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人血清白蛋白与尿毒症毒素的相互作用:针对尿毒症毒素清除的新策略需求

Interaction of Human Serum Albumin with Uremic Toxins: The Need of New Strategies Aiming at Uremic Toxins Removal.

作者信息

Zare Fahimeh, Janeca Adriana, Jokar Seyyed M, Faria Mónica, Gonçalves Maria Clara

机构信息

Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal.

Centro de Química Estrutural (CQE), 1049-001 Lisboa, Portugal.

出版信息

Membranes (Basel). 2022 Feb 25;12(3):261. doi: 10.3390/membranes12030261.

Abstract

Chronic kidney disease (CKD) is acknowledged worldwide to be a grave threat to public health, with the number of US end-stage kidney disease (ESKD) patients increasing steeply from 10,000 in 1973 to 703,243 in 2015. Protein-bound uremic toxins (PBUTs) are excreted by renal tubular secretion in healthy humans, but hardly removed by traditional haemodialysis (HD) in ESKD patients. The accumulation of these toxins is a major contributor to these sufferers' morbidity and mortality. As a result, some improvements to dialytic removal have been proposed, each with their own upsides and drawbacks. Longer dialysis sessions and hemodiafiltration, though, have not performed especially well, while larger dialyzers, coupled with a higher dialysate flow, proved to have some efficiency in indoxyl sulfate (IS) clearance, but with reduced impact on patients' quality of life. More efficient in removing PBUTs was fractionated plasma separation and adsorption, but the risk of occlusive thrombosis was worryingly high. A promising technique for the removal of PBUTs is binding competition, which holds great hopes for future HD. This short review starts by presenting the PBUTs chemistry with emphasis on the chemical interactions with the transport protein, human serum albumin (HSA). Recent membrane-based strategies targeting PBUTs removal are also presented, and their efficiency is discussed.

摘要

慢性肾脏病(CKD)在全球范围内被公认为对公众健康的严重威胁,美国终末期肾病(ESKD)患者数量从1973年的10,000人急剧增加到2015年的703,243人。在健康人体内,蛋白结合尿毒症毒素(PBUTs)通过肾小管分泌排出,但在ESKD患者中,传统血液透析(HD)几乎无法清除这些毒素。这些毒素的积累是导致这些患者发病和死亡的主要因素。因此,有人提出了一些改进透析清除的方法,每种方法都有其优缺点。然而,延长透析时间和血液透析滤过的效果并不特别理想,而更大的透析器加上更高的透析液流量,在清除硫酸吲哚酚(IS)方面证明有一定效率,但对患者生活质量的影响较小。在清除PBUTs方面更有效的是分步血浆分离和吸附,但闭塞性血栓形成的风险高得令人担忧。一种有前景的清除PBUTs的技术是结合竞争,这为未来的血液透析带来了很大希望。这篇简短的综述首先介绍PBUTs的化学性质,重点是与转运蛋白人血清白蛋白(HSA)的化学相互作用。还介绍了最近针对清除PBUTs的基于膜的策略,并讨论了它们的效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ab/8953794/89e202a2b9c8/membranes-12-00261-g001.jpg

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