Appropriate Biomarkers For Oxidative Stress In Patients With End Stage Renal Disease

AbstractThe appropriate biomarkers for oxidative stress (OS) in patients with end stage renal disease (ESRD) are important in renal pathology. Patients (56) with ESRD were investigated (35 men and 21 women). Patients, with mean age of 45±17 years, defined education, specific HD duration and calculated body mass index (BMI), were exposed to a polysulphone type HD membrane for approximately 4 hours per HD session, 3 times per week. The control group was composed of 31 healthy volunteers. The total antioxidative capacity (TAC) and the antioxidative (AO) enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), were assessed. Analyses included Randox Crumlin GB; lipid peroxidation (LP) using its end product, malonyldialdehyde (MDA) (fluorimetric); and a LDL-ox immunoassay (Biomedica gruppe, Vienna, Austria). The TAS was higher in ESRD patients before HD (1.63±0.1 mmol/L) compared to the control group (1.23±0.03 mmol/L).

Download Full-text

Associations of Common Variants in HFE and TMPRSS6 Genes with Hepcidin-25 and Iron Status Parameters in Patients with End-Stage Renal Disease

Disease Markers ◽

10.1155/2019/4864370 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Violeta Dopsaj ◽

Aleksandra Topić ◽

Miljan Savković ◽

Neda Milinković ◽

Ivana Novaković ◽

...

Keyword(s):

Renal Disease ◽

Diagnostic Accuracy ◽

End Stage Renal Disease ◽

Iron Status ◽

Transferrin Saturation ◽

Deficiency Anemia ◽

Control Group ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Background. Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. Materials and Methods. Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. Results. ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 μg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p=0.005, partial eta squared=0.09; p=0.027, partial eta squared=0.06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p=0.002, partial eta squared=0.07). Conclusion. Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients.

Download Full-text

Impaired resistance artery function in patients with end-stage renal disease

Clinical Science ◽

10.1042/cs20100277 ◽

2011 ◽

Vol 120 (12) ◽

pp. 525-536 ◽

Cited By ~ 24

Author(s):

Natallia Luksha ◽

Leanid Luksha ◽

Juan Jesús Carrero ◽

Folke Hammarqvist ◽

Peter Stenvinkel ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Nitrosative Stress ◽

Control Group ◽

Strong Impact ◽

Arterial Distensibility ◽

Functional Features ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.

Download Full-text

Serum Sclerostin But Not DKK-1 Correlated with Central Arterial Stiffness in End Stage Renal Disease Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17041230 ◽

2020 ◽

Vol 17 (4) ◽

pp. 1230 ◽

Cited By ~ 1

Author(s):

Chun-Feng Wu ◽

Jia-Sian Hou ◽

Chih-Hsien Wang ◽

Yu-Li Lin ◽

Yu-Hsien Lai ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Arterial Stiffness ◽

Renal Disease ◽

End Stage Renal Disease ◽

Serum Levels ◽

Control Group ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Sclerostin and dickkopf-1 (DKK1) played a role in the development of cardiovascular diseases and arterial stiffness in chronic kidney disease (CKD) patients but with controversial results of patients in end-stage renal disease (ESRD) including hemodialysis (HD) and peritoneal dialysis (PD). This study aimed to examine the association between the mode of dialysis or the values of sclerostin or DKK1 and carotid-femoral pulse wave velocity (cfPWV) in ESRD patients. There were 122 HD and 72 PD patients enrolled in this study. By a validated tonometry system, cfPWV was measured and then segregated patients into values of >10 m/s as the high central arterial stiffness (AS) group and values ≤ 10 m/s as the control group. Serum levels of sclerostin and DKK1 were measured using a commercial enzyme-linked immunosorbent assay kit. Possible risk factors for the development of AS were analyzed by logistic regression analysis. There were 21 (29.2%) of PD and 53 (43.4%) of HD in the high AS group. Compared to patients in the control group, those in the high AS group were older, had more comorbidities, had higher systolic blood pressure, and had higher serum levels of fasting glucose, C-reactive protein, and sclerostin. Levels of sclerostin (adjusted OR 1.012, 95% CI. 1.006–1.017, p = 0.0001) was found to be an independent predictor of high AS in ESRD patients by multivariate logistic regression analysis. Furthermore, receiver operating characteristic curve analysis showed the optimal cut-off values of sclerostin for predicting AS was 208.64 pmol/L (Area under the curve 0.673, 95% CI: 0.603–0.739, p < 0.001). This study showed that serum levels of sclerostin, but not DKK1 or mode of dialysis, to be a predictor for high central AS in ESRD patients.

