Subclinical effects of remote ischaemic conditioning in human kidney transplants revealed by quantitative proteomics

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  • Adam M. Thorne, University of Oxford
  • ,
  • Honglei Huang, University of Oxford
  • ,
  • Darragh P. O‘Brien, University of Oxford
  • ,
  • Marco Eijken
  • Nicoline Valentina Krogstrup
  • ,
  • Rikke Norregaard
  • Bjarne Møller
  • Rutger J. Ploeg, University of Oxford
  • ,
  • Bente Jespersen
  • Benedikt M. Kessler, University of Oxford

Background: Remote ischaemic conditioning (RIC) is currently being explored as a non-invasive method to attenuate ischaemia/reperfusion injuries in organs. A randomised clinical study (CONTEXT) evaluated the effects of RIC compared to non-RIC controls in human kidney transplants. Methods: RIC was induced prior to kidney reperfusion by episodes of obstruction to arterial flow in the leg opposite the transplant using a tourniquet (4 × 5 min). Although RIC did not lead to clinical improvement of transplant outcomes, we explored whether RIC induced molecular changes through precision analysis of CONTEXT recipient plasma and kidney tissue samples by high-resolution tandem mass spectrometry (MS/MS). Results: We observed an accumulation of muscle derived proteins and altered amino acid metabolism in kidney tissue proteomes, likely provoked by RIC, which was not reflected in plasma. In addition, MS/MS analysis demonstrated transient upregulation of several acute phase response proteins (SAA1, SAA2, CRP) in plasma, 1 and 5 days post-transplant in RIC and non-RIC conditions with a variable effect on the magnitude of acute inflammation. Conclusions: Together, our results indicate sub-clinical systemic and organ-localised effects of RIC.

Original languageEnglish
Article number39
JournalClinical Proteomics
Volume17
Issue1
Number of pages13
ISSN1542-6416
DOIs
Publication statusPublished - Nov 2020

    Research areas

  • Acute phase proteins, CONTEXT clinical trial, ELISA, Kidney transplantation, Mass spectrometry, Proteomics, Remote ischaemic conditioning

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