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罗沙司他治疗未接受透析的肾脏病患者的贫血
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis


Nan Chen ... 其他 • 2019.09.12
相关阅读
• 罗沙司他治疗长期透析患者的贫血 • 缺氧反应途径——向研究人员致敬

罗沙司他治疗肾性贫血

 

林善锬†*,殷立平‡

复旦大学附属华山医院肾脏病科;南京中医药大学第二附属医院肾脏科

*通讯作者

 

慢性肾脏病例在过去20多年全世界各地都有了显著增加,其患病率大多达10%左右,仅中国据统计就约有1.2亿患者。因此,本病已成为全球及我国公共卫生共同的重要问题。

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摘要


背景

罗沙司他(FG-4592)是低氧诱导因子(HIF)脯氨酰羟化酶的口服抑制剂,可刺激红细胞生成并调节铁代谢。在纳入慢性肾脏病患者的2期研究中,罗沙司他将内源性红细胞生成素水平升高至接近或达到生理范围,同时升高了血红蛋白水平并改善了铁稳态。关于在未接受透析的慢性肾脏病患者中,罗沙司他治疗贫血的疗效和安全性,我们需要更多数据。

 

方法

这是一项在中国29个研究中心开展的3期试验,我们以2∶1的比例将154例慢性肾脏病患者随机分组,分别以双盲方式接受每周3次、为期8周的罗沙司他或安慰剂治疗。基线时所有患者的血红蛋白水平均为7.0~10.0 g/dL。随机化试验阶段之后是18周的开放标签阶段,所有患者均接受罗沙司他治疗;胃肠外补铁暂停。主要终点是第7~9周的平均血红蛋白水平相对于基线的平均变化。

 

结果

在主要分析期间,罗沙司他组的血红蛋白水平相对于基线的平均(±SD)变化为升高1.9±1.2 g/dL,而安慰剂组为降低0.4±0.8 g/dL(P<0.001)。罗沙司他组的铁调素水平(铁调素水平降低与铁利用率增加相关)相对于基线的平均降幅为56.14±63.40 ng/mL,而安慰剂组为15.10±48.06 ng/mL。罗沙司他组的总胆固醇水平相对于基线的降幅为40.6 mg/dL,而安慰剂组为7.7 mg/dL。罗沙司他组的高钾血症和代谢性酸中毒发生率高于安慰剂组。罗沙司他纠正和维持血红蛋白的疗效在18周开放标签阶段得以维持。

 

结论

在未接受透析的中国慢性肾脏病患者中,8周治疗后罗沙司他组的平均血红蛋白水平高于安慰剂组。在本试验的18周开放标签阶段,罗沙司他持续有效(由珐博进和珐博进[中国]医药技术开发有限公司资助;在ClinicalTrials.gov注册号为NCT02652819)。





作者信息

Nan Chen, M.D., Chuanming Hao, M.D., Ph.D., Xiaomei Peng, B.Sc., Hongli Lin, M.D., Ph.D., Aiping Yin, Ph.D., Li Hao, M.Sc., Ye Tao, M.D., Xinling Liang, M.D., Ph.D., Zhengrong Liu, M.Sc., Changying Xing, M.D., Ph.D., Jianghua Chen, M.Sc., Laimin Luo, M.Sc., Li Zuo, M.D., Ph.D., Yunhua Liao, M.Sc., Bi-Cheng Liu, M.D., Ph.D., Robert Leong, M.D., Chunrong Wang, M.D., Cameron Liu, Ph.D., Thomas Neff, Lynda Szczech, M.D., M.S.C.E., and Kin-Hung P. Yu, M.D.
From the Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (N.C.), and the Division of Nephrology, Huashan Hospital Fudan University (C.H.), Shanghai, the Department of Nephrology, People’s Hospital of Guangxi Zhuang Autonomous Region (X.P.), and the Department of Nephrology, First Affiliated Hospital of Guangxi Medical University (Y.L.), Nanning, the First Affiliated Hospital of Dalian Medical University, Dalian (H.L.), the Department of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an (A.Y.), the Department of Nephrology, Second Hospital of Anhui Medical University, Hefei (L.H.), West China Hospital Sichuan University, Chengdu (Y.T.), the Division of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences (X.L.), and the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research (Z.L.), Guangzhou, the Department of Nephrology, First Affiliated Hospital (Jiangsu Province Hospital), Nanjing Medical University (C.X.), and the Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine (B.-C.L.), Nanjing, First Affiliated Hospital of Zhejiang University, Hangzhou (J.C.), First Affiliated Hospital of Nanchang University, Nanchang (L.L.), and the Department of Nephrology, Peking University People’s Hospital, Beijing (L.Z.) — all in China; and FibroGen, San Francisco (R.L., C.W., C.L., T.N., L.S., K.-H.P.Y.). Address reprint requests to Dr. N. Chen at the Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Rd., Shanghai 200025, China, or at nanchenmd@hotmail.com.

 

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