Current kidney perfusion protocols are not optimized for addressing the physiological and metabolic needs of the kidney. normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12-hour normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience.

中文翻译：

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离体常温灌注期间已故供体肾功能和支链氨基酸代谢


目前的肾脏灌注方案并未针对满足肾脏的生理和代谢需求进行优化。常温灌注可用于区分高危肾脏，以确定是否适合移植。在这里，我们评估了在 12 小时常温灌注期间被认为不适合移植的 8 个已故供体肾脏中组织代谢变化与肾损伤生物标志物和功能参数变化的关联。根据血流量和尿量，将肾脏分为表现良好和表现不佳的肾脏。已故肾捐献者的平均年龄为43岁，平均冷缺血时间为37小时。表现良好的患者的尿量和肌酐清除率逐渐增加，并在灌注后六小时达到峰值。与峰值功能差异相对应的表现良好者相比，表现不佳者在六小时内的尿中性粒细胞明胶酶相关脂质运载蛋白高出 71 ng/ml（95% 置信区间 1.5, 140）。器官性能的区别在于支链氨基酸代谢的组织代谢差异，并且它们的组织水平与所有肾脏在六小时内的尿量呈负相关。组织脂质分析显示，在早期灌注时间点，包括甘油脂和鞘脂在内的膜结构成分的积累突出显示了表现不佳的人。因此，我们发现常温灌注期间肾功能恢复需要六个小时，支链氨基酸代谢可能是器官功能和恢复力的主要决定因素。