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慢性肾脏病中的贫血:从病理生理学到当前治疗方法,再到未来治疗药物

Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents.

作者信息

Portolés Jose, Martín Leyre, Broseta José Jesús, Cases Aleix

机构信息

Department of Nephrology, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain.

Anemia Working Group Spanish Society of Nephrology, Madrid, Spain.

出版信息

Front Med (Lausanne). 2021 Mar 26;8:642296. doi: 10.3389/fmed.2021.642296. eCollection 2021.

DOI:10.3389/fmed.2021.642296
PMID:33842503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8032930/
Abstract

Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and an increased morbidity and mortality. The mechanisms involved in anemia associated to CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Patients are most commonly managed with oral or intravenous iron supplements and with erythropoiesis stimulating agents (ESA). However, these treatments have associated risks, and sometimes are insufficiently effective. Nonetheless, in the last years, there have been some remarkable advances in the treatment of CKD-related anemia, which have raised great expectations. On the one hand, a novel family of drugs has been developed: the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). These agents induce, among other effects, an increase in the production of endogenous EPO, improve iron availability and reduce hepcidin levels. Some of them have already received marketing authorization. On the other hand, recent clinical trials have elucidated important aspects of iron supplementation, which may change the treatment targets in the future. This article reviews the current knowledge of the pathophysiology CKD-related anemia, current and future therapies, the trends in patient management and the unmet goals.

摘要

贫血是慢性肾脏病(CKD)的常见并发症,与生活质量下降、发病率和死亡率增加相关。CKD相关性贫血涉及的机制多样且复杂。这些机制包括内源性促红细胞生成素(EPO)生成减少、绝对和/或功能性缺铁以及铁调素水平升高引起的炎症等。患者最常接受口服或静脉铁剂补充以及促红细胞生成刺激剂(ESA)治疗。然而,这些治疗存在相关风险,有时效果也不充分。尽管如此,近年来,CKD相关性贫血的治疗取得了一些显著进展,引发了人们极大的期望。一方面,开发了一类新型药物:缺氧诱导因子脯氨酰羟化酶抑制剂(HIF-PHIs)。这些药物除其他作用外,还能增加内源性EPO的生成,提高铁的利用率并降低铁调素水平。其中一些药物已获得上市许可。另一方面,近期的临床试验阐明了铁剂补充的重要方面,这可能会改变未来的治疗目标。本文综述了CKD相关性贫血病理生理学的现有知识、当前和未来的治疗方法、患者管理趋势以及尚未实现的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/8032930/96682745005d/fmed-08-642296-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/8032930/35d106b1d3cb/fmed-08-642296-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/8032930/96682745005d/fmed-08-642296-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/8032930/35d106b1d3cb/fmed-08-642296-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adeb/8032930/96682745005d/fmed-08-642296-g0002.jpg

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Iron replacement therapy in the management of anaemia in non-dialysis Chronic kidney disease patients: Perspective of the Spanish Nephrology Society Anaemia Group.非透析慢性肾脏病患者贫血管理中的铁剂替代疗法:西班牙肾脏病学会贫血小组的观点
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