R & D, Emergentec Biodevelopment GmbH, Vienna, Austria.
Transplantation. 2009 Aug 15;88(3 Suppl):S14-9. doi: 10.1097/TP.0b013e3181af65b5.
Ischemia reperfusion injury (IRI) is a choreographed process leading to delayed graft function (DGF) and reduced long-term patency of the transplanted organ. Early identification of recipients of grafts at risk would allow modification of the posttransplant management, and thereby potentially improve short- and long-term outcomes. The recently emerged "omics" technologies together with bioinformatics workup have allowed the integration and analysis of IRI-associated molecular profiles in the context of DGF. Such a systems biological approach promises qualitative information about interdependencies of complex processes such as IRI regulation, rather than offering descriptive tables of differentially regulated features on a transcriptome, proteome, or metabolome level leaking the functional, biological framework. In deceased-donor kidney transplantation as the primary causative factor resulting in IRI and DGF, a distinct signature and choreography of molecular events in the graft before harvesting seems to be associated with subsequent DGF. A systems biological assessment of these molecular changes suggests that processes along inflammation are of pivotal importance for the early stage of IRI. The causal proof of this association has been tested by a double-blinded, randomized, controlled trial of steroid or placebo infusion into deceased donors before the organs were harvested. Thorough systems biological analysis revealed a panel of biomarkers with excellent discrimination. In summary, integrated analysis of omics data has brought forward biomarker candidates and candidate panels that promise early assessment of IRI. However, the clinical utility of these markers still needs to be established in prospective trials in independent patient populations.
缺血再灌注损伤（IRI）是一个精心编排的过程，导致移植物延迟功能（DGF）和移植器官的长期通畅性降低。早期识别有风险的移植受者，将允许修改移植后的管理，从而有可能改善短期和长期结果。新兴的“组学”技术与生物信息学研究一起，允许在 DGF 背景下整合和分析与 IRI 相关的分子谱。这种系统生物学方法有望提供关于IRI 调节等复杂过程相互依存关系的定性信息，而不是在转录组、蛋白质组或代谢组水平上提供差异调节特征的描述性表格，从而泄露功能、生物学框架。在以死亡供体肾移植为主要导致 IRI 和 DGF 的原因的情况下，在收获前移植物中似乎存在与随后的 DGF 相关的独特分子事件特征和编排。对这些分子变化的系统生物学评估表明，沿炎症过程的过程对 IRI 的早期阶段至关重要。这种关联的因果关系已通过一项在器官收获前对死亡供体进行类固醇或安慰剂输注的双盲、随机、对照试验进行了测试。彻底的系统生物学分析揭示了具有出色区分能力的生物标志物面板。总之，对组学数据的综合分析提出了具有早期评估 IRI 潜力的生物标志物候选者和候选者组合。然而，这些标记物的临床实用性仍需要在独立患者人群的前瞻性试验中建立。
