肾性贫血治疗中罗沙司他的临床运用研究

Clinical application of Roxadustat in the treatment of renal anemia

肾性贫血为慢性肾脏病常见的并发症,其严重程度以及患病率会随着肾功能的进展而逐渐增加。若贫血得不到有效的控制,会对患者的生活质量、生存率带来显著负面影响,且提升死亡与心血管疾病发生风险。目前临床上主要治疗肾性贫血的药物为促红细胞生长素(erythropoietin,EPO)类似物及铁剂,上述2种药物有可能导致心血管疾病、高血压、氧化应激、过敏反应等并发症,临床使用受限。少部分患者即使大剂量使用促红素,也难以改善其贫血状态。罗沙司他胶囊是目前临床上用于治疗慢性肾脏病合并肾性贫血的口服药,该药通过模拟脯氨酰羟化酶(prolyl hydroxylase,PH)的底物之一酮戊二酸来抑制PH酶,使得低氧诱导因子稳定性得到控制,并强化促红细胞生成素及其受体(EPO receptor,EPOR)表达,进而改善机体铁代谢,有助于红细胞生成。罗沙司他的给药途径方便,可提升患者治疗意愿,提升临床肾性贫血的治疗达标率。目前国内外已经完成罗沙司他Ⅲ期临床试验,但广大临床医师缺乏对罗沙司他的长期用药经验。研究结合大量文献,综合上级医院专科教授临床经验分享,以及罗沙司他胶囊的临床应用实际情况,对罗沙司他在药理机制、临床研究方面进行归纳,供临床专科医师参考。

Renal anemia is one of the main complications of chronic kidney disease,and its prevalence and severity gradually increase with the progression of renal function.If anemia is not well controlled,it seriously affects the survival rate and quality of life of patients,increases the incidence of cardiovascular events and the risk of death.At present,the main drugs for the treatment of renal anemia are erythropoietin(EPO)analogues and iron.The above two drugs may have complications such as cardiovascular disease,hypertension,oxidative stress,allergic reaction and so on,which limits the clinical use.There are still a small number of patients,even if a large dose of erythropoietin is used,it is difficult to correct their anemia.Roxadustat capsule is currently the first oral drug for the treatment of chronic kidney disease complicated with renal anemia.The drug inhibits pH enzyme by simulating ketoglutarate,one of the substrates of prolyl hydroxylase(PH),so as to control the stability of hypoxia inducible factors,strengthen the expression of erythropoietin and its receptor(EPOR),improve iron metabolism and contribute to erythropoiesis.The administration route of Roxadustat is convenient,which improves the treatment willingness of patients and improves the standard rate of renal anemia in clinic.At present,phaseⅢclinical trials have been completed at home and abroad.For the majority of clinicians,they lack long-term drug use experience.The author consulted a large number of literatures,shared the clinical experience of specialized professors in higher-level hospitals,and summarized the pharmacological mechanism and clinical research of roxasta capsule in combination with the actual clinical application of roxasta capsule for the reference of clinical specialists.