Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure.
Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure.
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血管生成素-2的表现优于其他与严重的脓毒症和呼吸衰竭患者严重急性肾脏损伤相关的内皮生物标志物。
DOI：
10.1186/s13054-021-03474-z
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发表时间：
2021-02-04
期刊：
影响因子：
--
通讯作者：
Ware LB
中科院分区：
文献类型：
--
作者：
Yu WK;McNeil JB;Wickersham NE;Shaver CM;Bastarache JA;Ware LB
内皮功能障碍和损伤是脓毒症的主要病理生理特征。脓毒症也是危重患者急性肾损伤(AKI)最常见的原因。虽然大多数AKI在脓毒症中的研究都集中在肾小管上皮损伤上，但对内皮功能障碍和损伤的作用研究较少。这项研究的目的是首先调查脓毒症患者的内皮功能障碍和损伤生物标志物是否与严重的AKI相关。第二个目标是确定对严重AKI最有效的生物标记物，以及该生物标记物是否与不同败血症病因和临床结果的严重AKI有关。我们研究了参加前瞻性观察验证急性肺损伤标志物诊断(有效)研究的严重脓毒症和急性呼吸衰竭(ARF)的成人。在研究登记时，检测血浆内皮细胞功能障碍和损伤生物标志物，包括血管生成素-2、可溶性血管内皮钙粘素(sve-cadherin)、内毒素和syndecan-1。初步分析集中于内皮生物标记物水平与严重AKI(定义为肾脏疾病：改善全球预后[KDIGO]AKI阶段2或3)、其他器官功能障碍(由布鲁塞尔器官衰竭评分定义)以及肺性和非肺性脓毒症的比较。在入选的228名脓毒症患者中，141人发展为严重AKI。严重AKI的脓毒症患者的血浆血管生成素-2、内毒素、sVE-钙粘素和Syndecan-1水平显著高于无严重AKI的患者。在四种血管内皮细胞生物标志物中，只有血管生成素-2与重度急性脑梗塞独立相关(优势比为6.07Plog递增，95%可信区间为2.34~15.78，p <； 为0.001)。有肝、凝血和循环衰竭的脓毒症患者血浆血管生成素-2水平按四分位数显著升高。非肺脓毒症患者的血浆血管生成素-2水平也显著高于肺脓毒症患者。在内皮功能障碍和损伤的四个生物标志物中，血管生成素-2与严重脓毒症和ARF患者发生严重AKI的独立相关性最强。血浆血管生成素-2水平也与其他器官功能障碍、非肺脓毒症和死亡有关。这些发现强调了早期内皮功能障碍和损伤在脓毒症诱导的AKI发病机制中的重要性。
Endothelial dysfunction and injury is a major pathophysiologic feature of sepsis. Sepsis is also the most frequent cause of acute kidney injury (AKI) in critically ill patients. Though most studies of AKI in sepsis have focused on tubular epithelial injury, the role of endothelial dysfunction and injury is less well studied. The goal of this study was first to investigate whether endothelial dysfunction and injury biomarkers were associated with severe AKI in sepsis patients. The second goal was to determine the best performing biomarker for severe AKI and whether this biomarker was associated with severe AKI across different etiologies of sepsis and clinical outcomes. We studied adults with severe sepsis and acute respiratory failure (ARF) enrolled in the prospective observational Validating Acute Lung Injury markers for Diagnosis (VALID) study. Plasma endothelial dysfunction and injury biomarkers, including angiopoietin-2, soluble vascular endothelial cadherin (sVE-cadherin), endocan and syndecan-1, were measured at study enrollment. Primary analysis focused on the association between endothelial biomarker levels with severe AKI (defined as Kidney Disease: Improving Global Outcomes [KDIGO] AKI stage 2 or 3), other organ dysfunctions (defined by Brussels organ failure scores), and comparison of pulmonary versus non-pulmonary sepsis. Among 228 sepsis patients enrolled, 141 developed severe AKI. Plasma levels of angiopoietin-2, endocan, sVE-cadherin, and syndecan-1 were significantly higher in sepsis patients with severe AKI compared to those without severe AKI. Among four endothelial biomarkers, only angiopoietin-2 was independently associated with severe AKI (odds ratio 6.07 per log increase, 95% CI 2.34–15.78, p < 0.001). Plasma angiopoietin-2 levels by quartile were significantly higher in sepsis patients with hepatic, coagulation, and circulatory failure. Plasma angiopoietin-2 levels were also significantly higher in patients with non-pulmonary sepsis compared to subjects with pulmonary sepsis. Among four biomarkers of endothelial dysfunction and injury, angiopoietin-2 had the most robust independent association with development of severe AKI in patients with severe sepsis and ARF. Plasma angiopoietin-2 levels were also associated with other organ dysfunctions, non-pulmonary sepsis, and death. These findings highlight the importance of early endothelial dysfunction and injury in the pathogenesis of sepsis-induced AKI.
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影响因子：
8.8
作者：
David S;Mukherjee A;Ghosh CC;Yano M;Khankin EV;Wenger JB;Karumanchi SA;Shapiro NI;Parikh SM
通讯作者：
Parikh SM
影响因子：
8.8
作者：
Levy, MM;Fink, MP;Ramsay, G
通讯作者：
Ramsay, G
影响因子：
6.9
作者：
Araujo, Camila Barbosa;de Oliveira Neves, Fernanda Macedo;Liborio, Alexandre Braga
通讯作者：
Liborio, Alexandre Braga
DOI：
10.1164/rccm.201208-1460oc
发表时间：
2013-04-01
影响因子：
24.7
作者：
Agrawal, Ashish;Matthay, Michael A.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.
DOI：
10.1186/s13054-018-2222-7
发表时间：
2018-10-26
期刊：
Critical care (London, England)
影响因子：
--
作者：
De Freitas Caires N;Gaudet A;Portier L;Tsicopoulos A;Mathieu D;Lassalle P
通讯作者：
Lassalle P