Proteomics

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PROTEOMIC ANALYSIS OF MACHINE PERFUSION SOLUTION FROM BRAIN DEAD DONOR KIDNEYS REVEALS THAT COMPLEMENT ACTIVATION IS ASSOCIATED WITH 1-YEAR OUTCOME


ABSTRACT: Current strategies to assess donor kidney quality are based on clinical scores or require biopsies for histological assessment. Non-invasive strategies to identify and predict graft outcome at an early stage are therefore needed. Our aim was to evaluate the secretome in non-oxygenated hypothermic machine perfusion (HMP) perfusate of donation after brain death (DBD) kidneys by comparing proteomic profiles of good outcome (GO) and ¬suboptimal outcome (SO) 1-year post transplantation. Samples taken 15 minutes after start of HMP (T1) and before termination of HMP (T2) were analysed using 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. Upregulated expression of proteins involved in classical complement activation at both T1 and T2, and downregulated expression lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO vs. 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. This study shows that the secretome of DBD kidneys can distinguish between outcome 1-year post transplantation. Furthermore, it provides insights into mechanisms that could play a role in post- transplant outcomes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Leonie van Leeuwen  

LAB HEAD: Prof. Benedikt Kessler

PROVIDER: PXD027127 | Pride | 2022-08-12

REPOSITORIES: Pride

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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 LL   Spraakman Nora A NA   Brat Aukje A   Huang Honglei H   Thorne Adam M AM   Bonham Sarah S   van Balkom Bas W M BWM   Ploeg Rutger J RJ   Kessler Benedikt M BM   Leuvenink Henri G D HGD  

Transplant international : official journal of the European Society for Organ Transplantation 20210901 9


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 af  ...[more]

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