Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome
Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome
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DOI：
10.1007/s00134-009-1726-7
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发表时间：
2010-03-01
影响因子：
38.9
通讯作者：
Faulhaber-Walter, Robert
中科院分区：
文献类型：
--
作者：
Kuempers, Philipp;Hafer, Carsten;Faulhaber-Walter, Robert
内皮细胞活化是微循环功能障碍、毛细血管渗漏和多器官功能障碍综合征（MODS）发病的早期事件。血管生成素-2 （ang2）是内皮特异性Tie2受体的一种循环拮抗配体，已被确定为内皮活化的非冗余守门人。基于我们之前的报告显示Ang-2在内毒素血症和脓毒症中的释放，我们旨在研究Ang-2在重症监护病房（ICU）需要肾脏替代治疗（RRT）的患者中作为结果特异性生物标志物的实用性。我们在ICU开始RRT时，用ELISA法检测了117例AKI危重患者的循环Ang-2。在RRT开始后28天的研究期间，对死亡率、住院时间和肾脏恢复情况进行前瞻性评估。与RIFLE分类-危险的患者相比，RIFLE分类-损伤或衰竭的AKI患者循环Ang-2水平显著升高。循环ang2水平升高与氧合受损、低平均动脉压、血管加压剂剂量和序贯器官衰竭评估（SOFA）评分相关。在RRT开始后第0天和第14天，非幸存者的Ang-2浓度显著高于幸存者。多变量Cox回归和决策树分析证实了Ang-2升高作为28天生存率预测因子的独立预后影响。本研究的结果表明，循环Ang-2是ICU透析依赖性AKI患者死亡率的一个强大且独立的预测因子。
Endothelial activation has emerged as an early event in the pathogenesis of microcirculatory dysfunction, capillary leakage and multi-organ dysfunction syndrome (MODS). Angiopoietin-2 (Ang-2), a circulating antagonistic ligand of the endothelial-specific Tie2 receptor, has been identified as a non-redundant gatekeeper of endothelial activation. On the basis of our previous report demonstrating release of Ang-2 in endotoxemia and sepsis, we aimed to study the utility of Ang-2 to serve as an outcome-specific biomarker in patients requiring renal replacement therapy (RRT) in the intensive care unit (ICU).We measured circulating Ang-2 by ELISA in 117 critically ill patients with AKI at inception of RRT in the ICU. Mortality, length of stay and renal recovery were prospectively assessed during a study period of 28 days after the inception of RRT.Circulating Ang-2 levels were significantly higher in AKI patients with RIFLE category-Injury or -Failure, compared to patients with RIFLE category-Risk. Elevated levels of circulating Ang-2 correlated with impaired oxygenation, low mean arterial pressure, vasopressor dose and the sequential organ failure assessment (SOFA) score. Ang-2 concentrations were significantly higher in non-survivors than in survivors at day 0 and day 14 after initiation of RRT. Multivariate Cox regression and decision tree analyses confirmed a strong independent prognostic impact of elevated Ang-2 as a predictor of 28-day survival.The results from this study indicate that circulating Ang-2 is as a strong and independent predictor of mortality in ICU patients with dialysis-dependent AKI.