Literature DB >> 33567688

Whether Prolyl Hydroxylase Blocker-Roxadustat-In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future?

Władysław Grzeszczak1, Dariusz Szczyra1, Mirosław Śnit1.   

Abstract

In patients with chronic kidney disease (CKD), anemia develops gradually, which is primarily due to an inadequate synthesis of erythropoietin by the kidneys, as well as to iron disorders in the body, blood loss, shortened erythrocyte survival and inflammation. The currently accepted treatment employs iron, vitamin B12, folic acid supplementation and the use of erythropoiesis stimulants, which are administered only parenterally. Research is currently underway on the new erythropoiesis drugs that can be orally administered, i.e., hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI) inhibitors which temporarily block propyl hydroxylase [PHD] catalysis and promote a transient increase in the expression of genes regulated by HIF, including kidney and liver erythropoietin [EPO]. Roxadustat is the first oral drug in this class and a potent HIF-PHD inhibitor, exerted to treat anemia in patients with CKD. In phase 1, 2 and 3 studies with CKD-affected patients, roxadustat was more effective to stimulate erythropoiesis for anemia correction than previously used drugs. Roxadustat can be orally given, unlike other erythropoiesis drugs with parenteral administration only, which grants roxadustat a considerable advantage. Our paper presents the results of studies with roxadustat applied for the treatment of anemia in CKD patients with or without dialysis. We are currently not yet able to know the exact role of roxadustat in the treatment of anemia in patients with CKD, but time will tell. It is possible that roxadustat has benefits an iron metabolism and cardiovascular risk.

Entities:  

Keywords:  anemia; chronic kidney disease; roxadustat

Mesh:

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Year:  2021        PMID: 33567688      PMCID: PMC7914880          DOI: 10.3390/ijerph18041612

Source DB:  PubMed          Journal:  Int J Environ Res Public Health        ISSN: 1660-4601            Impact factor:   3.390


  34 in total

1.  Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD.

Authors:  Wanja M Bernhardt; Michael S Wiesener; Paul Scigalla; James Chou; Roland E Schmieder; Volkmar Günzler; Kai-Uwe Eckardt
Journal:  J Am Soc Nephrol       Date:  2010-11-29       Impact factor: 10.121

2.  Acceleration of Diabetic Wound Healing with PHD2- and miR-210-Targeting Oligonucleotides.

Authors:  Anne Dallas; Artem Trotsyuk; Heini Ilves; Clark A Bonham; Melanie Rodrigues; Karl Engel; Janos A Barrera; Nina Kosaric; Zachary A Stern-Buchbinder; Aleksandr White; Kenneth J Mandell; Paula T Hammond; Jonathan Mansbridge; Sumedha Jayasena; Geoffrey C Gurtner; Brian H Johnston
Journal:  Tissue Eng Part A       Date:  2018-06-29       Impact factor: 3.845

Review 3.  Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients.

Authors:  Francesco Locatelli; Steven Fishbane; Geoffrey A Block; Iain C Macdougall
Journal:  Am J Nephrol       Date:  2017-01-25       Impact factor: 3.754

4.  A Phase 3, Multicenter, Randomized, Two-Arm, Open-Label Study of Intermittent Oral Dosing of Roxadustat for the Treatment of Anemia in Japanese Erythropoiesis-Stimulating Agent-Naïve Chronic Kidney Disease Patients Not on Dialysis.

Authors:  Tadao Akizawa; Yusuke Yamaguchi; Tetsuro Otsuka; Michael Reusch
Journal:  Nephron       Date:  2020-06-24       Impact factor: 2.847

5.  Erythropoietin and a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) lowers FGF23 in a model of chronic kidney disease (CKD).

Authors:  Megan L Noonan; Erica L Clinkenbeard; Pu Ni; Elizabeth A Swallow; Samantha P Tippen; Rafiou Agoro; Matthew R Allen; Kenneth E White
Journal:  Physiol Rep       Date:  2020-06

Review 6.  Roxadustat: First Global Approval.

Authors:  Sohita Dhillon
Journal:  Drugs       Date:  2019-04       Impact factor: 9.546

7.  Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.

Authors:  Anatole Besarab; Elena Chernyavskaya; Igor Motylev; Evgeny Shutov; Lalathaksha M Kumbar; Konstantin Gurevich; Daniel Tak Mao Chan; Robert Leong; Lona Poole; Ming Zhong; Khalil G Saikali; Marietta Franco; Stefan Hemmerich; Kin-Hung Peony Yu; Thomas B Neff
Journal:  J Am Soc Nephrol       Date:  2015-10-22       Impact factor: 10.121

8.  Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.

Authors:  Robert Provenzano; Anatole Besarab; Chao H Sun; Susan A Diamond; John H Durham; Jose L Cangiano; Joseph R Aiello; James E Novak; Tyson Lee; Robert Leong; Brian K Roberts; Khalil G Saikali; Stefan Hemmerich; Lynda A Szczech; Kin-Hung Peony Yu; Thomas B Neff
Journal:  Clin J Am Soc Nephrol       Date:  2016-04-19       Impact factor: 8.237

9.  Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.

Authors:  Anatole Besarab; Robert Provenzano; Joachim Hertel; Raja Zabaneh; Stephen J Klaus; Tyson Lee; Robert Leong; Stefan Hemmerich; Kin-Hung Peony Yu; Thomas B Neff
Journal:  Nephrol Dial Transplant       Date:  2015-08-03       Impact factor: 5.992

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  2 in total

Review 1.  Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment.

Authors:  Lukas Lanser; Dietmar Fuchs; Katharina Kurz; Günter Weiss
Journal:  Nutrients       Date:  2021-10-22       Impact factor: 5.717

Review 2.  Roxadustat: Not just for anemia.

Authors:  Xiaoyu Zhu; Lili Jiang; Xuejiao Wei; Mengtuan Long; Yujun Du
Journal:  Front Pharmacol       Date:  2022-08-29       Impact factor: 5.988

  2 in total

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