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

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Violeta Dopsaj ◽  
Aleksandra Topić ◽  
Miljan Savković ◽  
Neda Milinković ◽  
Ivana Novaković ◽  
...  

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.

2011 ◽  
Vol 120 (12) ◽  
pp. 525-536 ◽  
Author(s):  
Natallia Luksha ◽  
Leanid Luksha ◽  
Juan Jesús Carrero ◽  
Folke Hammarqvist ◽  
Peter Stenvinkel ◽  
...  

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.


Author(s):  
Chun-Feng Wu ◽  
Jia-Sian Hou ◽  
Chih-Hsien Wang ◽  
Yu-Li Lin ◽  
Yu-Hsien Lai ◽  
...  

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.


2011 ◽  
Vol 106 (07) ◽  
pp. 67-74 ◽  
Author(s):  
Andrew Darlington ◽  
Josè Luis Ferreiro ◽  
Masafumi Ueno ◽  
Yoshi Suzuki ◽  
Bhaloo Desai ◽  
...  

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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4079-4079
Author(s):  
Cafer Adiguzel ◽  
Vinod Bansal ◽  
Josephine Cunanan ◽  
Evangelos Litinas ◽  
Debra Hoppensteadt ◽  
...  

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.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kai-Hung Cheng ◽  
Chih-Sheng Chu ◽  
Yu-Han Chang ◽  
Tzongshi Lu ◽  
Wen-Ter Lai

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Arif Showkat ◽  
William R. Bastnagel ◽  
Joanna Q. Hudson

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.


2015 ◽  
Vol 16 (4) ◽  
pp. 287-290
Author(s):  
Petar Dejanov ◽  
Beti Dejanova

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).


2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 298-302
Author(s):  
Robert H. Mak ◽  
Wai Cheung

Cachexia is common in end-stage renal disease (ESRD) patients, and it is an important risk factor for poor quality of life and increased mortality and morbidity. Chronic inflammation is an important cause of cachexia in ESRD patients. In the present review, we examine recent evidence suggesting that adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor necrosis factor α, interleukin-6, and interleukin-1β may play important roles in uremic cachexia. We also review the physiology and the potential roles of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD. Understanding the molecular pathophysiology of these novel hormones in ESRD may lead to novel therapeutic strategies.


Author(s):  
Hyeon-Ju Lee ◽  
Youn-Jung Son

Hemodialysis is the most common type of treatment for end-stage renal disease (ESRD). Frailty is associated with poor outcomes such as higher mortality. ESRD patients have a higher prevalence of frailty. This systematic review and meta-analysis aimed to identify the prevalence and associated factors of frailty and examine whether it is a predictor of mortality among ESRD patients undergoing hemodialysis. Five electronic databases including PubMed, Embase, CINAHL, Web of Science, and Cochrane Library were searched for relevant studies up to 30 November 2020. A total of 752 articles were found, and seven studies with 2604 participants in total were included in the final analysis. The pooled prevalence of frailty in patients with ESRD undergoing hemodialysis was 46% (95% Confidence interval (CI) 34.2−58.3%). Advanced age, female sex, and the presence of diabetes mellitus increased the risk of frailty in ESRD patients undergoing hemodialysis. Our main finding showed that patients with frailty had a greater risk of all-cause mortality compared with those without (hazard ratio (HR): 2.02, 95% CI: 1.65−2.48). To improve ESRD patient outcomes, healthcare professionals need to assess the frailty of older ESRD patients, particularly by considering gender and comorbidities. Comprehensive frailty screening tools for ESRD patients on hemodialysis need to be developed.


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