Differential Modulation of Cytokines by VEGF In End Stage Renal Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5187-5187
Author(s):  
Vinod Bansal ◽  
Debra Hoppensteadt ◽  
Evangelos Litinas ◽  
Indermohan Thethi ◽  
Jawed Fareed

Abstract Abstract 5187 Vascular endothelial growth factor (VEGF) mediates nitric oxide dependent angiogenic effects contribute to the inflammatory responses. VEGF is upregulated in ESRD and contributes to the cardiovascular dysfunction in ESRD. VEGF is also upregulated by erythropoietin which is commonly used in the management of ESRD patients. With the availability of BioChip Array Technology, a multiparametric screening of inflammatory mediators/cytokines can be measured and relevance of VEGF can be established. Utilizing the Randox Biochip technology, we profiled the plasma samples from 53 ESRD patients to determine their relevance to VEGF levels. Pre-dialysis samples from 53 male and female ESRD patients on maintenance hemodialysis were analyzed using a cytokine biochip for VEGF, IL2, IL4, IL6, IL8, IFNG1, TNF, IL1, MCP-1 and EGF. In addition, NO, asymmetric dimethyl arginine (ADMA), serotonin and functional microparticles levels were also measured. A group of 50 normal healthy males and females constituted the control group. The circulating levels of VEFG and mediators were compared with the normals. In addition, VEGF levels were compared with the other mediators. In comparison to the normals, ESRD patients exhibited decreased levels of IL4, IL8, TNF and EGF, which ranged from 20–210%. Increased levels of IL2, IL6, IL10, IFNG1, IL1 and MCP-1 were noted (20-350%). NO levels were also increased, however ADMA remained unchanged. Both the serotonin and microparticle levels were also elevated in comparison to the normals (p>0.05) VEGF levels showed wide variation, however on a cumulative basis a 30–210% increase in VEGF was noted. Except for the MCP-1, the correlation of VEGF with other inflammatory markers was relatively poor (r2=<0.25). These results show that ESRD patients can be profiled for various inflammatory mediators. VEGF levels were markedly increased, however only MCP-1 levels correlated well with the increase in VEGF levels. Additional studies are warranted to clarify the regulatory role of VEGF and other mediators on inflammatory cytokines and cellular activation in ESRD. Disclosures: No relevant conflicts of interest to declare.

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.


2016 ◽  
Vol 15 (1) ◽  
pp. 61-65
Author(s):  
Kumar Roka ◽  
Pratibha Bista Roka

Introduction: End stage renal disease presents with multiple clinical and systemic manifestations. The aim of the present study was to identify the early cardiac and other morbidities in end stage renal disease (ESRD) patients who were under maintenance hemodialysis.Methods: This was an observational, prospective study conducted in fifty established ESRD patients of 20 to 74 years under maintenance hemodialysis in Nephrology unit of Shree Birendra Hospital. Clinical examination, laboratory parameters, electrocardiogram and echocardiography findings were used to identify the morbidities. Results: Among all patients enrolled in the study 88.7% had anemia, 64.2 % systolic murmurs, 62.26 % pedal edema, 73.6 % fatiguability, 71.7 % angina, 24.4 % palpitations and 13.2 % had breathlessness on exertion.  62.26% of the patients had hypertension and 13.20 % had diabetes. In the electrocardiogram, prolonged QTc was observed in 10.4%, followed by T wave inversion in 9.4 % and finally low voltage complex comprised 7.6 %. The echocardiogram showed left ventricular diastolic dysfunction in 58.5 %, left ventricular hypertrophy (overall type) 49 % and valvular lesion like mitral regurgitation and tricuspid regurgitation 83 % and 58.5 % respectively. Conclusion: Cardiac co-morbidities are common in patients diagnosed with ESRD on maintenance hemodialysis.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Małgorzata Maraj ◽  
Beata Kuśnierz-Cabala ◽  
Paulina Dumnicka ◽  
Katarzyna Gawlik ◽  
Dorota Pawlica-Gosiewska ◽  
...  

