Physiological Normothermic Perfusion Enhances Kidney Preservation Versus the Established UK Normothermic Machine Perfusion Assessment Protocol

Background: Hypothermic donor kidney preservation contributes to graft injury, leading to substantial discard rates and peri-transplant nephron loss. Normothermic machine perfusion may offer superior preservation, but current clinical protocols are restrictive due to time dependent injury. On these grounds, we performed a paired preclinical evaluation of a novel physiological NMP (pNMP) protocol versus the current clinical NMP (cNMP) protocol used in the UK over a 12-hour perfusion period. Methods: Paired porcine kidneys underwent standard retrieval and cold storage before randomisation to either cNMP or our pNMP. Both groups were perfused for 12-hours while monitoring haemodynamics, biochemistry and urine output. Results: Kidneys preserved with pNMP exhibited superior perfusion, with improving haemodynamics and metabolic function within physiological ranges. Urine output was stable with a low concentration of the renal injury marker NGAL, indicating improved tissue viability. In contrast, cNMP kidneys exhibited evidence of haemodynamic compromise, with polyuria. Histological analyses of these kidneys confirmed acute kidney injury. All pNMP kidneys were assessed as suitable for transplant based on the clinical assessment score, while several cNMP kidneys were considered marginal. Conclusions: The pNMP protocol improved preservation of donor kidneys compared to the cNMP protocol. Successful prolonged organ preservation could transform clinical kidney transplantation by obviating night-implantation and has further potential benefits for improving post-transplant outcomes and expanding the donor pool.