From the Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ont. (Juriasingani, Vo, Akbari, Grewal, Zhang, Sener); the Matthew Mailing Centre for Translational Transplant Studies, University Hospital, London Health Sciences Centre, London, Ont. (Juriasingani, Vo, Akbari, Grewal, Zhang, Jiang, Sener); the Undergraduate Medical Education-MD program, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ont. (Vo); the Department of Pathology, Schulich School of Medicine & Dentistry, University of Western, London, Ont. (Haig); the Department of Surgery, Schulich School of Medicine & Dentistry, St. Joseph's Health Care, London, Ont. (Sener); and the Multi Organ Transplant Program, University Hospital, London Health Sciences Centre, London, Ont. (Sener).
From the Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ont. (Juriasingani, Vo, Akbari, Grewal, Zhang, Sener); the Matthew Mailing Centre for Translational Transplant Studies, University Hospital, London Health Sciences Centre, London, Ont. (Juriasingani, Vo, Akbari, Grewal, Zhang, Jiang, Sener); the Undergraduate Medical Education-MD program, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ont. (Vo); the Department of Pathology, Schulich School of Medicine & Dentistry, University of Western, London, Ont. (Haig); the Department of Surgery, Schulich School of Medicine & Dentistry, St. Joseph's Health Care, London, Ont. (Sener); and the Multi Organ Transplant Program, University Hospital, London Health Sciences Centre, London, Ont. (Sener)
Can J Surg. 2022 Mar 15;65(2):E193-E202. doi: 10.1503/cjs.013920. Print 2022 Mar-Apr.
The increasing use of kidneys from donations after cardiac death (DCD) for renal transplantation is hindered by negative outcomes owing to organ injury after prolonged warm and cold ischemia-reperfusion. Recently, hydrogen sulfide (HS) has shown cytoprotective effects against ischemia-reperfusion injury; however, its effectiveness in the context of DCD renal transplantation is unknown.
We tested a novel 30-day in vivo syngeneic murine model of DCD renal transplantation, in which the donor kidney was clamped for 30 minutes and stored for 18 hours in cold University of Wisconsin (UW) solution or UW with 150 μM sodium hydrogen sulfide (UW + NaHS) before transplantation. We also tested a 7-day in vivo porcine model of DCD renal autotransplantation, in which the left kidney was clamped for 60 minutes and preserved for 24 hours using hypothermic perfusion with UW or UW + 150 μM NaHS before autotransplantation. We collected blood and urine samples periodically, and collected kidney samples at the end point for histopathology and quantitative reverse transcription polymerase chain reaction.
Rats that received HS-treated kidneys showed significantly higher survival, faster recovery of graft function and significantly lower acute tubular necrosis than controls. Pig kidneys perfused with UW + NaHS showed significantly higher renal blood flow and lower renal resistance than control kidneys after 24 hours of perfusion. After autotransplantation, pigs that received HS-treated kidneys showed significantly lower serum creatinine on days 1 and 7 after transplantation. Rat and pig kidneys treated with HS also showed more protective gene expression profiles than controls.
Our findings support the potential use of HS-supplemented UW solution during cold storage as a novel and practical means to improve DCD graft survival and function.
由于长时间的温热缺血再灌注导致的器官损伤，心脏死亡后捐献（DCD）的肾脏用于肾移植的数量不断增加，但由此产生的不良后果也随之增加。最近，硫化氢（HS）已显示出对缺血再灌注损伤的细胞保护作用；然而，其在 DCD 肾移植中的效果尚不清楚。
我们测试了一种新的 30 天体内同基因小鼠 DCD 肾移植模型，在该模型中，供体肾脏夹闭 30 分钟，然后在 UW 溶液或含 150μM 氢硫化钠（UW+NaHS）的 UW 溶液中冷保存 18 小时，再进行移植。我们还测试了一种 7 天的体内猪 DCD 肾自体移植模型，在该模型中，左肾夹闭 60 分钟，然后使用 UW 或 UW+150μM NaHS 的低温灌注保存 24 小时，再进行自体移植。我们定期采集血液和尿液样本，并在终点收集肾脏样本进行组织病理学和定量逆转录聚合酶链反应分析。
接受 HS 处理的肾脏的大鼠的存活率明显更高，移植物功能恢复更快，急性肾小管坏死明显更低。用 UW+NaHS 灌注的猪肾在灌注 24 小时后，肾血流量明显更高，肾阻力明显更低。自体移植后，接受 HS 处理的肾脏的猪在移植后第 1 和第 7 天的血清肌酐明显更低。接受 HS 处理的大鼠和猪的肾脏也显示出比对照组更具保护作用的基因表达谱。
我们的研究结果支持在冷储存期间使用 HS 补充 UW 溶液作为一种新的实用方法来提高 DCD 移植物的存活率和功能。
