Thrombo-inflammatory Biomarkers in Patients with End-Stage Renal Disease

INTRODUCTION: End-stage renal disease (ESRD) the final stage of chronic kidney disease is a life-threatening condition in which an individual's kidneys completely cease function, and dialysis or a kidney transplant is required for the individual to survive. In the United States, the most common causes of ESRD are high blood pressure and diabetes, as these conditions can cause damage to one's kidneys. ESRD can also lead to an individual developing a state of inflammation, such as atherosclerosis. Interleukin (IL) 6 is a mediator of acute inflammation and fever that stimulates the autoimmune and inflammatory process in several diseases, such as atherosclerosis. Tumor necrosis factor alpha (TNF-α) is an inflammatory molecule produced during acute inflammation. D-dimer is a fibrin degradation product, and the estimation of its concentration can be used to help diagnose thrombosis. PURPOSE: The purpose of this research project was to analyze concentrations of thrombo-inflammatory biomarkers in ESRD patients compared to the general population, and their role in the development of ESRD. HYPOTHESIS: It is hypothesized that circulating levels of thrombo-inflammatory biomarkers of kidney disfunction may be elevated in ESRD patients. MATERIALS AND METHODS: This study was conducted using plasma samples from 95 ESRD patients. The samples were centrifuged to produce platelet poor plasma, aliquoted, and frozen at -80 degrees Celsius. Sandwich ELISA kits were used to measure levels of D-dimer, IL-6, and TNF-α in the ESRD patients' blood plasma samples. 50 samples of normal human plasma (NHP), commercially obtained from a centralized blood bank, served as a control group for comparison. STATISTICAL ANALYSIS: Statistical analyses were conducted to determine statistical significance of the data and to identify any correlation between the biomarkers. Tests for normal distribution, t-tests, Mann-Whitney tests, skewness tests, quartile analysis, and correlation analysis were conducted using PRISM GraphPad and IBM Statistical Package for the Social Sciences (SPSS) software to analyze the data. The p-values were compared to the α-level of 0.05 to determine statistical significance. RESULTS: The results were compiled as Mean ± Standard Error of the Mean (SEM). D-dimer, IL-6, and TNF-α showed statistically significantly higher concentrations in ESRD patient blood plasma (ESRD 1447.01 ± 215.79 ng/mL vs. 187.73 ± 30.05 ng/mL, p-value < 0.0001), (ESRD 5.21 ± 1.46 pg/mL vs. 1.25 ± 0.18 pg/mL, p-value < 0.0001), and (ESRD 2.515 ± 0.15 pg/mL vs. 1.73 ± 0.15 pg/mL, p-value = 0.0006), respectively. Additionally, a low, positive correlation was reported among each of the biomarkers. Thus, subjects with ESRD had higher levels of D-dimer, IL-6, and TNF-α, likely due to these biomarkers' relation to inflammation and kidney dysfunction. CONCLUSION: These studies suggest that the levels of thrombo-inflammatory biomarkers (D-dimer, IL-6, and TNF-α) in ESRD patients show statistically significant elevation. These results provide a pathway towards the potential future diagnosis of patients with ESRD using thrombo-inflammatory biomarkers. © FASEB.