A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6

2010 ◽  
Vol 119 (4) ◽  
pp. 163-174 ◽  
Author(s):  
Bruno Memoli ◽  
Simona Salerno ◽  
Alfredo Procino ◽  
Loredana Postiglione ◽  
Sabrina Morelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Disease ◽  
Interleukin 6 ◽  
End Stage Renal Disease ◽  
Human Hepatocytes ◽  
Fetuin A ◽  
Stage Renal Disease ◽  
End Stage ◽  
Circulating Levels ◽  
Esrd Patients

Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.

scholarly journals Interleukin 6 (rs1800795) and Pentraxin 3 (rs2305619) Polymorphisms - Association with Inflammation and All-Cause Mortality in End-stage-renal Disease Patients on Dialysis

2021 ◽  
Author(s):  
Susana Rocha ◽  
Maria João Valente ◽  
Susana Coimbra ◽  
Cristina Catarino ◽  
Petronila Rocha-Pereira ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Renal Disease ◽  
Interleukin 6 ◽  
End Stage Renal Disease ◽  
Pentraxin 3 ◽  
Allelic Frequencies ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Abstract Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The inflammatory biomarkers interleukin-6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients and associated with progression of the disease and higher risk for cardiovascular events, the major cause of death in these patients. Our aim was to study how the polymorphisms of their encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. We analyzed two single nucleotide polymorphisms (SNP), the IL6 (rs1800795) polymorphism in the promoter region (-174G/C), and the PTX3 polymorphism in the intron 1 (+ 281A/G), in ESRD patients on dialysis and in heathy individuals. The allelic frequencies, genotype distribution and their association with the circulating levels of the inflammatory markers high sensitivity C-reactive protein (hsCRP), interleukin (IL6), growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients; events of death were recorded along one year to evaluate all-cause mortality and the association between inflammation and the studied polymorphisms. The allelic frequencies and genotyping distribution for IL6 and PTX3 in controls and ESRD patients were similar and in agreement with European reports. For the IL6 polymorphism, we found an association of the GG and CC genotype with higher IL6 levels; the CC genotype showed also high PTX3, hsCRP and GDF15 levels. For the PTX3 polymorphism, the AA genotype was linked to the highest values of hsCRP and IL6. The mortality rate after 1-year follow-up was 10.4%. The CC genotype (IL6 polymorphism), in deceased patients, was associated to increased levels of hsCRP, IL6 and PTX3, with low levels of GDF15 and with a highest mortality risk. The AA genotype for PTX3 polymorphism, in spite of the enhancement in inflammation, showed no significant impact on mortality. Our results show that the CC genotype of the IL6 polymorphism was associated with an enhanced inflammatory state and a poorer survival rate. Both IL6 and PTX3 polymorphisms seem to modulate the inflammatory response and, therefore, disease progression and outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls

2019 ◽  
Vol 10 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jelena Munjas ◽  
Miron Sopić ◽  
Nataša Bogavac-Stanojević ◽  
Milica Kravljača ◽  
Milica Miljković ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Healthy Controls ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Resistin Mrna

Background: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. Aims: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. Methods: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. Results: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). Conclusion: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Adipokines and Gut Hormones in End-Stage Renal Disease

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 298-302
Author(s):  
Robert H. Mak ◽  
Wai Cheung
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Poor Quality ◽  
Mortality And Morbidity ◽  
Novel Therapeutic Strategies ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

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.

scholarly journals Prevalence and Associated Factors of Frailty and Mortality in Patients with End-Stage Renal Disease Undergoing Hemodialysis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 18 (7) ◽  
pp. 3471
Author(s):  
Hyeon-Ju Lee ◽  
Youn-Jung Son
Keyword(s):  
Systematic Review ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Associated Factors ◽  
Meta Analysis ◽  
Screening Tools ◽  
Cochrane Library ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

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.

