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.

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 ◽  
Vol 11 (1) ◽  
Author(s):  
Susana Rocha ◽  
Maria João Valente ◽  
Susana Coimbra ◽  
Cristina Catarino ◽  
Petronila Rocha-Pereira ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
End Stage Renal Disease ◽  
Inflammatory Biomarkers ◽  
Genotype Distribution ◽  
Pentraxin 3 ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage ◽  
Circulating Levels ◽  
Esrd Patients

AbstractChronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The circulating levels of the inflammatory biomarkers interleukin 6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients, and are associated with the progression of the disease and with higher risk for cardiovascular events, the major cause of death in CKD patients. Our aim was to study how specific polymorphisms of IL6 and PTX3 encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. Methodology included the analysis of two single nucleotide polymorphisms (SNP), namely the IL6 (rs1800795) polymorphism in the promoter region (-174G > C), and the PTX3 (rs2305619) polymorphism in the intron 1 (+ 281A > G), which were analyzed in ESRD patients on dialysis and in a group of heathy individuals. The allelic frequencies, genotype distribution and their association with circulating levels of the inflammatory markers C-reactive protein (CRP), IL6, growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients. Events of death were recorded along one year, to assess the association of the studied SNPs with all-cause mortality and the inflammatory biomarkers, in ESRD patients. Results showed that the allelic frequencies and genotype distribution for IL6 and PTX3 SNPs in the control group and ESRD patients were similar and in agreement with other European reports. For the IL6 polymorphism, we found a trend towards higher levels of high-sensitivity (hs) CRP, IL6 and PTX3 in the homozygous genotypes; the CC genotype also showed the highest levels of GDF15. The mortality rate after the 1-year follow-up was 10.4%. The CC genotype (IL6 SNP) was associated to a higher risk of mortality and deceased patients carrying this genotype also showed the highest levels of hsCRP. Regarding the studied PTX3 SNP, the AA genotype was linked to an enhanced inflammatory response, showing the highest values of hsCRP and IL6. Nevertheless, this genotype had no significant impact on the mortality rate. In conclusion, both studied SNPs seem to modulate the inflammatory response in ESRD and may, therefore, be determinant on disease progression and patients’ outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

scholarly journals Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Maria João Valente ◽  
Susana Rocha ◽  
Susana Coimbra ◽  
Cristina Catarino ◽  
Petronila Rocha-Pereira ◽  
...  
Keyword(s):  
End Stage Renal Disease ◽  
Renal Fibrosis ◽  
Pentraxin 3 ◽  
Dialysis Patients ◽  
Inflammatory Biomarker ◽  
Multiple Risk Factors ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.

Longitudinal Causal Effects of Normalized Protein Catabolic Rate on All-Cause Mortality in Patients with End-Stage Renal Disease: Adjusting for Time-varying Confounders Using G-estimation Method

2020 ◽  
Author(s):  
Mohammad Aryaie ◽  
Hamid Sharifi ◽  
Azadeh Saber ◽  
Maryam Nazemipour ◽  
Mohammad Ali Mansournia
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Weibull Model ◽  
Time Varying ◽  
Catabolic Rate ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Protein Catabolic Rate

Abstract This study aimed to estimate causal effect of normalized protein catabolic rate (nPCR) on mortality among end stage renal disease (ESRD) patients in the presence of time-varying confounding affected by prior exposure using g-estimation. Information about 553 ESRD patients was retrospectively collected over 8 years, from 2011 to 2019, from hemodialysis facilities at Kerman, southeast of Iran. nPCR was dichotomized to < 1.2 versus ≥ 1.2 g/kg per day. Then standard time-varying accelerated failure time (AFT) Weibull model was built, and results were compared with those generated by g-estimation. After appropriately adjusting for time-varying confounders, weighted g-estimation yielded 78% shorter survival time (95% confidence interval [95% CI]: -81% to -73%) in patients under continuous nPCR < 1.2 than those who had nPCR ≥ 1.2 g/kg per day during the follow-up, though it was 18% (95% CI: -57% to +54%) in Weibull model. Moreover, the hazard ratio estimates of 4.56 (95% CI: 3.69 to 5.37), and 1.20 (95% CI: 0.66 to 2.17) were obtained by weighted g-estimation and Weibull model, respectively. G-estimation indicated that inadequate dietary protein intake characterized by nPCR increases all-cause mortality among ESRD patients, but the Weibull model provided a substantially biased effect estimate towards the null.

scholarly journals End-Stage Renal Disease and Critical Limb Ischemia: A Deadly Combination?

2012 ◽  
Vol 101 (2) ◽  
pp. 138-143 ◽  
Author(s):  
F. Biancari ◽  
E. Arvela ◽  
M. Korhonen ◽  
M. Söderström ◽  
K. Halmesmäki ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Disease ◽  
Lower Limb ◽  
End Stage Renal Disease ◽  
Bypass Surgery ◽  
Independent Predictor ◽  
All Cause Mortality ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Objectives: This study was planned to evaluate the prognostic impact of end-stage renal disease (ESRD) in patients with critical leg ischemia (CLI) undergoing infrainguinal revascularization. Materials and Methods: 1425 patients who underwent infrainguinal revascularization for CLI were the subjects of the present analysis. Ninety-five patients had ESRD (eGFR < 15 ml/min/m2), and of them 66 (70%) underwent percutaneous transluminal angioplasty and 29 (30%) underwent bypass surgery. Results: ESRD patients had significantly lower overall survival (at 3-year, 27.1% vs. 59.7%, p < 0.0001), leg salvage (at 3-year, 57.7% vs. 83.0%, p<0.0001), and amputation free survival (at 3-year, 16.2% vs. 52.9%, p < 0.0001) than patients with no or less severe renal failure. The difference in survival was even greater between 86 one-to-one propensity matched pairs (at 3-year, 23.1% vs. 67.3%, p < 0.0001). ESRD was an independent predictor of all-cause mortality (RR 2.46, 95%CI 1.85–3.26). Logistic regression showed that age ≥ 75 years was the only independent predictor of 1-year all-cause mortality (OR 4.92, 95%CI 1.32–18.36). Classification and regression tree analysis showed that age ≥ 75 years and, among younger patients, bypass surgery for leg ulcer and gangrene were associated with significantly higher 1-year mortality. Conclusions: Lower limb revascularization in patients with CLI and end-stage renal failure is associated with favourable leg salvage. However, these patients have a very poor survival and this may jeopardize any attempt of revascularization. Further studies are needed to identify ESRD patients with acceptable life expectancy and who may benefit from lower limb revascularization.

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.

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.

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