Optimization of Rat Kidney Normothermic Machine Perfusion With Bovine Serum Albumin Perfusate: Improving Renal Function and Transplant Outcomes

Although normothermic machine perfusion (NMP) has been employed in clinical transplantation, the efficient and standardized long-term NMP strategies for small animals remain to be explored, which may significantly facilitate fundamental biomedical research and drug evaluation. We established a straightforward rat kidney ex vivo NMP system and explored the efficacy of different perfusates by comparing various parameters, including the perfusion and metabolic parameters, renal function, histological features, acute renal injury score, and inflammation. Additionally, we implanted the kidneys after NMP and demonstrated the effectiveness and safety by comparing the survival of recipients, acute renal injury, and graft function. The kidneys were able to produce urine during NMP, and the groups with fetal bovine serum (FBS) exhibited higher urine output compared to those supplemented with bovine serum albumin (BSA). Nonetheless, the BSA group displayed more stable perfusion resistance, enhanced oxygen consumption efficacy, superior renal tubule function in electrolyte reabsorption and excretion, and reduced vessel injury and tissue inflammation. All grafts were successfully transplanted, and the BSA group showed slighter injury than FBS on postoperative 1 and 7 days and was not significantly different from the cold storage group. A supporting kidney function in vitro was achieved using the optimized NMP method with the perfusate consisting of rat peripheral blood, RPMI-1640, and BSA. This novel NMP strategy in small animal models may benefit basic studies related to organ preservation, assessment, and intervention in the future. Graphical We established a rat kidney ex vivo normothermic machine perfusion system and evaluated different perfusates by assessing perfusion/metabolic parameters, renal function, histology, and inflammation. Implanting perfused kidneys, we confirmed efficacy and safety via recipient survival and graft function. The perfusate with rat peripheral blood, RPMI-1640, and BSA showed superior renal function and minimal organ injury, promising for organ preservation, assessment, and intervention studies.