Over 50% of end-stage renal disease (ESRD) patients die of cardiovascular disease. ESRD patients treated with maintenance hemodialysis are repeatedly exposed to oxidative stress. The aim of the study was to find the relationship between lifestyle factors, nutritional status, calcium-phosphate metabolism, and selected redox parameters such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), uric acid (UA), and total antioxidant capacity expressed as ferric reducing antioxidant power (FRAP). The study included 97 ESRD hemodialysis patients and 42 controls with no renal disease. Patients were asked to complete a questionnaire which gathered information on their physical activity, hours of sleep, smoking, and frequency of fruit and vegetable intake; the blood samples were then drawn before the midweek dialysis session. The ESRD patients had lower levels of GR, GPx, and SOD activity, a lower level of FRAP, and a higher UA concentration than the control group. The FRAP value decreased with age (ρ=−0.32, p=0.001); smokers had a significantly lower SOD activity in comparison to nonsmokers (p=0.03). In the ESRD patients, FRAP and UA correlated with both albumin (ρ=0.26, p=0.011; ρ=0.41, p=0.006, respectively) and prealbumin (ρ=0.34, p≤0.001; ρ=0.28, p=0.006, respectively), whereas UA, GR, GPx, and SOD correlated with calcium, UA, GR, and GPx with phosphate level. Based on the findings, there are weak associations between nutritional status and selected redox parameters in hemodialyzed patients. Further studies are needed to establish if diet modifications and adequate nutritional status can positively impact the antioxidant capacity in this group of patients.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5186-5186
Author(s):  
Vinod Bansal ◽  
Rachael Davis ◽  
Evangelos Litinas ◽  
Debra Hoppensteadt ◽  
Indermohan Thethi ◽  
...  

Abstract Abstract 5186 End-Stage Renal Disease (ESRD) is a complex syndrome in which systemic vascular pathophysiologic changes contribute to adverse cardiovascular and cerebrovascular manifestations. Cardiovascular disease alone is present in over 60% of patients with ESRD and contributes heavily to mortality among this population. Given that inflammatory and hemostatic aberrations contribute to the overall pathogenesis of the syndrome, the purpose of this study is to profile several inflammatory mediators in order to better understand their role in the underlying mechanism of vascular changes in ESRD. Plasma samples from 49 patients with ESRD were collected prior to maintenance hemodialysis sessions. A group of 56 normal individuals, both male and female, was included as control. Cerebral Array II chips were used in the Randox® system to simultaneously measure Neuron Specific Enolase (NSE), Neutrophil Gelatinase-associated Lipocalin (NGAL), Soluble Tumor Necrosis Factor Receptor I (TNFRI), D-Dimer (DD), Thrombomodulin (TM), and C-reactive protein (CRP). The Randox® Evidence Investigator™ is a new biochip array technology that utilizes multiple discrete test regions of immobilized antibody to simultaneously quantify multiple markers from a single patient plasma sample based on the light signal generated from each test region. The data was statistically analyzed using the Mann-Whitney U test (two-tailed with Gaussian approximation). As compared to the normal individual, all of the markers studied showed an upregulation in patients with ESRD. Most notably, TNFRI showed a 19.8 fold increase in patients with ESRD (mean 7.8 ± 2.8 ng/ml, range 0.8 to 13.7) compared to the control (mean 0.4 ± 0.2, range 0.1 to 1.0). TM was increased 5.2 fold (mean 6.5 ± 2.6, range 0.7 to 14.1) compared to control (mean 1.2 ± 0.4, range 0.6 to 2.3). Also, NGAL showed a 4.6 fold increase (mean 1390 ± 257, range 406 to 1729), compared to control (mean 299 ± 99, range 115 to 603), and CRP a 4.2 fold increase (mean 5.7 ± 4.2 ug/ml, range 0.6 to 13.2) compared to control (mean 1.4 ± 1.7, range 0.2 to 11.4). DD and NSE were also increased 3.0 and 1.8 fold respectively. These studies show that some newer markers such as TNFRI, NGAL and NSE are upregulated in ESRD. The marked increase in TM is highly suggestive of endothelial damage. Similarly, the increase in TNFRI supports a state of increased cellular damage. The elevations in NGAL and CRP imply a state of increased inflammation and indicate a polypathologic process, which may predispose ESRD patients to both cardiovascular and cerebrovascular thromboembolic events. Finally, this study further validates the role of endothelial damage and endogenous thrombotic processes in ESRD as evidenced by the increased levels of TM and DD. However, the clinical significance of these markers still needs to be further explored. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 1 (2) ◽  

