Hosgood, S. A. | bioRxiv Science

bioRxiv2026

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

Normothermic machine perfusion (NMP) typically uses red blood cell (RBC)-based perfusates, with associated challenges, including free haem-driven ferroptotic tubular injury. Acellular perfusates avoid these risks. Subnormothermic machine perfusion (SMP, 32{degrees}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 eight 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{degrees}C) to simulate reperfusion. Upregulation of transcriptomic ischaemia-reperfusion injury (IRI) related pathways and downregulation of oxidative phosphorylation at 6 hours SMP and 4 hours 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 to 6 hours RBC-NMP at 37{degrees}C, both SMP groups showed equivalent pro-inflammatory pathway activation and oxidative phosphorylation depletion. Thus, we provide 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.

physiology↗

bioRxiv2019

Investigation of the transcriptional profile of human kidneys during machine perfusion reveals potential benefits of haemoadsorption

Transplantation is the optimal treatment for most patients with end stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to re-condition marginal organs but the mechanisms by which NMP might benefit transplant kidneys are not fully understood. Furthermore, the question of whether removal of pro-inflammatory mediators from the perfusate might offer additional benefits in optimising kidneys prior to transplantation has not been addressed. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global transcriptome of kidneys, and then went on to investigate the impact of adding a haemoadsorption device to the NMP circuit. We found that cold storage significantly reduced the expression of inflammatory genes, but also of genes required for energy generation such as those encoding oxidative phosphorylation (OXPHOS) enzymes. In contrast, during NMP, there was marked upregulation OXPHOS genes, as well as a number of immune and inflammatory pathway genes. The induction of inflammatory genes during NMP was substantially attenuated by the addition of a haemoadsorber to the perfusion circuit, which also further increased OXPHOS pathway gene expression. Together, our data suggest that absorption of pro-inflammatory mediators from the perfusate represents a useful intervention that may further improve organ viability and should be tested in clinical practice.\n\nSingle sentence summary: The use of a haemoadsorber during machine perfusion reduces inflammatory gene expression, with potential benefits for kidney transplantation.

physiology↗