Proteomic analysis of machine perfusion solution from brain dead donor kidneys reveals that elevated complement, cytoskeleton and lipid metabolism proteins are associated with 1-year outcome

L Leonie van Leeuwen, Nora A Spraakman, Aukje Brat, Honglei Huang, Adam M Thorne, Sarah Bonham, Bas W M van Balkom, Rutger J Ploeg, Benedikt M Kessler, Henri G D Leuvenink

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Abstract

Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1-year post-transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP-citrate synthase and fatty acid-binding protein 5 (T1) and immunoglobulin heavy variable 2-26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1-year post-transplantation. Furthermore, it provides insights into mechanisms that could play a role in post-transplant outcomes.

Original languageEnglish
Pages (from-to)1618-1629
Number of pages12
JournalTransplant International
Volume34
Issue number9
DOIs
Publication statusPublished - Sep-2021

Keywords

  • biomarker discovery
  • complement activation
  • donation after brain death
  • hypothermic machine perfusion
  • kidney preservation
  • proteomics
  • DELAYED GRAFT FUNCTION
  • EXPANDED CRITERIA DONORS
  • COLD-STORAGE
  • COMPUTATIONAL PLATFORM
  • RENAL-TRANSPLANTATION
  • C4B-BINDING PROTEIN
  • PRESERVATION
  • INHIBITOR
  • STANDARD
  • RECIPIENTS

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