SRS301 - Subnormothermic machine perfusion of human kidneys using an acellular perfusion solution is non-inferior to red blood cell based perfusion

Abstract Background Normothermic machine perfusion (NMP) preserves kidneys in a near-physiological state, allowing viability assessment and intervention. NMP typically uses red blood cell (RBC)-based perfusates, with associated challenges, including blood type compatibility, haemolysis, and free haem–driven ferroptotic tubular injury. Acellular perfusates avoid these risks. Subnormothermic machine perfusion (SMP, 32°C) may reduce metabolic demands while preserving organ viability, but the effect of perfusate type under these conditions remains unclear. Methods In a paired experimental design, kidneys from eight deceased donors were randomized 1:1 to 6 h of SMP with RBC-based (RBC-SMP) or acellular perfusate (SNAP), followed by 4 h of RBC-based NMP (37°C) to simulate reperfusion. Bulk RNA sequencing, transcriptomic pathway scoring, urinary biomarkers, and histology were used to compare perfusion methods. Publicly available RBC-NMP transcriptomic data were integrated for comparison. Results Transcriptional comparison showed no difference in pathways related to ischaemia-reperfusion injury (IRI; TNFα via NFκB, Allograft Rejection, Inflammatory Response) and Oxidative Phosphorylation, at 6 h SMP and 4 h reperfusion between RBC-SMP and SNAP kidneys. Similarly, metabolism-associated transcriptional pathways, urinary tubular injury biomarkers (NGAL, L-FABP, TIMP2, IGFBP7), and histological injury were similar between groups. Compared to 6 h of RBC-NMP at 37°C, both subnormothermic groups showed less depletion of oxidative phosphorylation with similar IRI levels, suggesting preserved mitochondrial function. Conclusions Acellular subnormothermic kidney perfusion is equivalent to RBC-based SMP at the transcriptomic, metabolic, and tubular injury level. Our data support the clinical feasibility of SNAP as a safe, logistically simple alternative for kidney preservation.