a Department of Nephrology and Dialysis , A. Manzoni Hospital , Lecco , Italy.
Expert Opin Investig Drugs. 2018 Jul;27(7):613-621. doi: 10.1080/13543784.2018.1493455. Epub 2018 Jul 12.
In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive.
We searched PubMed for original articles, reviews, and editorials having as a topic anemia, CKD, hypoxia inducible factor, hepcidin, iron, and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). HIF-PHI are a new class of small molecules activating HIF-alfa isoforms (the main mediators of the effects of hypoxia on the body). This causes the secretion of endogenous erythropoietin and increased iron availability. Differing from ESA, HIF-PHI are administered orally. Preliminary data from phase-II clinical studies have shown their efficacy and safety in the short term.
HIF-PHI are a new promising class of drugs. The results of large, phase-III clinical studies are awaited to prove their efficacy and safety on cardiovascular events and cancer development in the long term. Their capability of penetrating the ESA market in the future will be influenced also by their selling price. The oral administration of HIF-PHI will be weighed to the 'intra-lines' infusion of ESA in hemodialysis or to the infrequent subcutaneous injections of long-acting ESA.
在过去十年中，人们对慢性肾脏病 (CKD) 患者使用红细胞生成刺激剂 (ESA) 和静脉铁剂的情况表示担忧，尤其是在高剂量使用时。此外，ESA 的治疗费用昂贵。
我们在 PubMed 上搜索了以贫血、CKD、缺氧诱导因子、铁调素、缺氧诱导因子脯氨酰羟化酶抑制剂 (HIF-PHI) 为主题的原创文章、综述和社论。HIF-PHI 是一类新型小分子药物，可激活 HIF-α 同工型（缺氧对机体影响的主要介质）。这会导致内源性促红细胞生成素的分泌和铁的可用性增加。与 ESA 不同，HIF-PHI 可口服给药。II 期临床研究的初步数据显示了它们在短期内的疗效和安全性。
HIF-PHI 是一类有前途的新型药物。需要等待大型 III 期临床研究的结果，以证明它们在长期内对心血管事件和癌症发展的疗效和安全性。它们在未来渗透 ESA 市场的能力还将受到其销售价格的影响。HIF-PHI 的口服给药将与血液透析中的 ESA 线内输注或长效 ESA 的低频皮下注射进行权衡。
