Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo
Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo
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DOI：
10.1016/j.ekir.2019.05.013
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发表时间：
2019-09-01
影响因子：
6
通讯作者：
Luke, Patrick P. W.
中科院分区：
文献类型：
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作者：
Bhattacharjee, Rabindra N.;Ruthirakanthan, Aushanth;Luke, Patrick P. W.
简介：目前在无氧寒冷条件下保存供体肾脏的方法只能最低程度地保护肾脏免受缺血再灌注损伤（IRI）的影响，而缺血再灌注损伤是临床移植并发症的主要来源。然而，由于缺乏促进血液在高温下灌注的理想灌注机制，目前用含氧灌注保护肾脏并不可行。在这里，我们设计了一种创新的肾泵回路系统，可以在灵活的温度、压力和氧合下灌注血液或无细胞氧载体。我们已经测试了该装置来研究心源性死亡捐献（DCD）肾脏的猪模型的最佳储存条件。方法：在原位交叉夹紧肾蒂30分钟后取出猪肾脏。血液的停止模拟人类的心后死亡并模拟 DCD 热缺血性损伤。冲洗获得的肾脏并进行静态冷藏(SCS)4小时。为了进行温灌注，将肾脏插管进行脉动含氧血液灌注：PlasmaLyte 在 15°C、22°C 和 37°C 下持续 4 小时。为了模拟移植后情况，所有肾脏在 37°C 下再灌注血液 4 小时。结果：与所有其他组相比，22°C 灌注可显着减少急性肾小管坏死 (ATN)、细胞凋亡和肾损伤标记物、Toll 样受体信号转导和细胞因子的产生。它与最大肾血流量和尿量相关。在这种条件下，15℃保存的肾脏在2小时内就会形成血栓。 Martius 猩红蓝染色证实 22 摄氏度是最大程度减少出血和血栓的最佳温度。结论：我们的新研究表明，接近室温的含氧灌注可提供最佳的供体肾脏储存条件。
Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys.Methods: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 degrees C, 22 degrees C, and 37 degrees C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 degrees C.Results: Compared with all other groups, 22 degrees C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 degrees C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 degrees C was the optimal temperature to minimize hemorrhage and blood clots.Conclusion: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions.