Abstract 16854: End-Stage Renal Disease Associated With Metabolic Syndrome: A Study of Biomarkers Relevant to Cardiovascular Risk

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jawed Fareed ◽  
Vinod Bansal ◽  
Debra Hoppensteadt ◽  
Daneyal Syed ◽  
Syed Ahmad

Introduction: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors which contribute to myocardial infarction and stroke in end stage renal disease (ESRD) patients. Several metabolic biomarkers have been identified and their circulating levels provide a better understanding of the pathogenesis of MS/ESRD. The purpose of this investigation is to profile biomarkers of MS in ESRD patients. Materials and Methods: Plasma samples from 87 patients with ESRD undergoing maintenance hemodialysis and 50 normals were collected prior to a routine session. These samples were profiled for metabolic biomarkers using protein chip bioarray technology. The protein chip array was comprised of several biomarkers of MS. All results were compiled in terms of group means +/- 1 SD (SEM) and statistically analyzed. Results: In comparison to the normal samples, the ESRD group showed marked increase in circulating levels of all biomarkers. TNFa (47.4 +/- 18.3 vs 4.1 +/- 1.1 ng/mL) and IL-6 (7.8 +/- 9.1 vs 0.8 +/- 0.4 ng/mL) showed the most pronounced increase. C-peptide (14.5 +/- 4.1 vs 2.8 +/- 1.6 ng/mL), leptin (29.7 +/- 29.2 vs 5.2 +/- 7.9 ng/mL), resistan (16.1 +/- 6.0 vs 2.3 +/- 0.7 ng/mL) and ferritin (274 +/- 57 vs 57 +/- 63 ng/mL) showed a 5-fold increase in the ESRD group compared to normal. PAI-1 (5.4 +/- 5.2 vs 2.9 +/- 2.5 ng/mL), IL-1a (1.3 +/- 1.7 vs 0.35 +/- 0.07 ng/mL) and insulin (32.1 +/- 17.3 vs 17.1 +/- 1.7 ng/mL) showed modest increase in the ESRD patients. The increase in all of the MS biomarkers in the ESRD patients were highly significantly elevated, p <0.05. Conclusion: The specific biochip array for MS allows the selective determination of various biomarkers associated with this syndrome in the ESRD patients and normals. Parallel increase in resistan, insulin, C-peptide, and leptin points to the derangement of glucose metabolism in these patients. Increase IL-1a, TNFa, and ferritin suggests the upregulation of an inflammatory process. PAI-1 increase suggests a fibrinolytic deficit. The parallel derangement of the inflammatory process and metabolic syndrome contributes to the cardiovascular and cerebrovascular complications in these patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Susana Rocha ◽  
Maria João Valente ◽  
Susana Coimbra ◽  
Cristina Catarino ◽  
Petronila Rocha-Pereira ◽  
...  

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.


2010 ◽  
Vol 119 (4) ◽  
pp. 163-174 ◽  
Author(s):  
Bruno Memoli ◽  
Simona Salerno ◽  
Alfredo Procino ◽  
Loredana Postiglione ◽  
Sabrina Morelli ◽  
...  

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.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Sikarin Upala ◽  
Anawin Sanguankeo

Background: Metabolic syndrome (Mets) is documented to increase mortality in the general population. However, there are reports of lower mortality in end stage renal disease (ESRD) patients with obesity. We conducted a meta-analysis to determine the association of all-cause and cardiovascular disease (CVD) mortality, and residual renal function with Mets in ESRD subjects. Objectives: PubMed/MEDLINE, EMBASE, and CENTRAL from their inception to September 2014 were comprehensively searched for eligible studies assessing the effects of the metabolic syndrome in ESRD subjects. Inclusion criterion was ESRD participants who had hemodialysis (HD or peritoneal dialysis (PD). Renal transplant subjects were excluded. Two authors independently assessed article quality and extracted the data. The primary outcome was all-cause mortality and secondary outcomes were CVD death and residual renal function. Results: From 23 full-text articles, 7 studies involving 613 (all-cause mortality), 284 (CVD death) and 383 (residual renal function) participants were included in the meta-analysis that was based on the random effects model. Compared with the non-Mets, ESRD subjects with Mets had no significant difference in risk of all-cause mortality (pooled odds ratio= 1.65; 95% CI, 0.86, 3.17) (figure 1) or CVD death (pooled odds ratio= 1.67; 95% CI, 0.75, 3.69). There was also no difference in residual renal function between the two groups with pooled standard mean difference of -0.26 ml/min/1.73 m2 (95% CI: -0.62, 0.10). Conclusion: Metabolic syndrome is not associated with an increased risk of all-cause or CVD mortality in ESRD patients who underwent HD or PD.


1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.


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.


2007 ◽  
Vol 98 (08) ◽  
pp. 339-345 ◽  
Author(s):  
Johannes Sidelmann ◽  
Mikkel Brabrand ◽  
Robert Pedersen ◽  
Jørgen Pedersen ◽  
Kim Esbensen ◽  
...  

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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