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P = 0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO2 <90% (r = 0.389, P = 0.019). These results indicate that, in hemodialysis patients, the severity of SAS and nocturnal hypoxia correlated positively with markers of inflammation and oxidative stress.

Oxidative Stress in Hemodialysis Patients: A Review of the Literature.

Hemodialysis (HD) patients are at high risk for all-cause mortality and cardiovascular events. In addition to traditional risk factors, excessive oxidative stress (OS) and chronic inflammation emerge as novel and major contributors to accelerated atherosclerosis and elevated mortality. OS is defined as the imbalance between antioxidant defense mechanisms and oxidant products, the latter overwhelming the former. OS appears in early stages of chronic kidney disease (CKD), advances along with worsening of renal failure, and is further exacerbated by the HD process per se. HD patients manifest excessive OS status due to retention of a plethora of toxins, subsidized under uremia, nutrition lacking antioxidants and turn-over of antioxidants, loss of antioxidants during renal replacement therapy, and leukocyte activation that leads to accumulation of oxidative products. Duration of dialysis therapy, iron infusion, anemia, presence of central venous catheter, and bioincompatible dialyzers are several factors triggering the development of OS. Antioxidant supplementation may take an overall protective role, even at early stages of CKD, to halt the deterioration of kidney function and antagonize systemic inflammation. Unfortunately, clinical studies have not yielded unequivocal positive outcomes when antioxidants have been administered to hemodialysis patients, likely due to their heterogeneous clinical conditions and underlying risk profile.