Toro Juan, Manrique-Caballero Carlos L, Gómez Hernando
Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Clin Med. 2021 Sep 16;10(18):4184. doi: 10.3390/jcm10184184.
Acute kidney injury (AKI) is a frequent complication of sepsis that increases mortality and the risk of progression to chronic kidney disease. However, the mechanisms leading to sepsis-associated AKI are still poorly understood. The recognition that sepsis induces organ dysfunction in the absence of overt necrosis or apoptosis has led to the consideration that tubular epithelial cells (TEC) may deploy defense mechanisms to survive the insult. This concept dovetails well with the notion that the defense against infection does not only depend on the capacity of the immune system to limit the microbial load (known as resistance), but also on the capacity of cells and tissues to limit tissue injury (known as tolerance). In this review, we discuss the importance of TEC metabolic reprogramming as a defense strategy during sepsis, and how this cellular response is likely to operate through a tolerance mechanism. We discuss the fundamental role of specific regulatory nodes and of mitochondria in orchestrating this response, and how this opens avenues for the exploration of targeted therapeutic strategies to prevent or treat sepsis-associated AKI.
急性肾损伤（AKI）是脓毒症常见的并发症，会增加死亡率以及进展为慢性肾病的风险。然而，导致脓毒症相关性AKI的机制仍未完全明确。脓毒症在无明显坏死或凋亡的情况下即可诱发器官功能障碍，这一认识使得人们开始考虑肾小管上皮细胞（TEC）可能会启动防御机制以在损伤中存活。这一概念与以下观点高度契合，即抗感染不仅取决于免疫系统限制微生物负荷的能力（即抵抗力），还取决于细胞和组织限制组织损伤的能力（即耐受性）。在本综述中，我们讨论了TEC代谢重编程作为脓毒症期间防御策略的重要性，以及这种细胞反应可能如何通过耐受机制发挥作用。我们还讨论了特定调控节点和线粒体在协调这种反应中的基本作用，以及这如何为探索预防或治疗脓毒症相关性AKI的靶向治疗策略开辟道路。
