Interleukin-8 Is a Powerful Prognostic Predictor of All-Cause and Cardiovascular Mortality in Dialytic Patients

Abstract

Background: Cohort studies have demonstrated an association between C-reactive protein (CRP) and interleukin-6 (IL-6) and all-cause and cardiovascular mortality in end-stage renal disease (ESRD) patients. Interleukin-8 (IL-8) appears to be not only the plasma expression of the acute-phase response but also a direct pathogenetic mediator of the atherosclerotic process. Methods: To evaluate the role of IL-8 in predicting outcome, 76 chronic dialytic patients were prospectively followed for 18 months. At baseline, blood samples were taken for analysis of high-sensitivity CRP, IL-6, IL-8 and other standard laboratory analyses. Results: Median IL-8 was 5.2 mg/l, therefore near half of the patients had IL-8 values within the range of ‘normal limits’. IL-6 and CRP were significantly correlated (r = 0.45, p < 0.001) and a positive correlation was also found between IL-6 and IL-8 (r = 0.39, p < 0.001). The correlation coefficient between IL-6 and CRP was 0.43 (p < 0.001) and 0.50 (p < 0.001) in patients without and with history and/or clinical signs of cardiovascular disease, respectively. After a follow-up of 1.5 years, 8 patients had died from cardiovascular causes and another 7 patients for other reasons; furthermore 9 major nonfatal cardiovascular events were recorded. Stepwise regression analysis showed IL-8 as the strongest independent predictor of all-cause and cardiovascular events (p = 0.0025) even after adjustment for age and dialytic age, followed by IL-6 and CRP (p < 0.01). Conclusion: Despite a small population and a relatively short follow-up period, this study firstly demonstrated that IL-8 is a powerful independent predictive factor for cardiovascular and overall mortality cause in ESRD patients.

Increased Plasma and Endothelial Cell Expression of Chemokines and Adhesion Molecules in Chronic Kidney Disease

“…This may be due to the known sources of IL-8 production, which are mainly linked to cells other than the endothelial cells. Moreover, the paradoxical associations between in vitro and in vivo findings as well as between IL-8, FMD and IMT contrast with previous studies and deserve further investigation [29]. …”

Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin‐8 (CXCL8), Myeloid‐Related Protein 8/Myeloid‐Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease

“…In addition, many non-gout-focused studies showed a role for CXCL8 in predicting CVD. CXCL8 functions as an independent predictor for clinical outcome in patients with coronary artery disease (34) and for CVD in patients with end-stage renal disease (35). Finally, CXCL8 was found to be increased in diabetes mellitus and was suggested to be a marker linking obesity with metabolic complications such as atherosclerosis and diabetes mellitus (11).…”

Cholecalciferol Supplementation Alters Calcitriol-Responsive Monocyte Proteins and Decreases Inflammatory Cytokines in ESRD

“…Alterations in monocytes and monocyte-derived cytokines have been implicated in the inflammatory pathology that exists in ESRD. 39,41,44,48,49 IL-8, IL-6, and TNF-␣ are possible direct mediators in the pathogenesis of atherosclerosis. 50 -58 In addition, there seems to be a significant correlation between the level of these various cytokines and patient outcomes, with multiple studies suggesting that elevations in IL-8, IL-6, and TNF-␣ levels are associated with increased morbidity and mortality in patients with ESRD.…”