Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: a preclinical study
Stone, John P Amin, Kavit R Geraghty, Abbey Kerr, Jak Shaw, Matthew Dabare, Dilan Wong, Jason K Brough, David Entwistle, Timothy R Montero-Fernandez, Angeles
Stone, John P
Amin, Kavit R
Geraghty, Abbey
Kerr, Jak
Shaw, Matthew
Dabare, Dilan
Wong, Jason K
Brough, David
Entwistle, Timothy R
Montero-Fernandez, Angeles
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Affiliation
The Ex-Vivo Research Centre; University of Manchester; Manchester University NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust
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Publication date
2021-11-26
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Abstract
Introduction: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model.
Methods: Ten paired pig forelimbs were used for this study, grouped as either limb-only (LO, n = 5) perfusion, or limb-kidney (LK, n = 5) perfusion. Infrared thermal imaging was used to determine homogeneity of perfusion. Lactate, bicarbonate, base, pH, and electrolytes, along with an inflammatory profile generated via the quantification of cytokines and cell-free DNA in the perfusate were recorded.
Results: The addition of a kidney to a limb perfusion circuit resulted in the rapid stabilization of lactate, bicarbonate, base, and pH. Conversely, the LO circuit became progressively acidotic, correlating in a significant increase in pro-inflammatory cytokines. Global perfusion across the limb was more homogenous with LK compared to LO.
Conclusion: The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis.
Citation
Stone JP, Amin KR, Geraghty A, Kerr J, Shaw M, Dabare D, Wong JK, Brough D, Entwistle TR, Montero-Fernandez A, Fildes JE. Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study. Artif Organs. 2022 Feb;46(2):259-272. doi: 10.1111/aor.14089. Epub 2021 Nov 26.
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Article