title: Nucleosome levels and toll-like receptor expression during high cut-off haemofiltration: a pilot assessment.
abstract: OBJECTIVE
  To measure plasma nucleosome levels and expression of toll-like receptors (TLRs) in a pilot cohort of patients with severe acute kidney injury (AKI) within a randomised controlled trial of continuous venovenous haemofiltration with high cut-off filters (CVVH-HCO) v standard filters (CVVH-std).
  
  
  METHODS
  We measured plasma nucleosome levels using the Cell Death Detection ELISA PLUS (10X) assay kit. We analysed plasma levels for correlation with disease severity and compared the effects of CVVH-HCO and CVVH-std on plasma nucleosome levels over the first 72 hours. We studied cell surface TLR expression on CD14-positive monocytes in a subcohort of CVVH-HCO patients.
  
  
  RESULTS
  We did not detect nucleosomes in normal human plasma, but found elevated nucleosome levels in patients with severe AKI. Nucleosome levels at randomisation correlated weakly with Acute Physiology and Chronic Health Evaluation III scores (Pearson ρ=0.475, P=0.016). Treatment with CVVH-HCO or CVVH-std had no effect on nucleosome levels over 72 hours. The mean fluorescence intensity (MFI) ratios of TLR2 and TLR4 expression were elevated throughout the 72-hour period (range for TLR2, 0.97-3.98; range for TLR4, 0.91-10.18) and did not appear to decrease as a result of treatment with CVVH-HCO.
  
  
  CONCLUSIONS
  Nucleosome concentration was elevated in the plasma of patients with severe AKI and mildly correlated with disease severity, but was not affected by treatment with CVVH-HCO or CVVH-std. Similarly, levels of TLR2 and TLR4 expression did not decrease over time during CVVHCrit HCO treatment.
authors.affiliation: Johor Bahru Clinical School, Monash University Malaysia, Johor, Malaysia. rinaldo.bellomo@austin.org.au.
authors.forename: Rafidah
authors.initials: R
authors.lastname: Atan
authors.affiliation: Howard Florey Institute, Univerisity of Melbourne, Melbourne, VIC, Australia.
authors.forename: Clive
authors.initials: C
authors.lastname: May
authors.affiliation: Faculty of Veterinary Science, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
authors.affiliation: Sirtex Medical Ltd, Sydney, NSW, Australia.
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanudji
authors.affiliation: Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Kumar
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Narelle
authors.initials: N
authors.lastname: Skinner
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Melbourne, VIC, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.
authors.forename: Hermann
authors.initials: H
authors.lastname: Goehl
authors.affiliation: Gambro Dialysatoren GmbH, Research and Development, Hechingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Storr
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000150:complications / Q000628:therapy*; D000368:Aged; D015331:Cohort Studies; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006440:Hemofiltration / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism*; D010865:Pilot Projects; D006435:Renal Dialysis; D012720:Severity of Illness Index; D051193:Toll-Like Receptors / Q000097:blood*
chemical_list: D009707:Nucleosomes; D051193:Toll-Like Receptors