Weissenbacher Annemarie, Voyce Daniel, Ceresa Carlo D L, Soares Maria F, Roberts Ian S, Hunter James P, Cook Andrew, Ploeg Rutger J, Coussios Constantin C, Friend Peter J
Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Transplant Direct. 2020 Mar 13;6(4):e541. doi: 10.1097/TXD.0000000000000985. eCollection 2020 Apr.
The study compares urine recirculation (URC) to urine replacement (UR) with Ringer's lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device.
Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected.
Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; = 0.02. There appeared to be no differences in baseline tubular condition with and without URC.
URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.
本研究在猪常温肾脏机器灌注(NMP)模型中,使用临床前原型设备,将尿液再循环(URC)与使用乳酸林格氏液的尿液置换(UR)进行比较。
成对的肾脏完好无损地获取(如同活体供肾肾切除术)并依次进行灌注。猪肾(n = 10)被分配至接受URC的NMP组(n = 5)或接受容量置换的NMP组(n = 5)。一对肾脏的首次或第二次灌注(URC或UR)的冷缺血时间分别为2小时或27小时。使用经过白细胞过滤的自体血灌注液,进行长达24小时的NMP。监测灌注参数、生化/代谢参数并采集样本。
两组均实现了生理平均动脉压和血流,但仅URC能维持。URC组观察到显著更高的动脉血流(326.7±1.8对242.5±14.3 mL/分钟,P = 0.001)。URC组灌注液钠水平更低,为129.6±0.7对170.3±2.7 mmol/L,P < 0.001)。仅URC组观察到稳定的生理pH水平。URC组灌注液乳酸水平更低(2.2±0.1对7.2±0.5 mmol/L,P < 0.001)。此外,URC组每小时尿量更低且更接近生理水平(150对548 mL/小时,P = 0.008)。使用URC进行常温肾脏灌注与更长的可实现灌注持续时间相关:所有实验的目标是24小时灌注,但并非每种情况都能实现。URC组的平均灌注时间为17.3±9.2小时,而UR组的NMP为5.3±1.3小时;P = 0.02。有无URC时的基线肾小管状况似乎没有差异。
URC有助于在猪模型中进行长期肾脏NMP。仅URC能在整个灌注期实现灌注液内环境稳定和肾动脉血流稳定,且与冷缺血时间长短无关。