高RIPK3表达与早期肾移植失败风险较高相关。
High RIPK3 expression is associated with a higher risk of early kidney transplant failure.
作者信息
Wahida Adam, Schmaderer Christoph, Büttner-Herold Maike, Branca Caterina, Donakonda Sainitin, Haberfellner Flora, Torrez Carlos, Schmitz Jessica, Schulze Tobias, Seibt Tobias, Öllinger Rupert, Engleitner Thomas, Haller Bernhard, Steiger Katja, Günthner Roman, Lorenz Georg, Yabal Monica, Bachmann Quirin, Braunisch Matthias C, Moog Philipp, Matevossian Edouard, Aßfalg Volker, Thorban Stefan, Renders Lutz, Späth Martin R, Müller Roman-Ulrich, Stippel Dirk L, Weichert Wilko, Slotta-Huspenina Julia, von Vietinghoff Sibylle, Viklicky Ondrej, Green Douglas R, Rad Roland, Amann Kerstin, Linkermann Andreas, Bräsen Jan Hinrich, Heemann Uwe, Kemmner Stephan
机构信息
Medical Department III of Hematology and Oncology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany.
Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany.
出版信息
iScience. 2023 Sep 17;26(10):107879. doi: 10.1016/j.isci.2023.107879. eCollection 2023 Oct 20.
Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.
肾缺血再灌注损伤（IRI）与移植肾存活率降低相关，肾移植后冷缺血时间每增加一小时，移植肾失败和死亡的风险就会增加。受体相互作用蛋白激酶3（RIPK3）是坏死性凋亡（一种受调控的细胞死亡形式）的关键效应因子。在此，我们评估了肾移植IRI后首个关于人类RIPK3表达的数据集。初步分析纳入了374份再灌注开始10分钟后取自移植肾的基线活检样本。RIPK3主要在近端肾小管细胞和远端肾小管细胞中检测到，这两种细胞均受IRI影响。生存分析显示，在多变量分析中，高RIPK3表达与一年移植失败风险显著升高相关，且是一年（死亡删失）移植失败的独立预后因素，与供体和受体相关风险因素无关。RIPK3评分还与尸体供肾、冷缺血时间及肾小管损伤程度相关。
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