Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, Groningen, the Netherlands.
PLoS One. 2020 Mar 10;15(3):e0229566. doi: 10.1371/journal.pone.0229566. eCollection 2020.
In porcine kidney auto-transplant models, red blood cells (RBCs) are required for ex-vivo normothermic machine perfusion (NMP). As large quantities of RBCs are needed for NMP, utilising autologous RBCs would imply lethal exsanguination of the pig that is donor and recipient-to-be in the same experiment. The purpose of this study was to determine if an isolated porcine kidney can also be perfused with allogeneic porcine or human RBCs instead. Porcine kidneys, autologous and allogeneic blood were obtained from a local slaughterhouse. Human RBCs (O-pos), were provided by our transfusion laboratory. Warm ischaemia time was standardised at 20 minutes and subsequent hypothermic machine perfusion lasted 1.5-2.5 hours. Next, kidneys underwent NMP at 37°C during 7 hours with Williams' Medium E and washed, leukocyte depleted RBCs of either autologous, allogeneic, or human origin (n = 5 per group). During perfusion all kidneys were functional and produced urine. No macroscopic adverse reactions were observed. Creatinine clearance during NMP was significantly higher in the human RBC group in comparison with the allogeneic group (P = 0.049) but not compared to the autologous group. The concentration of albumin in the urine was significantly higher in the human RBC group (P <0.001) compared to the autologous and allogeneic RBC group. Injury marker aspartate aminotransferase was significantly higher in the human RBC group in comparison with the allogeneic group (P = 0.040) but not in comparison with the autologous group. Renal histology revealed glomerular and tubular damage in all groups. Signs of pathological hyperfiltration and microvascular injury were only observed in the human RBC group. In conclusion, perfusion of porcine kidneys with RBCs of different origin proved technically feasible. However, laboratory analysis and histology revealed more damage in the human RBC group compared to the other two groups. These results indicate that the use of allogeneic RBCs is preferable to human RBCs in a situation where autologous RBCs cannot be used for NMP.
在猪肾自体移植模型中，需要红细胞（RBC）才能进行体外常温机器灌注（NMP）。由于 NMP 需要大量 RBC，因此如果要使用自体 RBC，则意味着供体和实验中即将接受的受体猪将因致命性放血而死亡。本研究旨在确定是否可以用同种异体猪或人 RBC 代替分离的猪肾进行灌注。从当地屠宰场获得猪肾、自体和同种异体血液，人类 RBC（O 阳性）由我们的输血实验室提供。热缺血时间标准化为 20 分钟，随后低温机器灌注持续 1.5-2.5 小时。接下来，在 37°C 下用 Williams' Medium E 对肾脏进行 NMP 7 小时，并使用来自自体、同种异体或人类来源的白细胞去除 RBC 进行冲洗（每组 5 个）。在灌注过程中，所有肾脏均具有功能并产生尿液。未观察到宏观不良反应。与同种异体组相比，NMP 期间人 RBC 组的肌酐清除率显著更高（P = 0.049），但与自体组相比则无差异。与自体和同种异体 RBC 组相比，人 RBC 组尿液中的白蛋白浓度显著更高（P <0.001）。与同种异体组相比，人 RBC 组的天冬氨酸转氨酶损伤标志物显著更高（P = 0.040），但与自体组相比则无差异。组织学检查显示所有组均有肾小球和肾小管损伤。仅在人 RBC 组观察到病理高滤过和微血管损伤的迹象。总之，用不同来源的 RBC 灌注猪肾在技术上是可行的。然而，实验室分析和组织学检查显示，与其他两组相比，人 RBC 组的损伤更大。这些结果表明，在无法使用自体 RBC 进行 NMP 的情况下，使用同种异体 RBC 优于人 RBC。