Download Full-text

Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients

Toxins ◽

10.3390/toxins11070431 ◽

2019 ◽

Vol 11 (7) ◽

pp. 431 ◽

Cited By ~ 4

Author(s):

Djurdja Jerotic ◽

Marija Matic ◽

Sonja Suvakov ◽

Katarina Vucicevic ◽

Tatjana Damjanovic ◽

...

Keyword(s):

Oxidative Stress ◽

Overall Survival ◽

Renal Disease ◽

End Stage Renal Disease ◽

Glutathione S Transferase ◽

Event Modeling ◽

Oxidative Phenotype ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.

Download Full-text

Plasma oxalic acid as a trigger for oxidative processes in end-stage renal disease patients

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.1(69).2021.07 ◽

2021 ◽

pp. 46-53

Author(s):

L. Korol ◽

N. Stepanova ◽

V. Vasylchenko ◽

L. Snisar ◽

L. Lebid ◽

...

Keyword(s):

Oxidative Stress ◽

Oxalic Acid ◽

Renal Disease ◽

End Stage Renal Disease ◽

Malonic Dialdehyde ◽

Sh Groups ◽

Oxidative Processes ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

The present study aimed to evaluate the changes in oxidative stress markers according to the concentration of plasma oxalic acid (POx) in end-stage renal disease (ESRD) patients. Methods. We conducted a cross-sectional observational study involving 72 ESRD patients and 30 relatively healthy individuals who served as a control reference group for evaluation of POx concentration. Among ESRD patients there were 32 hemodialysis (HD) patients and 40 peritoneal dialysis (PD). POx concentration was measured spectrophotometrically using a commercially available kit (MAK315, Sigma, Spain). Malonic dialdehyde (MDA), ceruloplasmin (CP), transferrin (TR), sulfhydryl groups (SH-groups), antioxidant blood capacity (AOC) and total peroxidase activity of erythrocytes (TPA) were measured and the oxidative stress index (OSI) was calculated in all examined patients. Results. A significant increase in POx concentration was observed in ESRD patients compared with healthy volunteers (p < 0.0001). The concentrations of MDA in serum, OSI in erythrocytes and serum of the examined patients were gradually increased, while serum levels of CP, AOC, SH-groups and TPA in erythrocytes, on the contrary, were decreased in accordance with the increasing trend of POx concentrations. Correlation analysis demonstrated a statistically significant direct relationship between POx concentration and MDA (r = 0.57; p <0.0001) and OSI (r = 0.64; p <0.0001). The inverse correlation was determined between POx and antioxidant markers: CP (r = -0.35; p = 0.007), SH-groups in serum (r = -0.3; p = 0.04) and erythrocytes (r = -0.53 ; p <0.0001). Conclusions. The intensity of oxidative-antioxidant balance disorders in the blood of ESRD patients has been associated with the POx concentration: the higher the concentration of POx was the more active oxidative processes and the more pronounced lack of antioxidant protective factors occurred. Further studies are needed to determine the role of POx in the initiation of oxidative stress and chronic inflammation in ESRD patients.

Download Full-text

Haemostatic profiles assessed by thromboelastography in patients with end-stage renal disease

Thrombosis and Haemostasis ◽

10.1160/th10-12-0785 ◽

2011 ◽

Vol 106 (07) ◽

pp. 67-74 ◽

Cited By ~ 31

Author(s):

Andrew Darlington ◽

Josè Luis Ferreiro ◽

Masafumi Ueno ◽

Yoshi Suzuki ◽

Bhaloo Desai ◽

...

