title: The effect of renal dysfunction and haemodialysis on circulating liver specific miR-122.
abstract: microRNA-122 (miR-122) is a hepatotoxicity biomarker with utility in the management of paracetamol overdose and in drug development. Renal dysfunction and haemodialysis have been associated with a reduction in circulating microRNA. The objective of this study was to determine their effect on miR-122.
  
  
  
  Blood samples were collected from 17 patients with end-stage renal disease (ESRD) on haemodialysis, 22 healthy controls, 30 patients with chronic kidney disease (CKD) and 15 patients post-kidney transplantation. All had normal standard liver function tests. Samples from ESRD patients were collected immediately pre- and post-haemodialysis. Serum alanine transaminase activity (ALT), miR-122 and miR-885 (liver enriched) were compared.
  
  
  
  Circulating miR-122 was substantially reduced in ESRD patients pre-haemodialysis compared with the other groups (19.0-fold lower than healthy controls; 21.7-fold lower than CKD). Haemodialysis increased miR-122 from a median value of 6.7 × 103(2.3 × 103-1.4 × 104) to 1.6 × 104(5.4 × 103-3.2 × 104) copies ml-1. The increase in miR-122 did not correlate with dialysis adequacy. miR-122 was reduced in the argonaute 2 bound fraction pre-haemodialysis; this fraction was increased post-dialysis. There was no change in miR-122 associated with extracellular vesicles. miR-885 was also reduced in ESRD patients (4-fold compared to healthy subjects) and increased by haemodialysis.
  
  
  
  miR-122 is substantially lower in ESRD compared to healthy controls, patients with CKD and transplanted patients. Haemodialysis increases the concentration of miR-122. These data need to be considered when interpreting liver injury using miR-122 in patients with ESRD on dialysis, and specific reference ranges that define normal in this setting may need to be developed.
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Laura
authors.initials: L
authors.lastname: Rivoli
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: A D Bastiaan
authors.initials: AD
authors.lastname: Vliegenthart
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Carmelita M J
authors.initials: CM
authors.lastname: de Potter
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Job J M H
authors.initials: JJ
authors.lastname: van Bragt
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tzoumas
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Peter
authors.initials: P
authors.lastname: Gallacher
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Tariq E
authors.initials: TE
authors.lastname: Farrah
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhaun
authors.affiliation: Edinburgh University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh.
authors.forename: James W
authors.initials: JW
authors.lastname: Dear
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D006435:Renal Dialysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; C574934:MIRN885 microRNA, human; D035683:MicroRNAs; D000410:Alanine Transaminase
keywords: chronic kidney disease; dialysis; hepatotoxicity; miR-122; microRNA