Abstract：
UNASSIGNED: The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under hypoxic conditions has led to the development of oral drugs, HIF-Prolyl Hydroxylase inhibitors (HIF-PHIs), that constantly activate erythropoietin by inhibiting prolyl hydroxylase. HIF-PHIs have gained rapid approval in Asian countries, including Japan, with six distinct types entering clinical application.
UNASSIGNED: This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat.
UNASSIGNED: A phase 3, randomized, open-label, clinical trial (PRO2TECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNO2VATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies.
UNASSIGNED: This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat.
UNASSIGNED: A phase 3, randomized, open-label, clinical trial (PRO2TECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNO2VATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies.
摘要：
■1990年代促红细胞生成素刺激剂的突破改善了慢性肾脏病患者和肾性贫血并发症的预后和治疗。低氧诱导因子(HIF)转录因子在低氧条件下的新分子机制的发现导致了口服药物的发展。HIF-丙氨酰羟化酶抑制剂（HIF-PHIs），不断激活促红细胞生成素通过抑制脯氨酸羟化酶。HIF-PHI在亚洲国家获得了迅速的批准，包括日本,有六种不同的类型进入临床应用。
■本文提供了对最新文献的全面回顾，特别关注vadadustat的有效性和安全性。
■第三阶段，随机，开放标签，临床试验(PRO2TECT)表明,在先前未接受ESA治疗的非透析依赖患者中,与darbepoetinalfa相比,vadadustat在血液学疗效方面具有预设的非劣效性.然而,在非美国/非欧洲患者中，vadadustat在主要不良心血管事件中未显示非劣效性。部分原因可能是这些国家eGFR基线水平的不平衡。在透析依赖患者中，一项3期临床试验(INNO2VATE)显示,vadadustat在心血管安全性和血红蛋白水平维持方面不劣于darbepoietinalfa.不良事件包括癌症，视网膜病变,血栓形成,血管钙化应在未来的临床研究中进行评估。
■本文提供了对最新文献的全面回顾，特别关注vadadustat的有效性和安全性。
■第三阶段，随机，开放标签，临床试验(PRO2TECT)表明,在先前未接受ESA治疗的非透析依赖患者中,与darbepoetinalfa相比,vadadustat在血液学疗效方面具有预设的非劣效性.然而,在非美国/非欧洲患者中，vadadustat在主要不良心血管事件中未显示非劣效性。部分原因可能是这些国家eGFR基线水平的不平衡。在透析依赖患者中，一项3期临床试验(INNO2VATE)显示,vadadustat在心血管安全性和血红蛋白水平维持方面不劣于darbepoietinalfa.不良事件包括癌症，视网膜病变,血栓形成,血管钙化应在未来的临床研究中进行评估。
