title: 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.
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.
  
  
  CONCLUSIONS
  The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro.
authors.affiliation: Department of Nephrology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Jeong
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Ja-Yoon
authors.initials: JY
authors.lastname: Gu
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Ryu
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Kim
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D004247:DNA / Q000097:blood* / Q000737:chemistry; D005260:Female; D006657:Histones / Q000097:blood* / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy
chemical_list: D015415:Biomarkers; D006657:Histones; C508600:IL6 protein, human; D015850:Interleukin-6; D004247:DNA