Presence of Cytotoxic Extracellular Histones in Machine Perfusate of Donation after Circulatory Death Kidneys.

Background: 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. Methods: Machine perfusates of 390 donation after circulatory death kidneys were analysed for histone concentration and corresponding graft function and survival were assessed. Results: Extracellular histone concentrations were significantly higher in perfusates of kidneys with posttransplant graft dysfunction (primary non function (PNF) and delayed graft function (DGF)) and were an independent risk factor for DGF (OR=2.152 (1.199-3.863)) and one year graft failure (HR=1.386 (1.037-1.853)), but not for PNF (OR=1.342 (0.900-2.002). One year graft survival was 12% higher in the group with low histone concentrations (p=.008) as compared to the group that contained higher histone concentrations. Conclusions: 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. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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