Objective: The arterial needle placement in arteriovenous fistula (AVF) can either be antegrade (in the direction of blood flow or pointing towards the heart) or retrograde (against the direction of blood flow) while venous needle placement should always be in the same direction as the blood flow. This study determined the effects of arterial needle placement in the arteriovenous fistula on dialysis adequacy of End-Stage Renal Disease (ESRD) patients undergoing maintenance hemodialysis in United Candelaria Doctors Hospital - Nephro Synergies Inc. (UCDHNSI) Hemodialysis Center. Methods: A randomized controlled trial design was used in the study. A total of 20 non-diabetic, non-cardiac patients on maintenance hemodialysis for more than 6 months were randomized either to the intervention group (patients’ AVF were cannulated in a retrograde manner) or the control group (patients’ AVF were cannulated in an antegrade manner). Urea reduction ratio (URR) and Kt/V as well as access recirculation percentage were used to determine dialysis adequacy. Pre-dialysis, in the first 30 minutes of dialysis initiation and post-dialysis blood samples were obtained in each patient in 6 succeeding hemodialysis considering dialyzer reuse up to fifth reuse. Means were compared by independent t-test. Results: The findings of the study revealed that the mean URR and Kt/V of the subjects cannulated in retrograde manner and antegrade manner were 69.35% and 1.45, and 74.65% and 1.70, respectively. The mean access recirculation percentage of the subjects was 4.65% in the intervention group and 3.02% in the control group. There was a significant difference on URR and Kt/V of the subjects using retrograde and antegrade arterial needle placement in 6 succeeding hemodialysis sessions. There was no significant difference on access recirculation percentage of the subjects using retrograde and antegrade arterial needle placement in 6 succeeding hemodialysis sessions. Conclusions: Antegrade arterial needle placement provides more adequate hemodialysis than retrograde arterial needle placement in terms of URR and Kt/V values among non-diabetic, non-cardiac patients undergoing maintenance hemodialysis in 6 succeeding hemodialysis sessions. The directions of the arterial needle either retrograde and antegrade did not have significant effects on access recirculation.


2020 ◽  
Author(s):  
Shaohui Ma ◽  
Ming Zhang ◽  
Yang Liu ◽  
Dun Ding ◽  
Peng Li ◽  
...  

Abstract Background End-stage renal disease (ESRD) patients are at substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there did not provide an uncontested result whether cognition was improved or worsened during dialysis. Methods To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), ESRD patients before dialysis initiation (bESRD) and those undergoing maintenance hemodialysis (mESRD). All ESRD patients performed a serious of blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K + and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in mESRD and bESRD groups. Results Neuropsychological analysis showed mESRD exhibited greater cognitive function than bESRD, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the bESRD and mESRD than the HCs. Besides, lower normalized clustering coefficient was in bESRD relative to the HCs and mESRD. For the GLMs analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in bESRD. Conclusions Our study revealed that dialysis had a limited effect on cognitive improvement. Cystatin C may be a risk feature of cognitive decline of bESRD.


2020 ◽  
Author(s):  
Shaohui Ma ◽  
Ming Zhang ◽  
Yang Liu ◽  
Dun Ding ◽  
Peng Li ◽  
...  

