Abstract:

Objective Preliminary study on the repair effect of normothermic mechine perfusion（NMP）on acute kidney injury（AKI）of kidneys from cardiac death donors. Methods In vitro continuousNMP was used for cardiac-death pig kidneys . The blood gas biochemical indexes of the perfusion fluid and urine as well as the kidney pathological indexes during perfusion were recorded and analyzed. Results Ten pig kidneys were perfused with NMP in this study，of which 9 were perfused with single kidney，and 1 was perfused combined with liver. After the perfusion started，the kidneys were filled quickly and the surface tension was rich. About 5 min after the perfusion，the kidneys became bright red. The urine output of the kidneys increased at the initial stage of perfusion，reached the extreme value at（3.2±1.5）h on average after perfusion，and then decreased slowly. About 6 h later，the appearance of the kidneys turned dull color. The cross-section of the kidneys showed obvious hemorrhage in the renal pelvis and calyx，and the renal cortex and medulla were slightly bloody with soft and loose appearance. The normal perfusion flow rate increased gradually，reached peak after 2 ~ 3 hours of perfusion，and then maintained at a stable level. PaO2 was basically maintained in the range of 350 ~ 450 mmHg（1 mmHg ＝ 0.133 kPa）；PaCO2 varied greatly among the groups，mostly fluctuating at 15 ~ 60 mmHg，while each of perfusion individuals maintained a relatively stable level. The Na+ concentration fluctuated slightly in the early process of perfusion，and reached a stable level after about 3 ~ 4 h and was close to the normal value range. The K+ and Ca2+ concentrations were fluctuated within the physiological range. The lactic acid level of single-kidney perfusion increased progressively，while the lactic acid level of kidney-liver combined perfusion gradually decreased and then stabilized at a low level. The cross-section of the kidneys showed no obvious bleeding in the renal pelvis and calyx after 9 h of liver-kidney combined perfusion，and the renal cortex and medulla were bloodless and normal in appearance. The H&E pathological results showed that the damage of the globules and tubules gradually and slowly increased during the perfusion process，which suggested that the Normothermic Mechine Perfusion might delay the progress of the globular and tubule damage. Conclusion NMP can provide an environment close to the physiological state for isolated kidneys，and may have a certain repair effect on AKI. Therefore，NMP is expected to expand the source of donor kidneys and increase the rate of kidney transplantationin patients with end-stage renal disease for better prognosis and quality of life. In addition，liver-kidney combinedperfusion had better renal appearance and lactic acid levels than single-kidney perfusion，but no advantage in perfusion time，urine output，and pathological results. Above conclusions need to be supported by further large sample research.

Key words:

Normothermic mechine perfusion , Cardiac death donor kidney , Liver-kidney combined perfusion, Extended-standard kidney donor

摘要：

目的 初步探讨常温机械灌注（normothermic machine perfusion，NMP）对心脏死亡后急性 肾小管损伤（acute kidney injury，AKI）肾脏的修复效果。方法 利用持续常温机械灌注技术对心死亡猪肾进行体外持续灌注。对灌注过程中灌注液及尿液血气生化指标、肾脏外观以及病理指标进行记录和分析。结果 本研究共灌注猪肾 10 例，其中 9 例为单肾常温机械灌注，1 例为肝肾联合常温机械灌注。灌注开始后肾脏均迅速充盈且表面富有张力，约灌注 5 min 后肾脏整体呈均匀鲜红色。 肾脏的尿量在灌注初始阶段缓慢上升，并平均在灌注后（3.2±1.5）h 达到极值，而后缓慢下降。约 6 h 后肾外观颜色变暗，呈暗紫色 ； 灌注结束后的肾脏剖面显示肾盂肾盏出血明显，肾皮髓质有轻微血色，质感软绵疏松。正常灌注流速均逐 渐升高，在约第 2 ~ 3 小时达到峰值，随后保持稳定水平。血氧分压（partial pressure of blood oxygen，PaO2） 基本维持在 350 ~ 450 mmHg（1 mmHg ＝ 0.133 kPa）范围 ；二氧化碳分压（partial pressure of carbon dioxide，PaCO2）各组间差别较大，大都波动在 15 ~ 60 mmHg，灌注个体则维持在较为稳定的水平。灌注早期过程中Na+ 浓度略有波动，在约 3 ~ 4 h 后达到稳定水平并接近正常值范围，K+ 以及 Ca2+ 离子浓度均较为稳定且波动在生理范围 ；单肾灌注的乳酸水平呈进行性升高，而肝肾联合灌注时乳酸水平则逐渐下降并稳定在较低水平 ；且肝肾联合灌注 9 h 后肾脏剖面显示肾盂肾盏出血不明显，肾皮髓质无血色，质地较为正常。HE 染色病理结果显示小球及小管的损伤在灌注过程中缓慢加重，这提示常温机械灌注可能延缓了小球及小管损伤的进展。结论 NMP 可以为离体肾脏提供接近生理状态的环境，可能对 AKI 肾脏具有一定的修复作用。因此 NMP 有望扩大供肾来源，提高终末期肾病患者的肾移植率以获得更好的预后和生活质量。此外，肝肾联合灌注的肾脏外观以及乳酸水平较单肾灌注更优，但是灌注时长、尿量以及病理结果并无优势。以上结论有待进一步大样本研究数据支持。

关键词:

常温机械灌注 , 心死亡供肾 , 肝肾联合灌注 , 扩大标准供肾