急性肾损伤导致远隔器官功能障碍的机制

Mechanism of acute kidney injury' s causing other distant organs dysfunction

急性肾损伤(AKI)患者有较高的死亡率。研究显示这种高死亡率与AKI患者并发的肺、心脏、肝脏以及神经系统功能衰竭密切相关。越来越多证据显示,AKI通过产生系统性炎症反应导致机体其他器官功能障碍。这一过程包括:AKI产生肾脏局部炎症信号分子;通过激活嘌呤代谢途径使血尿酸增高,放大炎症反应信号,进一步通过Toll样受体引发第二波炎症级联反应(包括细胞因子、趋化因子、炎症以及抗炎因子的释放);最后形成持续性、系统性炎症反应[以高迁移率旋蛋白1(HMGB1)释放入血为代表]。同时伴随氧化应激损伤、凋亡途径的活化以及白细胞迁移等,最终导致肺、心脏、肝脏以及神经系统功能障碍。本文综述了目前国际上最新的关于AKI及其导致远隔器官损伤作用的临床和实验研究。以便临床工作者更加深入的了解AKI导致远隔器官损伤的病理生理过程,为降低AKI患者的死亡率提供合理的治疗靶点。

Acute kidney injury （AKI） is associated with a higher mortality. Some studies have shown that the high mortality of AKI patients is closely related with dysfunction of other organs such as lungs, heart, liver, and nervous system. At present, growing evidence indicates that AKI induces other organs dysfunction by systemic inflammation. Identified pathways include： renal local inflammation; blood uric acid increasing through activation of purine metabolic pathway to amplify the inflammatory response signal resulting in a secondary wave of inflammatory cascade by Toll-like receptors （ including release of eytokines, chemokines, and inflammatory and anti-inflammatory factors, etc. ） ; and finally the formation of systemic inflammatory response （taking HMGB1 release into the blood as the representative）, which are accompanied by oxidative stress, apoptosis pathway activation, and migration of white blood cells, eventually leading to dysfunction of lungs, heart, liver, and nervous system. This paper has reviewed the latest clinical and experimental studies about AKI and its role in causing injury to distant organs, which will help clinicians to better understand AKI pathophysiological processes leading to the distant organ injury, in order to provide reasonable therapeutic targets for reducing mortality of patients with AKI.