title: Presence of Cytotoxic Extracellular Histones in Machine Perfusate of Donation After Circulatory Death Kidneys.
abstract: Extracellular histones are cytotoxic molecules that are related to cell stress and death. They have been shown to play a crucial role in multiple pathophysiologic processes like sepsis, inflammation, vascular dysfunction, and thrombosis. Their role in organ donation and graft function and survival is still unknown. The aim of this study was to assess whether an association exists between the presence of extracellular histones in machine perfusates and deceased donor kidney viability.
  
  
  
  Machine perfusates of 390 donations after circulatory death kidneys were analyzed for histone concentration, and corresponding graft function and survival were assessed.
  
  
  
  Extracellular histone concentrations were significantly higher in perfusates of kidneys with posttransplant graft dysfunction (primary nonfunction and delayed graft function) and were an independent risk factor for delayed graft function (odds ratio, 2.152; 95% confidence interval [95% CI], 1.199-3.863) and 1 year graft failure (hazard ratio, 1.386; 95% CI, 1.037-1.853), but not for primary nonfunction (odds ratio, 1.342; 95% CI, 0.900-2.002). One year graft survival was 12% higher in the group with low histone concentrations (P = 0.008) as compared with the group that contained higher histone concentrations.
  
  
  
  This study warrants future studies to probe for a possible role of cytotoxic extracellular histones in organ viability and suggests that quantitation of extracellular histones might contribute to assessment of posttransplant graft function and survival.
authors.affiliation: 1 Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. 2 Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands. 3 Department of Methodology and Statistics, School for Public Health and Primary Care (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands. 4 Department of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands. 5 Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tim C
authors.initials: TC
authors.lastname: van Smaalen
authors.forename: Daniëlle M H
authors.initials: DM
authors.lastname: Beurskens
authors.forename: E R Pieter
authors.initials: ER
authors.lastname: Hoogland
authors.forename: Bjorn
authors.initials: B
authors.lastname: Winkens
authors.forename: Maarten H L
authors.initials: MH
authors.lastname: Christiaans
authors.forename: Chris P
authors.initials: CP
authors.lastname: Reutelingsperger
authors.forename: L W Ernest
authors.initials: LW
authors.lastname: van Heurn
authors.forename: Gerry A F
authors.initials: GA
authors.lastname: Nicolaes
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002423:Cause of Death; D051799:Delayed Graft Function / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006085:Graft Survival; D006657:Histones / Q000009:adverse effects / Q000032:analysis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D019188:Organ Preservation Solutions / Q000737:chemistry*; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D055031:Primary Graft Dysfunction / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D014022:Tissue Survival; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006657:Histones; D019188:Organ Preservation Solutions