Elevated extracellular nucleosomes and their relevance to inflammation in stage 5 chronic kidney disease.

BACKGROUND: Chronic kidney disease is a disorder characterized by a pro-inflammatory state that is associated with increased morbidity and mortality. Endogenous damage-associated molecular patterns, including nucleosomes, may contribute to this persistent inflammation. The aim of this study was to profile and evaluate the clinical significance of circulating nucleosomes in patients with Stage 5 chronic kidney disease (CKD5) on hemodialysis (HD). METHODS: Under institutional review board approval, plasma samples were collected from 90 CKD5-HD patients (45 male and 45 female) prior to hemodialysis. Normal human plasma samples (25 male and 25 female) were used as a control group. Commercial enzyme-linked immunosorbent and colorimetric assays were used to profile nucleosome levels and biochemical markers of kidney injury, inflammation, thrombosis, and renal function in CKD5-HD and control groups. Clinical laboratory parameters were documented from the electronical medical record and correlated to nucleosome levels in the CKD5-HD cohort. RESULTS: In comparison to healthy volunteers, the plasma from CKD5-HD patients exhibited markedly elevated nucleosomes (P<0.0001). Furthermore, nucleosome levels correlated with WBC count (P=0.025, R=0.243) and CRP (P=0.019, R=0.266) levels. No correlation was found between nucleosomes and the other parameters studied. CONCLUSIONS: Our findings indicate extracellular nucleosomes are significantly elevated in CKD5-HD, suggesting increased cell death and/or inflammation. The observed correlations between nucleosomes and parameters of inflammation is suggestive of a complex, systemic inflammatory process underlying renal deterioration, consistent with the literature. Thus, nucleosomes may play a role in the pathogenesis and outcome of CKD5-HD.