Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome
Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome
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DOI：
10.1097/tp.0000000000000500
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发表时间：
2015-06-01
期刊：
影响因子：
6.2
通讯作者：
Seelen, Marc A.
中科院分区：
文献类型：
--
作者：
Damman, Jeffrey;Bloks, Vincent W.;Seelen, Marc A.
背景在过去的几十年里，提高肾移植后同种异体移植物存活率的策略已经指向肾损伤的依从性依赖性机制。相比之下，没有做出这样的努力来优化供体的器官质量。优化已故供体肾脏质量为改善肾移植结局开辟了新的可能性。方法.共554例肾活检标本取自脑死亡（DBD）捐赠肾和心源性死亡（DCD）捐赠肾，分别在捐赠前、冷缺血后和再灌注后进行。健康活体供肾活检作为对照。转录组学通过全基因组微阵列分析进行，然后进行功能途径分析。结果在器官回收和停止血液循环之前，与缺氧和补体-凝血级联相关的代谢途径是DBD供体中增强的主要途径。在第一次热缺血时间后，DCD供体中也富集了类似的途径。DCD移植物再灌注后不久，与缺氧延长和恶化相关的通路与受体移植物功能延迟相关。结论总之，这项大型已故供体研究显示，在器官回收之前，在血流停止之前，DBD供体中已经存在缺氧和补体和凝血途径的富集。因此，未来的干预治疗应针对供者的缺氧和补体-凝血级联反应，以改善受者的肾移植结局。
Background. In the last few decades, strategies to improve allograft survival after kidney transplantation have been directed to recipient-dependent mechanisms of renal injury. In contrast, no such efforts have been made to optimize organ quality in the donor. Optimizing deceased donor kidney quality opens new possibilities to improve renal allograft outcome. Methods. A total of 554 kidney biopsies were taken from donation after brain death (DBD) and donation after cardiac death (DCD) kidneys before donation, after cold ischemia and after reperfusion. Healthy living donor kidney biopsies served as controls. Transcriptomics was performed by whole genome microarray analyses followed by functional pathway analyses. Results. Before organ retrieval and before cessation of blood circulation, metabolic pathways related to hypoxia and complement-and-coagulation cascades were the major pathways enhanced in DBD donors. Similar pathways were also enriched in DCD donors after the first warm ischemia time. Shortly after reperfusion of DCD grafts, pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function in the recipient. Conclusion. In conclusion, this large deceased donor study shows enrichment of hypoxia and complement-and-coagulation pathways already in DBD donors before cessation of blood flow, before organ retrieval. Therefore, future intervention therapies should target hypoxia and complement-and-coagulation cascades in the donor to improve renal allograft outcome in the recipient.