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

Key Points. Physiological normothermic machine perfusion kept kidneys viable for 12 hours with better hemodynamics, urine output, and metabolic stability than clinical normothermic machine perfusion. Physiological normothermic machine perfusion reduced injury (lower urinary neutrophil gelatinase-associated lipocalin), improved histology/appearance, and increased clinical suitability versus clinical normothermic machine perfusion. Prolonged physiological preservation could electivize surgery, improve early function, and expand donor kidney utilization. Background. Hypothermic donor kidney preservation contributes to graft injury, leading to substantial discard rates and peritransplant nephron loss. Normothermic machine perfusion may offer superior preservation, but current clinical protocols are restrictive because of 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 United Kingdom over a 12-hour perfusion period. Methods. Paired porcine kidneys underwent standard retrieval and cold storage before randomization to either cNMP or our pNMP. Both groups were perfused for 12 hours while monitoring hemodynamics, biochemistry, and urine output. Results. Kidneys preserved with pNMP exhibited superior perfusion, with improving hemodynamics and metabolic function within physiological ranges. Urine output was stable with a low concentration of the renal injury marker neutrophil gelatinase-associated lipocalin, indicating improved tissue viability. By contrast, cNMP kidneys exhibited evidence of hemodynamic compromise, with polyuria. Histological analyses of cNMP kidneys confirmed AKI. All pNMP kidneys were assessed as suitable for transplant on the basis of clinical assessment score, while several cNMP kidneys were considered marginal. Conclusions. The pNMP protocol improved preservation of donor kidneys compared with 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.