Increase of high mobility group box 1 protein levels (HMGB1) in patients with chronic kidney disease (CKD) after hemodialysis

Abstract

1.1 Background: There are few studies on approaching the blood level of inflammatory mediators in Chronic Kidney Disease (CKD) patients before and after hemodialysis.

1.2  Objective: With the aim of establishing the inflammatory profile in patients with CKD, we have determined the levels of thrombomodulin (TM) (anticoagulant and  anti-inflammatory), high mobility group box 1 protein (HMGB1), IL-1β and IL-6 (proinflammatory cytokines), and MDA (malondialdehyde), a biomarker for oxidative stress,  in a descriptive paired study in CKD patients before and after hemodialysis.

1.3 Methods: The study population comprised twenty patients with CKD, each of whom had been undergoing hemodialysis treatment for approximately seven years. Levels of HMGB1, TM, IL-1β, IL-6 and MDA were determined by enzyme-linked immunosorbent assay of blood samples collected from each patient before and after hemodialysis.  

1.4 Results: Mean values of HMGB1 increased substantially from 0.48±0.2 to 1.07±0.5ng/mL (p<0.05) following hemodialysis, while mean levels of TM showed only a minor increase from 9.01±0.9 to 9.35±0.9 ng/mL (p>0.05). The median of IL-6 and IL-1β, expressed as pg/mL, were 15.3 (8.8-40.7) to 16.10 (9.5–51) (p>0.05) and 10.3 (5.3–32.3) to 9.7 (5.3–34.2), before and after hemodialysis, respectively. The HMGB1/TM ratio rose by a factor of 2.86 following hemodialysis. No correlations were detected between HMGB-1 and TM, IL-6, IL-1β or MDA levels before or after hemodialysis. Blood urea levels decreased significantly after hemodialysis, as expected.

1.5 Discussion: Hemodialysis decreases toxic components (e.g. urea) in blood but induces a significant increase in HMGB-1 without affecting other proinflammatory biomarkers. The observed increase in HMGB1 concentration could be due to interaction between blood cells and the filter membrane leading to cellular death without consequent releasing of pro-inflammatory cytokines and activation of innate immunity, evaluated by IL-1β and IL-6 neither biomarker for oxidative stress (MDA). Hemodialysis did not induce or aggravated inflammatory profile of CKD patients.