国内首例人弃肾长时间体外常温机械灌注经验探索

Exploration on the experience of long-term external normothermic machine perfusion of discarded human kidney for the first time in China

目的探讨常温机械灌注(normothermic machine perfusion,NMP)对临床弃肾的长时间保存的价值及修复作用。方法收集1例临床弃用供肾,用回收血液对其进行体外持续NMP 9 h,记录此过程中肾脏外观、灌注液前后血气和生化以及肾脏病理的动态变化。结果NMP的第2~5小时,肾脏外观呈现粉红色,体外NMP评分(ex vivo normothermic perfusion assessment score,EVNP)为Ⅰ级;第6小时及之后,肾脏外观呈现暗红色,EVNP为Ⅲ级。NMP的前6 h,肾灌注血流量都能很好地维持150 ml/min以上;而第6小时之后,肾灌注流量大幅度降低,到结束时,肾灌注流量仅为50 ml/min。灌注的整个过程中,尿量均能维持在100 ml/h左右。在灌注的前5 h PO_(2)都能保持100 mmHg以上,从第6小时开始,PO_(2)已经下降至人体正常生理值(80 mmHg)且持续下降,至灌注结束时PO_(2)已经接近0 mmHg。在NMP的前5 h,血液和尿液中的K+浓度变化有着很好的一致性,但乳酸水平却一直在不断上升。此外,病理结果发现,灌注第4小时与灌注前零点穿刺的组织病理相比无明显改变,并且肾小球内的纤维素性血栓较灌注前有所改善;而灌注第6小时和灌注结束前肾组织病理较之前有明显的恶化,肾小球血管内有大量的血栓形成,同时出现了肾小管萎缩和肾小管急性坏死。结论NMP可以实现对扩大标准供体供肾移植前的评估,并且在一定程度上证明了NMP在肾脏应用的可行性以及其修复潜能。同时,NMP也为扩大供肾来源和体外器官预处理提供了新的途径。

Objective To explore the long-term preservation value and repair effect of normothermic machine perfusion(NMP)on clinically discarded kidneys.Methods A case of clinical discarded donor kidney was collected,and NMP was carried out in vitro for 9 hours with recovered blood.The dynamic changes of renal appearance,blood gas and biochemistry analysis of perfusate and renal pathology were recorded.Results In the second to fifth hour of NMP,the appearance of renal was pink and ex vivo normothermic perfusion assessment score(EVNP)was gradeⅠ.While,the sixth hour and beyond of NMP,the appearance of kidney turned to dark red and EVNP was gradeⅢ.The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that,and at the end,was only 50 ml/min.During the whole process of perfusion,urine output was maintained at about 100 ml/h.PO_(2) remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour,was lower than 80 mmHg and continued to decline,and was close to 0 at the end of perfusion.The results showed that although the K+concentration changes in blood and urine in the first 5 hours of NMP had a good consistency,the lactic acid level had been rising.In addition,there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture,and the fibrinous thrombus in glomeruli was improved compared with that before perfusion.However,at the sixth hour after perfusion and before the end of perfusion,the pathological changes of renal tissue were significantly worse.There were a large of thrombosis in glomerular blood vessels,renal tubular atrophy and acute tubular necrosis.Conclusions NMP can realize the evaluation of extended criteria donors before transplantation,and it proves the feasibility and repair potential of NMP in kidney to a certain extent.At the same time,NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.