Keyword(s):

Renal Disease ◽

Platelet Function ◽

End Stage Renal Disease ◽

Maximum Amplitude ◽

Bleeding Complications ◽

Control Group ◽

Artery Disease ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

SummaryPatients with end-stage renal disease (ESRD) have abnormalities in the cellular and plasmatic systems regulating blood homeostasis, which may contribute to their risk for thrombotic and bleeding complications. However, their relative contributions in this population are poorly understood. The aim of this study was to evaluate the distribution of enzymatic and cellular abnormalities in ESRD patients on haemodialysis as assessed by thromboelastography (TEG®). Whole blood samples were analysed by TEG in ESRD patients (n=70) and in a control group (n=70) of subjects with coronary artery disease. Profiles were constructed considering the maximum amplitude (MA), a marker of platelet function, and reaction time (R), a marker of thrombin generation, values. R values were higher in ESRD patients compared with the control group (8.2 ± 2.8 vs. 5.7 ± 1.9 minutes [min], p <0.0001), while there were no differences in MA (66.7 ± 8.1 vs. 66.2 ± 6.6 mm, p=0.562). Nor mal manufacturer defined coagulation (2–8 min) and aggregation (51–69 mm) parameters were present in 31% of ESRD patients compared with 56% of controls (p=0.006). A hypocoagulable status was observed in 42.9% of ESRD patients compared with 8.9% in the control group (p<0.0001). There were no differences in platelet function, which showed a hyperaggregable status in 41.4% versus 35.7% of cases (p=0.603). Abnormalities in both parameters were observed in 15.7% of ESRD patients versus 1.4% in the control group (p = 0.004), which were more common among older patients (p= 0.005). In conclusion, patients with ESRD have an elevated prevalence of abnormal haemostatic profiles, which may contribute to their elevated risk of bleeding and thrombotic complications.

Download Full-text

Increased Levels of Anaphylatoxin (C5a) and Bradykinin in End-Stage Renal Disease Patients on Maintenance Hemodialysis. Potential Relevance to Heparin Mediated Hemodynamic Responses

Blood ◽

10.1182/blood.v112.11.4079.4079 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4079-4079

Author(s):

Cafer Adiguzel ◽

Vinod Bansal ◽

Josephine Cunanan ◽

Evangelos Litinas ◽

Debra Hoppensteadt ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Sandwich Elisa ◽

Maintenance Hemodialysis ◽

Control Group ◽

Contact Activation ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Abstract Besides the upregulation of inflammatory mediators, end stage renal disease (ESRD) patients maintained on hemodialysis are subjected to periodic exposure to heparin and contact activation due to procedural settings. Recently the presence of a heparin contaminant, namely hypersulfated chondroitin sulfate was linked with the adverse reactions and deaths observed in these patients (Kishmoto, et al. N J Med 2008). To validate this report we measured both the C5a anaphlatoxin and bradykinin levels in ESRD patients prior to and after maintenance hemodialysis. The control group comprised of 40 normal healthy individuals were included to establish the normal level of these mediators. A sandwich ELISA method utilizing a monoclonal antibody which is specific for human C5a and bradykinin were used in these studies. Both the C5a and bradykinin were elevated in pre-dialysis samples from ESRD patients (C5a: 3.2±0.6 ng/ml vs 14.2± 4.6 ng/ml, bradykinin: 6.4±1.8 ng/ml vs 9.3±2.4 ng/ml). Moreover, dialysis itself produced an increase in both the C5a and bradykinin levels. Moreover, the postdialysis samples were further increased, suggesting that dialysis and heparinization itself result in the up-regulation of these mediators. Supplementation of heparin to the plasma also resulted in the generation of both C5a and bradykinin. The plasma samples included in these studies represents patients who were not treateded with the contaminant heparin. Additional studies on in-vitro generation of these markers with contaminated heparin and the isolated contaminant showed that both of these triggered the generation of C5a and bradyknin. These results suggest that both C5a and bradykinin are up-regulated in ESRD patients and this level can be further augmented by dialysis and heparinization. Therefore, additional factors may have contributed to the complex adverse reaction profiles and deaths in patients administrated with contaminated heparin.

