Sepsis-induced acute kidney injury.
Sepsis-induced acute kidney injury.
复制标题
DOI：
10.1097/mcc.0000000000000356
复制
发表时间：
2016-12
影响因子：
3.3
通讯作者：
Kellum JA
中科院分区：
文献类型：
--
作者：
Gómez H;Kellum JA
脓毒症是一种常见且经常致命的疾病，其中死亡率一直与器官功能障碍增加有关。例如，急性肾损伤（阿基）发生在40-50%的脓毒症患者中，并使死亡率增加6至8倍。然而，脓毒症引起器官功能障碍的机制还不清楚，因此目前的治疗仍然是反应性和非特异性的。最近的研究已经挑战了先前的观念，即器官功能障碍仅继发于灌注不足，例如，通过显示阿基发生在正常或增加的肾血流量的情况下;并且其特征不是急性肾小管坏死或凋亡，而是共定位的缓慢肾小管周血流量和肾小管上皮细胞氧化应激的异质区域。证据还表明，微血管功能障碍、炎症和对炎性损伤的代谢反应是可以解释脓毒症诱导的阿基发展的基本病理生理机制。这些发现的意义是重要的，因为在该领域数十年的负面临床试验的背景下，认识到其他机制在发挥作用，打开了更好地了解损伤和修复过程的可能性，并提供了一个宝贵的机会，设计机制靶向治疗干预措施。
Sepsis is a common and frequently fatal condition in which mortality has been consistently linked to increasing organ dysfunction. For example, acute kidney injury (AKI) occurs in 40–50% of septic patients and increases mortality six to eight-fold. However, the mechanisms by which sepsis causes organ dysfunction are not well understood and hence current therapy remains reactive and nonspecific. Recent studies have challenged the previous notion that organ dysfunction is solely secondary to hypoperfusion, by showing, for example, that AKI occurs in the setting of normal or increased renal blood flow; and that it is characterized not by acute tubular necrosis or apoptosis, but rather by heterogeneous areas of colocalized sluggish peritubular blood flow and tubular epithelial cell oxidative stress. Evidence has also shown that microvascular dysfunction, inflammation, and the metabolic response to inflammatory injury are fundamental pathophysiologic mechanisms that may explain the development of sepsis-induced AKI. The implications of these findings are significant because in the context of decades of negative clinical trials in the field, the recognition that other mechanisms are at play opens the possibility to better understand the processes of injury and repair, and provides an invaluable opportunity to design mechanism-targeted therapeutic interventions.