PB0032 - Interpaly of Oxidative Stress Markers with Thrombo-Inflammatory Barkers in End Stage Renal Disease.

Background: End stage renal disease (ESRD) represent a complex pathophysiologic syndrome which results in endothelial dysfunction, hemostatic dysregulation, and hemodynamic complications. Cellular dysfunction and metabolic changes results in the generation of various biomarkers which can be measured in the plasma of ESRD patients.

Aims: Since, oxidative stress and thrombo-inflammatory processes contribute to the pathogenesis of this syndrome, this sought to measure some of the markers related to these processes in the ESRD patients.

Methods: Seventy-eight patients with ESRD undergoing maintenance hemodialysis were enrolled in the study under an IRB approved protocol. Normal human plasma (NHP) was used as control. Plasma samples were analyzed for biomarker of oxidative stress; myeloperoxidase (MPO), malondialdehyde (MDA), nitrotyrosine, endothelial NO synthase (eNOS), and nitric oxide (NO) and thrombi-inflammatory biomarkers; D-Dimer, PAI-1, tPA, TAFI, vWF, & CRP. Applicable statistical analysis was performed by using GraphPad Prism Software.

Results: ESRD patients showed upregulation of most of the markers, MPO (1.06-fold), MDA (1.30-fold), nitrotyrosine (2.31-fold), eNOS (0.83-fold), NO (2.51-fold), D-Dimer (25.38), PAI-1 antigen (1.37-fold), tPA (1.36-fold), TAFIa (1.20-fold), vWF (2.04-fold), and CRP (8.04-fold) increase compared to NHP. Varying levels of positive and negative correlations were noted between oxidative stress markers and thrombi-inflammatory markers (figure 1). MPO was positively correlated with TAFI (r=0.32) and CRP (r=0.25), MDA was positively correlated with nitrotyrosine (r=0.46), nitrotyrosine was positively correlated with vWF (r=0.23), and NO was negatively correlated with PAI-1 (r=-0.28).

Conclusion(s): These studies suggest that profiling of thrombo-inflammatory and oxidative stress markers may be helpful in the understanding of the pathogenesis of ESRD. Both group of biomarkers are upregulated in ESRD group in comparison to normal cohort. Moreover, the oxidative stress biomarker shows varying degrees of correlation with thrombo-inflammatory biomarkers suggesting an interplay between these pathophysiologic processes.