Download Full-text

Abstract 16970: Statin Reduce Mortality and Major Cardiovascular Events in End-stage Renal Disease Patient, a Taiwan Cohort Study

Circulation ◽

10.1161/circ.132.suppl_3.16970 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kai-Hung Cheng ◽

Chih-Sheng Chu ◽

Yu-Han Chang ◽

Tzongshi Lu ◽

Wen-Ter Lai

Keyword(s):

Heart Failure ◽

Renal Disease ◽

End Stage Renal Disease ◽

Disease Patient ◽

Control Group ◽

Research Database ◽

Cardiac Events ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Introduction and Hypothesis: Coronary artery disease (CAD) is the leading cause of mortality in end-stage renal disease (ESRD) patients. Vitamin D deficiency is common in patients with ESRD, and therapeutic use of Calcitriol may improve cardiovascular outcomes. Studies indicate that Statin can reduce incidences of major adverse cardiac events (MACE), and mortality in CAD. However, both 4D and AURORA studies report Statin cannot reduce MACE and mortality in ESRD patients. The goal of our study is to assess the effects of Statin and Calcitriol administration in ESRD. Methods: A total of 837 subjects selected from 12342 ESRD patients from Taiwan’s National Health Insurance Research Database were stratified into four groups (Control (n=498), S: Statin (n=131), C: Calcitriol (n=130), SC: Statin and Calcitriol (n=78)). We analyze their mediation history for twelve years since their ESRD diagnosed. One way ANOVA with Bonferroni correction, chi-square test, fisher's exact and Cox proportional hazard regression were used for statistics. Statistical significances were set at a P< 0.05. Results: Our data (Adjusted Hazard Ratio (HR), 95% Confidence Interval (CI)) showed that mortality was significant reduced when treated with Statin (0.6, 0.43-0.84), Calcitriol, (0.5, 0.35-0.72), Statin and Calcitriol (0.51, 0.31-0.82) in comparison with control group, respectively. Interestingly, these significant changes were first observed at 10th-year in S and SC groups, but at 12th-year in C group. In addition, Statin reduced MACE (0.55, 0.37-0.81) and heart failure (0.51, 0.27-0.95) incidences. Furthermore, Calcitriol also reduced MACE (0.37, 0.23-0.59), stroke (0.34, 0.16-0.72) and heart failure (0.46, 0.25-0.86) incidences as well as SC treatment decreased MACE (0.38, 0.22-0.68), stroke (0.45, 0.21-0.97), and heart failure (0.26, 0.09-0.73) incidences. Conclusions: Our data show for the first time that Statin alone can reduce incidences of mortality, MACE and heart failure but not stroke in ESRD. And, combination of Statin and Calcitriol provides best outcomes in ESRD patients with heart failure among these groups. This finding may provide important information in developing therapeutic strategies for the roles of Statin and Calcitriol in ESRD.

Download Full-text

Effect of α-Lipoic Acid on Oxidative Stress in End-Stage Renal Disease Patients Receiving Intravenous Iron

ISRN Nephrology ◽

10.1155/2014/634515 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Arif Showkat ◽

William R. Bastnagel ◽

Joanna Q. Hudson

Keyword(s):

Oxidative Stress ◽

Renal Disease ◽

Lipoic Acid ◽

End Stage Renal Disease ◽

Transferrin Saturation ◽

Lipid Hydroperoxide ◽

Increased Risk ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. The aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, α-lipoic acid. This is an open-label, crossover study. 125 mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600 mg of α-lipoic acid was given orally prior to IV SFG. Blood samples were collected at defined time periods for F2-isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African-American ESRD subjects: 50% male; mean age 45±9 years; mean hemoglobin 13±1 g/dL; ferritin 449±145 ng/mL; transferrin saturation 27±4%. There were no significant differences in iron indices between the two visits after IV SFG. MDA, FIP, and LHP increased significantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of α-lipoic acid was associated with a greater increase in oxidative stress.

Download Full-text