Hemodiafiltration improves performance of 24 hour ex situ normothermic liver machine perfusion

BACKGROUND & AIMS: Performing ex situ normothermic machine perfusion (NMP) for ≥24 h represents an opportunity to evaluate and treat livers, but is limited by the lack of support from relevant extrahepatic organs. Incorporation of systems of renal replacement therapy, including hemodiafiltration (HDF), appears useful in this regard during prolonged ex situ liver NMP. This study aimed to demonstrate the impact and benefits associated with incorporation of continuous HDF during 24-h ex situ NMP in a relevant preclinical model, including transplantation and post-transplant follow-up. METHODS: Porcine livers (n = 28) underwent 24-h ex situ NMP with either partial perfusate exchange at 12 h and no HDF (NHDF, n = 11) or HDF initiated 2 h after NMP start (n = 17). Biochemical, histological, endothelial, and metabolomic parameters were assessed. A subset of grafts undergoing NMP + HDF (n = 8) were transplanted into recipients. RESULTS: Incorporation of HDF during NMP maintained stable pH and electrolyte levels, effectively preventing hypernatremia, hypochloremia, and hypocalcemia developing without HDF. HDF cleared metabolic wastes (e.g. urea) and inflammatory cytokines (IL-1B, IL-2, IL-6, IL-8, and IL-18), resulting in reduced injury and oxidative stress markers after 24 h (Suzuki score 0.8 ± 0.4 HDF vs. 2.7 ± 1.3 NHDF, p