Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Nat Rev Nephrol. 2019 May;15(5):301-316. doi: 10.1038/s41581-019-0111-1.
Uraemic syndrome (also known as uremic syndrome) in patients with advanced chronic kidney disease involves the accumulation in plasma of small-molecule uraemic solutes and uraemic toxins (also known as uremic toxins), dysfunction of multiple organs and dysbiosis of the gut microbiota. As such, uraemic syndrome can be viewed as a disease of perturbed inter-organ and inter-organism (host-microbiota) communication. Multiple biological pathways are affected, including those controlled by solute carrier (SLC) and ATP-binding cassette (ABC) transporters and drug-metabolizing enzymes, many of which are also involved in drug absorption, distribution, metabolism and elimination (ADME). The remote sensing and signalling hypothesis identifies SLC and ABC transporter-mediated communication between organs and/or between the host and gut microbiota as key to the homeostasis of metabolites, antioxidants, signalling molecules, microbiota-derived products and dietary components in body tissues and fluid compartments. Thus, this hypothesis provides a useful perspective on the pathobiology of uraemic syndrome. Pathways considered central to drug ADME might be particularly important for the body's attempts to restore homeostasis, including the correction of disturbances due to kidney injury and the accumulation of uraemic solutes and toxins. This Review discusses how the remote sensing and signalling hypothesis helps to provide a systems-level understanding of aspects of uraemia that could lead to novel approaches to its treatment.
尿毒症综合征（也称为尿毒症综合征）发生于慢性肾脏病晚期患者，涉及血浆中小分子尿毒症溶质和尿毒症毒素（也称为尿毒症毒素）的蓄积、多个器官功能障碍以及肠道微生物失调。因此，尿毒症综合征可以被视为一种涉及器官间和机体间（宿主-微生物群）通讯紊乱的疾病。多种生物学途径受到影响，包括溶质载体（SLC）和 ATP 结合盒（ABC）转运蛋白以及药物代谢酶所调控的途径，其中许多途径也参与药物的吸收、分布、代谢和消除（ADME）。远程传感和信号假说确定 SLC 和 ABC 转运蛋白介导的器官间和/或宿主与肠道微生物群间的通讯是维持代谢物、抗氧化剂、信号分子、微生物群衍生产物和膳食成分在体内组织和体液隔室中内稳态的关键。因此，该假说为尿毒症综合征的病理生物学提供了一个有用的视角。被认为对药物 ADME 起核心作用的途径可能对机体恢复内稳态的尝试特别重要，包括纠正因肾脏损伤和尿毒症溶质及毒素蓄积所致的紊乱。这篇综述讨论了远程传感和信号假说如何有助于提供对尿毒症某些方面的系统水平理解，这些理解可能为其治疗带来新方法。