Abstract Background: End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn’t an uncontested result whether cognition was improved or worsened during dialysis.Methods: To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group.Results: Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group.Conclusions: Our study revealed that dialysis had a limited effect on cognitive improvement.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Feng Zhu ◽  
Jiao Xu ◽  
Mei Yang ◽  
Haitao Chi

The aim of this research was to explore the relationship between depression and brain nerve function in patients with end-stage renal disease (ESRD) and long-term maintenance hemodialysis (MHD) based on watershed segmentation algorithm using diffusion tensor imaging (DTI) technology. A total of 29 ESRD patients with depression who received MHD treatment in the hemodialysis center of hospital were included as the research subjects (case group). A total of 29 healthy volunteers were recruited as the control group, and a total of 29 ESRD patients with depression and brain lesions were recruited as the control group (HC group). Within 24 h after hemodialysis, the blood biochemical indexes were collected before this DTI examination. All participants completed the neuropsychological scale (MoCA, TMT A, DST, SAS, and SDS) test. The original DTI data of all subjects were collected and processed based on watershed segmentation algorithm, and the results of automatic segmentation according to the image were evaluated as DSC = 0.9446, MPA = 0.9352, and IOU = 0.8911. Finally, the average value of imaging brain neuropathy in patients with depression in the department of nephrology was obtained. The differences in neuropsychological scale scores (PSQI, MoCA, TMTA, DST, SAS, and SDS) between the two groups were statistically significant ( P < 0.05 ). The differences of FA values in all the white matter partitions of Fu organs, except the cingulum of hippocampus (CgH) between the two groups, were statistically significant ( P < 0.05 ). ESRD and DTI quantitative detection under the guidance of watershed segmentation algorithm in MHD patients showed that ESRD patients can be early identified, so as to carry out psychological nursing as soon as possible to reduce the occurrence of depression, and then protect the brain nerve to reduce brain neuropathy.


2021 ◽  
Author(s):  
Abolhassan Seyedzadeh ◽  
Mohamad Reza Tohidi ◽  
Sima Golmohamadi ◽  
Hamid Reza Omrani ◽  
Mohammad Saleh Seyedzadeh ◽  
...  

Objectives: The current study aimed to determine the prevalence of Renal Osteodystrophy (ROD) and its related factors in a group consisting of End-Stage Renal Disease (ESRD) patients undergoing maintenance hemodialysis. Methods: One hundred twenty –eight ESRD patients (52 men & 76 women) with a mean age of 59.3 years old undergoing maintenance hemodialysis at Imam Reza Referral Hospital, were included in this cross-sectional study. Thereafter, serum parathyroid hormone (PTH) levels were measured, and the range of 150 to 300 pg/mL was determined as the desirable range for the values. Values lower or higher than this range were used to determine ROD. Furthermore, this study investigated the association of ROD with clinical and laboratory variables (age at the onset of renal failure, hemodialysis sessions per week, clinical symptoms associated with renal osteodystrophy, and serum calcium and phosphate levels). Results: ROD was diagnosed in 93 patients (72.7%) out of 128 patients studied. Of them, 53 (41.4%) patients had PTH levels above 300 pg/mL (high bone turnover, HTO group) and 40 patients (31.3%) had PTH levels below 150 pg/mL (low bone turnover, LTO group). No statistically significant difference was detected in terms of ROD-related clinical findings (P=0.11), age at the time of ESRD diagnosis (P=0.2), and number of hemodialysis sessions per week (P=0.2). Hyperphosphatemia (52 patients, 57.1%) was more prevalent in ROD group compared with 11 patients (31.4%) included in the group without ROD (P=0.004). Conclusion: The prevalence rate of ROD in this study was found to be significant, and it was largely consistent with the rate reported in the research previously performed in some Asian countries. Hyperphosphatemia were laboratory variables closely related to ROD.


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.


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