PB1209 - Thrombo-inflammatory and Fibrinolytic Deficit Biomarkers and their Relationship with Circulating Glycosaminoglycans in End-Stage Renal Disease Patients

Background: Chronic kidney disease (CKD) and terminal stage end-stage renal disease (ESRD) are growing public health problems. The atherosclerotic cardiovascular complications including myocardial infarction, stroke, and peripheral arterial disease are the leading causes of mortality and morbidity in ESRD. Understanding the relevance of thrombo-inflammatory biomarkers may provide insight into the pathophysiology of CKD and ESRD and may be useful for development of prognostic, diagnostic, and therapeutic interventions.

Aims: In this study, we sought to quantify the levels of thrombo-inflammatory and fibrinolytic deficit biomarkers in a group of ESRD patients in comparison to healthy controls to determine their relevance in thrombo-inflammation and adverse outcomes.

Methods: The levels of D-Dimer, CRP, PAI-1 antigen, functional PAI-1, TAFI, tPA, vWF, anti-PF4 IgG and microparticle 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 Heparin Red Probe (Redprobes UG, Germany). Appropriate statistical methods performed included Mann-Whitney U, t-tests, Kruskal-Wallis ANOVA, and experiment correlation analysis methods.

Results: As shown in Figure-1, the levels of all the tested biomarkers were elevated in ESRD patients in comparison to healthy controls (p < 0.05). These biomarkers have shown significant correlations within each other except anti-PF4 IgG and microparticles, as depicted in Figure-2. The CRP levels were significantly higher in patients who had coronary artery disease (CAD), (p < 0.05) but there was no significant difference in any of the other biomarkers according to the vascular complications such as cerebrovascular or peripheral artery disease.

Conclusion(s): These studies demonstrate that thrombo-inflammatory biomarkers and circulating endogenous GAGs are upregulated in ESRD patients owing to the pathophysiologic imbalances in the cellular and molecular processes. Moreover, this data is also suggestive of fibrinolytic deficit in the ESRD patients which may contribute to hemostatic dysregulation leading to vascular complications.