Upregulation of Inflammatory Mediators In End-Stage Renal Disease as Measured Via Biochip Array Technology

Abstract 5186

End-Stage Renal Disease (ESRD) is a complex syndrome in which systemic vascular pathophysiologic changes contribute to adverse cardiovascular and cerebrovascular manifestations. Cardiovascular disease alone is present in over 60% of patients with ESRD and contributes heavily to mortality among this population. Given that inflammatory and hemostatic aberrations contribute to the overall pathogenesis of the syndrome, the purpose of this study is to profile several inflammatory mediators in order to better understand their role in the underlying mechanism of vascular changes in ESRD. Plasma samples from 49 patients with ESRD were collected prior to maintenance hemodialysis sessions. A group of 56 normal individuals, both male and female, was included as control. Cerebral Array II chips were used in the Randox® system to simultaneously measure Neuron Specific Enolase (NSE), Neutrophil Gelatinase-associated Lipocalin (NGAL), Soluble Tumor Necrosis Factor Receptor I (TNFRI), D-Dimer (DD), Thrombomodulin (TM), and C-reactive protein (CRP). The Randox® Evidence Investigator™ is a new biochip array technology that utilizes multiple discrete test regions of immobilized antibody to simultaneously quantify multiple markers from a single patient plasma sample based on the light signal generated from each test region. The data was statistically analyzed using the Mann-Whitney U test (two-tailed with Gaussian approximation). As compared to the normal individual, all of the markers studied showed an upregulation in patients with ESRD. Most notably, TNFRI showed a 19.8 fold increase in patients with ESRD (mean 7.8 ± 2.8 ng/ml, range 0.8 to 13.7) compared to the control (mean 0.4 ± 0.2, range 0.1 to 1.0). TM was increased 5.2 fold (mean 6.5 ± 2.6, range 0.7 to 14.1) compared to control (mean 1.2 ± 0.4, range 0.6 to 2.3). Also, NGAL showed a 4.6 fold increase (mean 1390 ± 257, range 406 to 1729), compared to control (mean 299 ± 99, range 115 to 603), and CRP a 4.2 fold increase (mean 5.7 ± 4.2 ug/ml, range 0.6 to 13.2) compared to control (mean 1.4 ± 1.7, range 0.2 to 11.4). DD and NSE were also increased 3.0 and 1.8 fold respectively. These studies show that some newer markers such as TNFRI, NGAL and NSE are upregulated in ESRD. The marked increase in TM is highly suggestive of endothelial damage. Similarly, the increase in TNFRI supports a state of increased cellular damage. The elevations in NGAL and CRP imply a state of increased inflammation and indicate a polypathologic process, which may predispose ESRD patients to both cardiovascular and cerebrovascular thromboembolic events. Finally, this study further validates the role of endothelial damage and endogenous thrombotic processes in ESRD as evidenced by the increased levels of TM and DD. However, the clinical significance of these markers still needs to be further explored.