低氧诱导因子脯氨酰羟化酶抑制剂罗沙司他临床应用若干问题

    Issues on clinical application of hypoxia-inducible factor prolyl hydroxylase inhibitor Roxadustat

    • 摘要: 肾性贫血是慢性肾脏病的重要临床表现,促红细胞生成素(erythropoietin,EPO)的相对或绝对缺乏是肾性贫血的最主要原因。目前肾性贫血的治疗主要是EPO类似物联合铁剂替代输血,但因其副作用,临床使用受限。低氧诱导因子是调控EPO基因表达的转录因子,而脯氨酰羟化酶是调节低氧诱导因子降解的限速酶。脯氨酰羟化酶抑制剂能够稳定低氧诱导因子而促进EPO表达。罗沙司他(Roxadustat)作为全球首个低氧诱导因子-脯氨酰羟化酶抑制剂率先完成了Ⅲ期临床试验,并在中国获批上市。目前的用药经验大部分来自于我国的Ⅲ期临床试验。因此,对于广大临床医生来说,缺乏长期用药经验。本文结合目前临床实际情况,对该药在临床应用过程中的若干问题简要归纳如下,以供临床医生参考。

       

      Abstract: Renal anemia is an important clinical manifestation of chronic kidney disease.The relative or absolute deficiency of erythropoietin (EPO) is the main cause of renal anemia.At present,renal anemia is treated mainly with EPO analogues combined with ferralia.However,its clinical application is limited due to its side effects.Hypoxia-inducible factor (HIF) is a transcription factor regulating EPO gene expression.Prolyl hydroxylase is the rate limiting enzyme that regulates the degradation of HIF.Prolyl hydroxylase inhibitor (PHI) can stabilize HIF and promote EPO expression.As the first HIF-PHI in the world,roxadustat has first completed phase Ⅲ clinical trials and been approved for marketing in China.At present,most of its medication experience comes from phase Ⅲ clinical trials in China.Therefore,most clinicians lack the long-term medication experience of roxadustat.Therefore,we briefly summarize some issues on the clinical application of roxadustat in this paper for clinicians' reference.

       

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