Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation

Blood Purif. 2016;41(1-3):64-71. doi: 10.1159/000440974. Epub 2015 Oct 31.

Abstract

Background: Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients.

Methods: The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro.

Results: Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro.

Conclusion: The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / pathology
  • Case-Control Studies
  • DNA / blood*
  • DNA / chemistry
  • Female
  • Histones / blood*
  • Histones / chemistry
  • Humans
  • Interleukin-6 / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neutrophil Activation
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Prognosis
  • Prospective Studies
  • Renal Dialysis*
  • Uremia / blood*
  • Uremia / complications
  • Uremia / pathology
  • Uremia / therapy

Substances

  • Biomarkers
  • Histones
  • IL6 protein, human
  • Interleukin-6
  • DNA