Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Toxins (Basel). 2022 Jun 11;14(6):402. doi: 10.3390/toxins14060402.
In patients with severe kidney disease, renal clearance is compromised, resulting in the accumulation of a plethora of endogenous waste molecules that cannot be removed by current dialysis techniques, the most often applied treatment. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds of which many are too large to be filtered and/or are protein-bound. Their renal excretion depends largely on renal tubular secretion, by which the binding is shifted towards the free fraction that can be eliminated. To facilitate this process, kidney proximal tubule cells are equipped with a range of transport proteins that cooperate in cellular uptake and urinary excretion. In recent years, innovations in dialysis techniques to advance uremic toxin removal, as well as treatments with drugs and/or dietary supplements that limit uremic toxin production, have provided some clinical improvements or are still in progress. This review gives an overview of these developments. Furthermore, the role protein-bound uremic toxins play in inter-organ communication, in particular between the gut (the side where toxins are produced) and the kidney (the side of their removal), is discussed.
在严重肾病患者中，肾脏清除功能受损，导致大量内源性废物分子积聚，而目前的透析技术无法清除这些物质，这些技术是最常用的治疗方法。这些尿毒症潴留溶质，也称为尿毒症毒素，是一组异质的有机化合物，其中许多物质太大而无法被过滤和/或与蛋白质结合。它们的肾脏排泄主要依赖于肾小管分泌，通过这种分泌，结合物会转移到可以被清除的游离部分。为了促进这个过程，肾脏近端小管细胞配备了一系列转运蛋白，这些蛋白在细胞摄取和尿液排泄中相互协作。近年来，透析技术的创新以提高尿毒症毒素的清除率，以及使用药物和/或膳食补充剂来限制尿毒症毒素的产生，已经提供了一些临床改善，或者仍在进行中。这篇综述概述了这些进展。此外，还讨论了蛋白结合尿毒症毒素在器官间通讯中的作用，特别是在肠道（毒素产生的部位）和肾脏（毒素清除的部位）之间的作用。
