Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience

被引：142

作者：

Sanghani, Neil S.

Haase, Volker H.

机构：

[1] Vanderbilt Univ, Dept Med, Med Ctr, Nashville, TN 37232 USA

[2] Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden

[3] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Sch Med, Program Canc Biol, Nashville, TN 37232 USA

来源：

ADVANCES IN CHRONIC KIDNEY DISEASE | 2019年 / 26卷 / 04期

关键词：

Anemia; Chronic kidney disease; Prolyl hydroxylase domain; Hypoxia-inducible factor; Erythropoietin; PROLYL HYDROXYLASE INHIBITOR; CHRONIC KIDNEY-DISEASE; ROXADUSTAT FG-4592; EPOETIN-ALPHA; MAINTENANCE-HEMODIALYSIS; ERYTHROPOIETIC RESPONSE; HEPCIDIN EXPRESSION; REGULATES HEPCIDIN; DARBEPOETIN-ALPHA; TARGETING HYPOXIA;

D O I：

10.1053/j.ackd.2019.04.004

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Prolyl hydroxylase domain oxygen sensors are dioxygenases that regulate the activity of hypoxia-inducible factor (HIF), which controls renal and hepatic erythropoietin production and coordinates erythropoiesis with iron metabolism. Small molecule inhibitors of prolyl hydroxylase domain dioxygenases (HIF-PHI [prolyl hydroxylase inhibitor]) stimulate the production of endogenous erythropoietin and improve iron metabolism resulting in efficacious anemia management in patients with CKD. Three oral HIF-PHIS-daprodustat, roxadustat, and vadadustat-have now advanced to global phase III clinical development culminating in the recent licensing of roxadustat for oral anemia therapy in China. Here, we survey current clinical experience with HIF-PHIs, discuss potential therapeutic advantages, and deliberate over safety concerns regarding long-term administration in patients with renal anemia. (C) 2019 by the National Kidney Foundation, Inc. All rights reserved.

引用

收藏

页码：253 / 266

页数：14

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