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Updated: Oct 3, 2025
Orthotopic Kidney Auto-Transplantation in a Porcine Model Using 24 Hours Organ Preservation And Continuous Telemetry
Published on: August 21, 2020
Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney
Darragh P O'Brien1, Adam M Thorne2,3, Honglei Huang2,3
1Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK. darragh.obrien@ndm.ox.ac.uk.
Background:
Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls.
Methods:
Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed an integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC.
Results:
In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. However, the majority of these protein changes did not reach significance (p < 0.05).
Conclusions:
Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation.
Insights
Remote Ischemic Conditioning (RIC) minimally altered kidney transplant molecular profiles in pigs, showing suppressed inflammation but no significant protein changes. This research aids in optimizing RIC protocols for renal transplantation.
Area of Science:
- Transplantation immunology
- Organ preservation strategies
- Molecular biology
Background:
- Remote Ischemic Conditioning (RIC) is a potential therapy to mitigate ischemia/reperfusion injury (IRI) in organ transplantation.
- Understanding the subclinical molecular effects of RIC is crucial for its clinical application.
Purpose of the Study:
- To investigate the molecular impact of RIC on kidney grafts in a porcine model.
- To compare molecular signatures in RIC-treated versus non-RIC control kidney grafts.
Main Methods:
- Utilized a porcine kidney transplant model with 8 pairs of kidneys.
- Applied an integrated Omics approach (transcriptomics, proteomics, phosphoproteomics).
- Assessed molecular changes 10 hours post-transplantation.
Main Results:
- Minimal transcriptomic and proteomic perturbations were observed in RIC-treated kidneys compared to controls.
- RIC led to suppressed inflammatory profiles in kidney tissues.
- An accumulation of extracellular matrix proteins was noted, potentially linked to muscle damage, though not statistically significant.
Conclusions:
- RIC induces subtle molecular phenotypes in porcine kidneys.
- Findings may inform the optimization of RIC protocols for renal transplantation.
