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Abstract：
Acute kidney injury (AKI) is a common consequence of sepsis with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex and involves several mechanisms leading to exacerbated inflammatory response associated with renal injury. A large body of evidence suggests that inflammation is tightly linked to AKI through bidirectional interaction between renal and immune cells. Preclinical data from our and other laboratories have identified in complement system activation a crucial mediator of AKI. Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate the progression of preexisting chronic kidney disease. Recent findings have revealed striking morphological and functional changes in renal parenchymal cells induced by mitochondrial dysfunction, cell cycle arrest via the activation of signaling pathways involved in aging process, microvascular rarefaction, and early fibrosis. Although major advances have been made in our understanding of the pathophysiology of AKI, there are no available preventive and therapeutic strategies in this field. The identification of ideal clinical biomarkers for AKI enables prompt and effective therapeutic strategy that could prevent the progression of renal injury and promote repair process. Therefore, the use of novel biomarkers associated with clinical and functional criteria could provide early interventions and better outcome. Several new drugs for AKI are currently being investigated; however, the complexity of this disease might explain the failure of pharmacological intervention targeting just one of the many systems involved. The hypothesis that blood purification could improve the outcome of septic AKI has attracted much attention. New relevant findings on the role of polymethylmethacrylate-based continuous veno-venous hemofiltration in septic AKI have been reported. Herein, we provide a comprehensive literature review on advances in the pathophysiology of septic AKI and potential therapeutic approaches in this field.
摘要：
急性肾损伤（AKI）是脓毒症的常见后果，死亡率高达40％。脓毒性AKI的发病机制是复杂的，涉及导致与肾损伤相关的炎症反应加剧的几种机制。大量证据表明，炎症通过肾脏和免疫细胞之间的双向相互作用与AKI紧密相关。来自我们和其他实验室的临床前数据已经在补体系统激活中确定了AKI的关键介质。AKI后的部分恢复可能导致长期后果，从而导致慢性功能障碍，并且还可能加速先前存在的慢性肾脏疾病的进展。最近的发现揭示了线粒体功能障碍引起的肾实质细胞的显著形态和功能变化。细胞周期阻滞通过激活参与衰老过程的信号通路，微血管稀疏,和早期纤维化。尽管我们对AKI病理生理学的理解取得了重大进展，在这一领域没有可用的预防和治疗策略.AKI的理想临床生物标志物的鉴定能够实现及时有效的治疗策略，可以预防肾损伤的进展并促进修复过程。因此,使用与临床和功能标准相关的新型生物标志物可以提供早期干预和更好的结局.目前正在研究几种治疗AKI的新药；然而，这种疾病的复杂性可能解释了仅针对所涉及的众多系统之一的药物干预的失败。血液净化可改善脓毒性AKI预后的假说备受关注。已经报道了关于基于聚甲基丙烯酸甲酯的连续静脉-静脉血液滤过在脓毒性AKI中的作用的新相关发现。在这里，我们提供了关于脓毒症AKI病理生理学进展和该领域潜在治疗方法的综合文献综述.
