Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, Agrigento, Italy.
Blood Purif. 2017;44(4):314-326. doi: 10.1159/000480424. Epub 2017 Nov 22.
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells. These molecules are responsible for cellular apoptosis, autophagy, cell cycle arrest, and microRNAs activation. Therefore, the early identification of sepsis-associated acute kidney injury and heart dysfunction may improve the patient clinical outcome. In this report, we will consider the role of endotoxin in the pathogenesis of sepsis, its effects on both cardiac and renal functions, and the interactions between these 2 systems in the setting of cardiorenal syndromes (CRS), particularly in CRS type 5. Finally, we will discuss the possible role of extracorporeal therapies in reducing endotoxin levels.
革兰氏阴性菌败血症是危重病患者发病率和死亡率的主要原因。分子生物学和信号通路方面的最新发现增强了我们对其发病机制的理解,并为创新治疗方法开辟了机会。内毒素在革兰氏阴性菌败血症多器官功能障碍的发病机制中起着关键作用。事实上,心脏和肾脏损伤似乎是由内毒素与免疫细胞相互作用引发的循环促炎和促凋亡介质的释放引起的。这些分子负责细胞凋亡、自噬、细胞周期停滞和 microRNAs 的激活。因此,早期识别脓毒症相关性急性肾损伤和心功能障碍可能会改善患者的临床结局。在本报告中,我们将考虑内毒素在败血症发病机制中的作用,及其对心脏和肾脏功能的影响,以及这两个系统在心脏肾脏综合征(CRS),特别是在 CRS 5 型中的相互作用。最后,我们将讨论体外治疗在降低内毒素水平方面的可能作用。