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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

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 nonoxy...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292651/
https://www.ncbi.nlm.nih.gov/pubmed/34448265
http://dx.doi.org/10.1111/tri.13984
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author 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.
author_facet 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.
author_sort van Leeuwen, L. Leonie
collection PubMed
description 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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spelling pubmed-92926512022-07-20 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. Transpl Int Original Articles 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. John Wiley and Sons Inc. 2021-08-26 2021-09 /pmc/articles/PMC9292651/ /pubmed/34448265 http://dx.doi.org/10.1111/tri.13984 Text en © 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
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.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292651/
https://www.ncbi.nlm.nih.gov/pubmed/34448265
http://dx.doi.org/10.1111/tri.13984
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