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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.
van Leeuwen, L Leonie; Spraakman, Nora A; Brat, Aukje; Huang, Honglei; Thorne, Adam M; Bonham, Sarah; van Balkom, Bas W M; Ploeg, Rutger J; Kessler, Benedikt M; Leuvenink, Henri G D.
Afiliación
  • van Leeuwen LL; Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Spraakman NA; Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Brat A; Department of Anaesthesiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Huang H; Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Thorne AM; Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Bonham S; Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • van Balkom BWM; Nuffield Department of Surgical Sciences, University of Oxford, BRC Oxford and NHS Blood and Transplant, Oxford, UK.
  • Ploeg RJ; Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
  • Kessler BM; Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Leuvenink HGD; Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
Transpl Int ; 34(9): 1618-1629, 2021 Sep.
Article en En | MEDLINE | ID: mdl-34448265
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Muerte Encefálica / Trasplante de Riñón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transpl Int Asunto de la revista: TRANSPLANTE Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Muerte Encefálica / Trasplante de Riñón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transpl Int Asunto de la revista: TRANSPLANTE Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza