A comparative analysis of acellular versus red cell-based subnormothermic machine perfusion in human kidney...

Normothermic machine perfusion (NMP) typically uses red blood cell (RBC)-based perfusates, which are associated with logistical challenges. 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. In a paired experimental design, kidneys from 8 deceased donors were randomized 1:1 to 6 hours of SMP with RBC-based (RBC-SMP) or acellular perfusate (SNAP), followed by 4 hours of RBC-based NMP (37 °C) to simulate reperfusion. Upregulation of transcriptomic ischemia-reperfusion injury-related pathways and downregulation of oxidative phosphorylation at 6 hours of SMP and 4 hours of reperfusion were similar between RBC-SMP and SNAP kidneys. No differences were observed between groups in transcriptional profiles, metabolic pathway scores, urinary tubular injury biomarker concentrations, or histology. We integrated publicly available NMP transcriptomic data for comparison, demonstrating that compared with 6 hours of RBC-NMP at 37 °C, both SMP groups showed equivalent proinflammatory pathway activation and oxidative phosphorylation depletion. Thus, we provided evidence that SNAP maintains kidneys with equivalent transcriptional and urinary tubular injury biomarker profiles to RBC-SMP. These findings support the feasibility of SNAP for clinical translation in future studies.