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缺氧诱导因子稳定剂作为一种新兴的治疗慢性肾脏病相关贫血的方法:美国国家肾脏基金会科学研讨会报告。

Hypoxia-Inducible Factor Stabilization as an Emerging Therapy for CKD-Related Anemia: Report From a Scientific Workshop Sponsored by the National Kidney Foundation.

机构信息

Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana.

Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Am J Kidney Dis. 2021 Nov;78(5):709-718. doi: 10.1053/j.ajkd.2021.06.019. Epub 2021 Jul 28.

Abstract

The National Kidney Foundation convened an interdisciplinary international workshop in March 2019 to discuss the potential role of a new class of agents for the treatment of anemia in patients with chronic kidney disease (CKD): the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). International experts with expertise in physiology, biochemistry, structural chemistry, translational medicine, and clinical management of anemia participated. Participants reviewed the unmet needs of current anemia treatment, the biology of hypoxia-inducible factor, the pharmacology of prolyl hydroxylase inhibitors, and the results of phase 2 clinical trials of HIF-PHIs among patients with CKD, both those treated by dialysis and those not receiving kidney replacement therapy. The results of key phase 3 clinical trials of HIF-PHIs available as of the time of writing are also included in this report, although they appeared after the workshop was completed. Participants in the workshop developed a number of recommendations for further examination of HIF-PHIs, which are summarized in this report and include long-term safety issues, potential benefits, and practical considerations for implementation including patient and provider education.

摘要

美国国家肾脏基金会于 2019 年 3 月召集了一次跨学科国际研讨会,讨论了一类新的药物在治疗慢性肾脏病(CKD)患者贫血中的潜在作用:缺氧诱导因子脯氨酰羟化酶抑制剂(HIF-PHIs)。参与会议的专家具有生理学、生物化学、结构化学、转化医学和贫血临床管理方面的专业知识。与会者回顾了当前贫血治疗的未满足需求、缺氧诱导因子的生物学、脯氨酰羟化酶抑制剂的药理学以及接受透析和未接受肾脏替代治疗的 CKD 患者中 HIF-PHIs 的 2 期临床试验结果。本报告还纳入了截至撰写时可获得的 HIF-PHIs 的关键 3 期临床试验结果,尽管这些结果是在研讨会结束后出现的。研讨会的参与者为进一步研究 HIF-PHIs 提出了一些建议,这些建议在本报告中进行了总结,包括长期安全性问题、潜在获益以及包括患者和提供者教育在内的实施的实际考虑因素。

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