Fibrin clot structure in patients with end-stage renal disease

2007 ◽  
Vol 98 (08) ◽  
pp. 339-345 ◽  
Author(s):  
Johannes Sidelmann ◽  
Mikkel Brabrand ◽  
Robert Pedersen ◽  
Jørgen Pedersen ◽  
Kim Esbensen ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Healthy Controls ◽  
Structure Characteristics ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Fibrin Structure ◽  
Plasma Markers ◽  
Fibrin Clots

SummaryFibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD).These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p<0.001), less compactable (p<0.001), and less susceptible to fibrinolysis (p<0.001) than clots from controls.The maximum rate of turbidity increase was also higher for the patients than controls (p<0.001), and scan-ning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p<0.001). Patients had higher plasma concentrations of fibrinogen, C-reative protein and interleukin 6 than controls.These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.

scholarly journals Single-Dose Pharmacokinetics, Safety, and Tolerability of Albinterferon Alfa-2b in Subjects with End-Stage Renal Disease on Hemodialysis Compared to Those in Matched Healthy Volunteers

2010 ◽  
Vol 55 (2) ◽  
pp. 473-477 ◽  
Author(s):  
Denise B. Serra ◽  
Haiying Sun ◽  
Sylwia Karwowska ◽  
Jens Praestgaard ◽  
Atef Halabi ◽  
...  
Keyword(s):  
Renal Disease ◽  
Healthy Volunteers ◽  
End Stage Renal Disease ◽  
Hepatitis C Virus Infection ◽  
Time Curve ◽  
And Gender ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Laboratory Adverse Event

ABSTRACTAlbinterferon alfa-2b (albIFN) is being developed, in combination with ribavirin, for the treatment of hepatitis C virus infection. This study was designed to evaluate the pharmacokinetics, safety, and tolerability of a 900-μg dose of albIFN administered as a single subcutaneous injection in end-stage renal disease (ESRD) patients on hemodialysis and matched healthy volunteers (by age [±5 years], weight [±5 kg], and gender). The maximum concentration in plasma (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0-∞) were 42.8 ± 14.0 ng/ml and 16,414 ± 4,203 ng·h/ml, respectively, for healthy volunteers, while theCmaxand AUC0-∞were 49.9 ± 20.9 ng/ml and 18,919 ± 8,008 ng·h/ml, respectively, for ESRD patients. The geometric least-squares mean ratios were 1.15 (90% confidence interval [CI], 0.78, 1.68) forCmaxand 1.11 (90% CI, 0.83, 1.48) for AUC0-∞. Adverse events were as expected for an interferon (e.g., flu-like symptoms), with the main laboratory adverse event being a decline in total white blood cell count, which was specifically related to a decline in the neutrophil count. This effect was somewhat greater in the ESRD patients, with the maximal decreases in neutrophil counts from those at the baseline being (−2.6 ± 0.32) × 109and (−2.19 ± 0.58) × 109cells/liter for the ESRD patients and the healthy volunteers, respectively. This study indicates no significant effect of renal failure on the pharmacokinetics of albIFN. Safety and tolerability were as expected for an interferon.

A preliminary investigation of the Partners in Health scale measurement properties in patients with end stage renal disease

2017 ◽  
Vol 23 (3) ◽  
pp. 288 ◽  
Author(s):  
Claire Baxter ◽  
Andrea Morello ◽  
David Smith ◽  
Lynda Norton ◽  
David Bentley
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Structured Interview ◽  
Face Validity ◽  
Measurement Properties ◽  
Self Management ◽  
Management Capacity ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

End-stage renal disease (ESRD) is becoming more prevalent in Australia. As a result, strategies to improve quality of life when living with ESRD are becoming increasingly important. The Flinders Program has been developed to help support and increase the self-management capacity of people living with chronic disease. The Partners in Health (PIH) scale is a self-management capacity assessment tool, which is an integral element of the Flinders Program. The primary aim of this study was to investigate the preliminary measurement properties of the PIH scale within the ESRD population. Forty participants took part in the study, which involved survey assessments at baseline and follow up and a semi-structured interview. Results indicated that the PIH scale had good internal reliability (α=0.85), moderate test-retest reliability (r=0.33) and face validity in ESRD patients. Areas for improving the instrument or data collection process were identified through qualitative interviews, and implications are discussed specific to ESRD patients.

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