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持续常温体外肾脏灌注改善心脏死亡后捐献猪肾移植的移植物功能

Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation.

作者信息

Kaths J Moritz, Echeverri Juan, Chun Yi Min, Cen Jun Yu, Goldaracena Nicolas, Linares Ivan, Dingwell Luke S, Yip Paul M, John Rohan, Bagli Darius, Mucsi Istvan, Ghanekar Anand, Grant David R, Robinson Lisa A, Selzner Markus

机构信息

1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 2 Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 3 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 4 Department of General, Visceral, and Transplant Surgery, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. 5 Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 6 Departments of Surgery (Urology) and Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada. 7 Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 8 Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 9 Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

Transplantation. 2017 Apr;101(4):754-763. doi: 10.1097/TP.0000000000001343.

Abstract

BACKGROUND

Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion.

METHODS

We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation.

RESULTS

Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029).

CONCLUSIONS

Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.

摘要

背景

循环死亡后器官捐献(DCD)是目前临床实践中增加供体库的方法。低温保存对肾移植功能有不良影响。因此,目前的研究重点是研究替代保存技术,如常温灌注。

方法

在猪DCD自体移植模型中,我们将持续压力控制的常温离体肾脏灌注(NEVKP)与静态冷藏(SCS)进行了比较。在30分钟热缺血后,从30千克的约克夏猪身上取出右肾,用8小时的NEVKP或置于4°C的组氨酸-色氨酸-酮戊二酸溶液(SCS)中保存,随后进行肾脏自体移植。

结果

在整个NEVKP过程中,电解质和pH值保持稳定。灌注过程中肾内阻力降低(0小时,1.6±0.51毫米汞柱/分钟 vs 7小时,0.34±0.05毫米汞柱/毫升/分钟,P = 0.005)。灌注液乳酸浓度也降低(0小时,10.5±0.8 vs 7小时,1.4±0.3毫摩尔/升,P < 0.001)。细胞损伤标志物乳酸脱氢酶和天冬氨酸转氨酶一直较低(乳酸脱氢酶<100 U/L,低于分析仪范围;天冬氨酸转氨酶0小时,15.6±9.3 U/L vs 7小时,24.8±14.6 U/L,P = 0.298)。自体移植后,用NEVKP保存的肾移植在第1至7天血清肌酐较低(P < 0.05)且峰值较低(NEVKP,5.5±1.7毫克/分升 vs SCS,11.1±2.1毫克/分升,P = 0.002)。第4天,用NEVKP保存的肾脏肌酐清除率增加(NEVKP,39±6.4 vs SCS,18±10.6毫升/分钟;P = 0.012)。第3天,NEVKP组血清中性粒细胞明胶酶相关脂质运载蛋白较低(1267±3

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