Background and Aims
End stage renal disease (ESRD) is a complex progressive medical condition that affects multiple organ systems. Given the high risk of morbidity and mortality of ESRD as well as its rising incidence, it is critical to understand the relevance of thromboinflammatory biomarkers in disease development and progression of kidney dysfunction. The purpose of this study is to profile the levels of thromboinflammatory biomarkers in ESRD patients including D-Dimer, C-reactive protein (CRP), von Willebrand factor (vWF), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI). In addition, the levels of anti-PF4 IgG and endogenous circulating glycosaminoglycans (GAGs) were measured.
Method
Citrated plasma samples were collected from seventy-three ESRD patients. Control plasma samples (NHP) from healthy, non-smoking adults aged 19 to 53 were obtained commercially. Validated ELISA methods have been used to profile each of the biomarkers. The levels of endogenous GAGs were determined (Redprobes UG, Germany). To compare the levels of thromboinflammatory biomarkers, anti-PF4 IgG, and endogenous GAGs in different groups, appropriate statistical methods included Mann-Whitney U, t-tests, Kruskal-Wallis ANOVA and experiment correlation analysis methods were performed.
Results
All of the biomarkers and GAGs were significantly elevated, with the exception of TAFI, in ESRD patients. The ESRD patients exhibited varying levels of increase in the D-Dimer, CRP, vWF, PAI-1, anti-PF4 IgG, and GAGs as shown in Figure 1 (p < 0.05). D-Dimer showed the most pronounced increase (1075%) followed by PAI-1 (361.31%), anti-PF4 IgG (209.78%), CRP (101.77%) and endogenous GAGs (17.29%). The correlation analysis revealed varying degrees of association among these biomarkers (Figure 2).
Conclusion
These results suggest that thromboinflammatory biomarkers offer the potential utility of identifying inflammation in end-stage renal disease. Marked increase in thromboinflammatory mediators due to endothelial damage may result in the upregulation of glycosaminoglycans and anti-PF4 IgG antibodies in the ESRD patients.
En-stage renal disease (ESRD) is a growing public health problem. The atherosclerotic cardiovascular complications are the leading causes of mortality and morbidity in the ESRD. In this study, we sought to quantify the levels of thrombo-inflammatory biomarkers in an ESRD patients in comparison to healthy controls to determine their relevance in thrombo-inflammation and adverse outcomes. The levels of D-Dimer, C-reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1) antigen, functional PAI-1, thrombin activatable fibrinolysis inhibitor, tissue plasminogen activator, von Willebrand factor, and anti-PF4 IgG and microparticle (MP) activity were quantified by using commercially available ELISA immunoassays for each of the ESRD ( n = 73) and control plasma samples ( n = 10). The levels of endogenous glycosaminoglycans (GAGs) were quantified by utilizing a Heparin Red Probe (Redprobes UG, Germany). The collected data were analyzed to demonstrate the relationship between various parameters. All the tested biomarkers were increased in ESRD patients in comparison to healthy controls ( p < 0.05). These biomarkers have shown significant correlations within each other except for anti-PF4 Ig G and MPs. The CRP levels were significantly higher in patients who had coronary artery disease (CAD) ( p < 0.05), but there was no significant difference in other biomarkers according to the cardiovascular outcomes. In the multivariate analysis, the CRP (odds ratio: 1.19; 95% confidence interval: 1.01–1.41; p: 0.03) value was an independent predictor of CAD. In this study, we demonstrated increased levels of 10 different biomarkers in ESRD patients. The CRP levels can be a good predictor of CAD in ESRD patients.
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