Abstract
BackgroundRemote 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.MethodsKidney 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.ResultsIn 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).ConclusionsOur 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.
Highlights
Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation
Remote ischemic conditioning (RIC) has been proposed as a therapeutic modality to mitigate the effects of ischemia/reperfusion injury (IRI) in organ transplantation [4, 5]
Using samples obtained from our original porcine RIC model [18], we have studied whether we could detect any proteomic and transcriptomic changes in recipient tissue using advanced quantitative mass spectrometry and RNA sequencing
Summary
Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Acute kidney injury (AKI) induced by ischemia and subsequent reperfusion is called delayed graft function in the clinical transplant setting and leads to the need for dialysis, as well as a risk of poorer transplant outcome [3]. Remote ischemic conditioning (RIC) has been proposed as a therapeutic modality to mitigate the effects of ischemia/reperfusion injury (IRI) in organ transplantation [4, 5]. Our previous work in a porcine model of kidney transplantation suggested a beneficial effect of RIC on early graft perfusion and function evidenced by a significantly improved renal plasma perfusion and glomerular filtration rate (GFR) [18].
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