Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study

• Published in: Artificial organs 2022-02, Vol.46 (2), p.259-272
• Main Authors: 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, Fildes, James E
• Format: Article
• Language: English
• Subjects: Acidosis; Acidosis - prevention & control; Animal models; Animals; Bicarbonates; Circuits; Cold storage; Composite Tissue Allografts; Cryopreservation; Cytokines; Deoxyribonucleic acid; DNA; Electrolytes; Forelimb; Homogeneity; Inflammation; Inflammation - prevention & control; Infrared imaging; Kidney - physiology; Kidneys; Lactic acid; Metabolic acidosis; Metabolism; Perfusion; Perfusion - methods; pH effects; Reperfusion; Reperfusion Injury; Sus scrofa; Thermal imaging
• ISSN: 0160-564X; 1525-1594
• DOI: 10.1111/aor.14089

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. 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. 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. The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis.