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慢性肾脏病相关性贫血:新的治疗方法。

Chronic kidney disease-associated anemia: new remedies.

作者信息

Del Vecchio Lucia, Cavalli Andrea, Tucci Benedetta, Locatelli Francesco

机构信息

A Manzoni Hospital, Department of Nephrology, Dialysis and Renal Transplant, Via dell'Eremo 9, 23900 Lecco, Italy.

出版信息

Curr Opin Investig Drugs. 2010 Sep;11(9):1030-8.

Abstract

Erythropoiesis stimulating agents (ESAs) are effective drugs that correct anemia in patients with chronic kidney disease (CKD). Recombinant human erythropoietin (EPO), the first ESA that became available more than 20 years ago, is similar to the naturally occurring molecule. In subsequent years, pharmacological research focused on the development of new agents with improved characteristics, with the creation of high molecular weight ESAs having been the first approach. In more recent years, new agents have been developed, including peginesatide (Hematide; Affymax Inc/Takeda Pharmaceutical Co Ltd), which is a dimeric peptide with a chemical structure unrelated to EPO that is being evaluated in phase III clinical trials. In addition, the clinical development of two inhibitors of hypoxia-inducible transcription factor has been resumed recently, while other approaches, such as gene therapy and EPO fusion proteins, and the inhibition of GATA and hematopoietic cell phosphatase remain far from being applicable in clinical practice. New iron compounds, which are becoming increasingly available, will facilitate an integrated approach to anemia management using both iron and/or ESAs, according to the clinical needs of patients. This review discusses new therapeutic options (already available or still under development) for the treatment of CKD-associated anemia, including ESAs and intravenous iron molecules.

摘要

促红细胞生成素(ESAs)是纠正慢性肾脏病(CKD)患者贫血的有效药物。重组人促红细胞生成素(EPO)是20多年前问世的首个ESAs,与天然存在的分子相似。在随后的几年里,药理学研究集中在开发具有改进特性的新药物上,开发高分子量ESAs是首要方法。近年来,已开发出新型药物,包括培加尼肽(Hematide;Affymax公司/武田制药有限公司),这是一种化学结构与EPO无关的二聚体肽,正在进行III期临床试验评估。此外,两种缺氧诱导转录因子抑制剂的临床开发最近已恢复,而其他方法,如基因治疗和EPO融合蛋白,以及对GATA和造血细胞磷酸酶的抑制,距离临床应用仍很遥远。越来越多的新型铁化合物将根据患者的临床需求,促进采用铁剂和/或ESAs的综合方法来管理贫血。本综述讨论了治疗CKD相关性贫血的新治疗选择(已上市或仍在研发中),包括ESAs和静脉铁剂分子。

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