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

TY - JOUR

T1 - Subclinical effects of remote ischaemic conditioning in human kidney transplants revealed by quantitative proteomics

AU - Thorne, Adam M.

AU - Huang, Honglei

AU - O‘Brien, Darragh P.

AU - Eijken, Marco

AU - Krogstrup, Nicoline Valentina

AU - Norregaard, Rikke

AU - Møller, Bjarne

AU - Ploeg, Rutger J.

AU - Jespersen, Bente

AU - Kessler, Benedikt M.

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - Acute phase proteins

KW - CONTEXT clinical trial

KW - ELISA

KW - Kidney transplantation

KW - Mass spectrometry

KW - Proteomics

KW - Remote ischaemic conditioning

UR - http://www.scopus.com/inward/record.url?scp=85094896785&partnerID=8YFLogxK

U2 - 10.1186/s12014-020-09301-x

DO - 10.1186/s12014-020-09301-x

M3 - Journal article

C2 - 33292164

AN - SCOPUS:85094896785

SN - 1542-6416

VL - 17

JO - Clinical Proteomics

JF - Clinical Proteomics

IS - 1

M1 - 39

ER -