Metabolomic perfusate analysis during kidney machine perfusion: the pig provides an appropriate model for human studies

Introduction: Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods: Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results: There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions: Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.

引言：低温机器灌注（Hypothermic Machine Perfusion, HMP）在肾脏移植领域展现出巨大应用前景，当前仍需开展实验研究以确定其最佳实施条件。猪肾脏被视为该研究的理想模型，其与人类肾脏器官拥有诸多共同特性。然而目前尚未明确，在低温缺氧条件下，猪肾脏的代谢水平是否可与人类肾脏相媲美。
方法：符合既定标准的人类肾脏（n=12）与猪肾脏（n=10）采用Organ Recovery Systems公司生产的LifePort肾脏转运仪1.0型及KPS-1灌注液开展低温机器灌注。分别于灌注45分钟及4小时时采集灌注液样本，并采用一维氢核磁共振光谱（1-D ¹H-NMR spectroscopy）技术完成代谢组学分析。
结果：本次研究鉴定得到的代谢物总数不存在种间差异。在分析的30种代谢物中，16种（占比53.3%）在猪与人类肾脏灌注液中的浓度水平相当。3-羟基丁酸（3-Hydroxybutyrate）的浓度变化速率在人类肾脏样本中更高（p<0.001）。其余29种代谢物（占比96.7%）的浓度变化速率在猪与人类样本中均无显著差异。
结论：尽管猪与人类肾脏在低温机器灌注过程中存在部分差异，但二者的代谢特征整体相似，猪肾脏可作为人类相关研究的有效模型。