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Microvasculature partial endothelial mesenchymal transition in early posttransplant biopsy with acute tubular necrosis identifies poor recovery renal allografts.
American Journal of Transplantation ( IF 8.9 ) Pub Date : 2020-03-13 , DOI: 10.1111/ajt.15847
Yi-Chun Xu-Dubois 1, 2, 3 , Pedram Ahmadpoor 3 , Isabelle Brocheriou 4 , Kevin Louis 1 , Nadia Arzouk Snanoudj 5 , Philippe Rouvier 4 , Jean-Luc Taupin 6, 7 , Anthony Corchia 1 , Pierre Galichon 1, 3 , Benoit Barrou 5 , Sébastien Giraud 8, 9 , Thierry Hauet 8, 9, 10 , Chantal Jouanneau 1 , Anita Rodenas 11 , Sandrine Placier 1 , Aissata Niasse 1 , Souhila Ouchelouche 1 , Ben-Youssef Naimi 12 , Elsa Akil 12 , Alexandre Hertig 1, 3, 5 , David Buob 1, 11 , Eric Rondeau 1, 3
Affiliation  

Acute tubular necrosis (ATN), a frequent histopathological feature in the early post–renal transplant biopsy, affects long‐term graft function. Appropriate markers to identify patients at risk of no or incomplete recovery after delayed graft function are lacking. In this study, we first included 41 renal transplant patients whose biopsy for cause during the first month after transplantation showed ATN lesions. Using partial microvasculature endothelial (fascin, vimentin) and tubular epithelial (vimentin) to mesenchymal transition markers, detected by immunohistochemistry, we found a significant association between partial endothelial to mesenchymal transition and poor graft function recovery (Spearman's rho = −0.55, P = .0005). Transforming growth factor–β1 was strongly expressed in these phenotypic changed endothelial cells. Extent of ATN was also correlated with short‐ and long‐term graft dysfunction. However, the association of extensive ATN with long‐term graft dysfunction (24 months posttransplant) was observed only in patients with partial endothelial to mesenchymal transition marker expression in their grafts (Spearman's rho = −0.64, P = .003), but not in those without. The association of partial endothelial to mesenchymal transition with worse renal graft outcome was confirmed on 34 other early biopsies with ATN from a second transplant center. Our results suggest that endothelial cell activation at the early phase of renal transplantation plays a detrimental role.

中文翻译:

伴有急性肾小管坏死的移植后早期活检中的微血管部分内皮间质转化可识别恢复不良的肾同种异体移植物。

急性肾小管坏死 (ATN) 是肾移植后早期活检中常见的组织病理学特征,会影响移植物的长期功能。缺乏适当的标志物来识别移植物功能延迟后无法恢复或恢复不完全的风险患者。在这项研究中,我们首先纳入了 41 名肾移植患者,这些患者在移植后第一个月的病因活检显示 ATN 病变。使用部分微血管内皮(肌束蛋白、波形蛋白)和肾小管上皮(波形蛋白)到间充质转化标记物,通过免疫组织化学检测,我们发现部分内皮到间充质转化与移植物功能恢复不良之间存在显着关联(Spearman's rho = -0.55,P =.0005)。转化生长因子-β1 在这些表型改变的内皮细胞中强烈表达。ATN 的范围也与短期和长期移植物功能障碍相关。然而,广泛的 ATN 与长期移植物功能障碍(移植后 24 个月)的相关性仅在其移植物中部分内皮至间充质转化标志物表达的患者中观察到(Spearman's rho = -0.64,P  = .003),但在那些没有。来自第二个移植中心的其他 34 个 ATN 早期活检证实了部分内皮细胞向间质细胞转化与较差肾移植结果的关联。我们的结果表明,肾移植早期的内皮细胞活化起着有害作用。
更新日期:2020-03-13
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