Introduction and Aims: End-Stage Renal Disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid clinical outcomes. The relevance of some of the biomarkers of inflammation and metabolic syndrome to vascular outcomes in ESRD is not clear. In order to study these relationships, biochip array technology offers a method to profile the complex plasma biomarker environment in the setting of various comorbid clinical outcomes such as Stroke or Transient Ischemic Attack (TIA), Acute Coronary Syndrome (ACS), Congestive Heart Failure (CHF), and Coronary Artery Disease (CAD).

Methods: Plasma samples were collected from 83 ESRD patients (mean age 65) prior to hemodialysis and were profiled using biochips for metabolic and inflammatory biomarker levels. Inflammatory cytokine and Metabolic Syndrome arrays (RANDOX, Antrim, UK) were used to profile C peptide, ferritin, insulin, leptin, resistin, TNFa, PAI-1, IL1a, IL1b, IL2, IL4, IL6, IL8, IL10, VEGF, EGF, IFNG, and MCP1. Retrospective review of the medical record was performed in order to group patients based on history of Stroke or TIA, ACS, CHF, and CAD. Plasma biomarker levels were then compared between groups with and without history of each comorbidity.

Results: Of the 83 ESRD patients, 25 (30.1%) were found to have history of Stroke/TIA, 14 (16.9%) were found to have history of ACS, 30 (36.1%) were found to have history of CHF, and 39 (47.0%) were found to have history of CAD. The patients with history of Stroke/TIA were found to have decreased plasma IFNG levels (p=0.042) and elevated plasma resistin, IL1a, and leptin levels (p=0.008, 0.021, 0.026; respectively) when compared to ESRD patients without history of Stroke/TIA. The patients with history of ACS were found to have elevated plasma IL6 levels (p=0.040) when compared to ESRD patients without history of ACS. The patients with history of CHF were found to have decreased plasma leptin levels (p=0.031) and elevated plasma IL1b levels (p=0.042) when compared to ESRD patients without history of CHF. The patients with history of CAD were found to have elevated plasma IL1a levels (p=0.049) when compared to ESRD patients without history of CAD.

Conclusions: Profiling of multiple inflammatory and metabolic syndrome biomarkers may aid in the risk stratification of ESRD patients for cerebrovascular and cardiovascular disorders. IL1a was found to be elevated in both Stroke/TIA and CAD, whereas in Stroke, resistin, and leptin were also higher along with decreased IFNG. Interestingly, despite an increase in IL1b, leptin was decreased in CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.

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