{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:04:20Z","timestamp":1791475460074,"version":"4.3.4"},"reference-count":96,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"am","delay-in-days":311,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology &amp; Therapeutics"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.pharmthera.2022.108272","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T19:13:15Z","timestamp":1661627595000},"page":"108272","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"special_numbering":"C","title":["Future perspectives of anemia management in chronic kidney disease using hypoxia-inducible factor-prolyl hydroxylase inhibitors"],"prefix":"10.1016","volume":"239","author":[{"given":"Mai","family":"Sugahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmthera.2022.108272_bb0005","doi-asserted-by":"crossref","DOI":"10.1159\/000523961","article-title":"Desidustat in anemia due to non-dialysis-dependent chronic kidney disease: A phase 3 study (DREAM-ND)","author":"Agrawal","year":"2022","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0010","first-page":"1810","article-title":"Phase 3 study of roxadustat to treat anemia in non-dialysis-dependent CKD","volume":"6","author":"Akizawa","year":"2021","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0015","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000496929","article-title":"A placebo-controlled, randomized trial of enarodustat in patients with chronic kidney disease followed by long-term trial","volume":"49","author":"Akizawa","year":"2019","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0020","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.ekir.2021.04.037","article-title":"A phase 3 study of enarodustat in anemic patients with CKD not requiring dialysis: The SYMPHONY ND study","volume":"6","author":"Akizawa","year":"2021","journal-title":"Kidney International Reports"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0025","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1159\/000517053","article-title":"A phase 3 study of enarodustat (JTZ-951) in Japanese hemodialysis patients for treatment of anemia in chronic kidney disease: SYMPHONY HD study","volume":"7","author":"Akizawa","year":"2021","journal-title":"Kidney Diseases"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0030","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2215\/CJN.16011219","article-title":"Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia: A randomized, double-blind, phase 3 trial","volume":"15","author":"Akizawa","year":"2020","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0035","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2215\/CJN.16011219","article-title":"Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia. A randomized, double-blind, phase 3 trial","volume":"15","author":"Akizawa","year":"2020","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0040","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1016\/j.ekir.2021.07.015","article-title":"Molidustat for Japanese patients with renal anemia receiving dialysis","volume":"6","author":"Akizawa","year":"2021","journal-title":"Kidney International Reports"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0045","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/ndt\/gfab191","article-title":"Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: A phase 3, randomized, open-label, active-controlled study (DOLOMITES)","volume":"36","author":"Barratt","year":"2021","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0050","doi-asserted-by":"crossref","first-page":"5345","DOI":"10.1007\/s12325-021-01903-7","article-title":"Efficacy and cardiovascular safety of Roxadustat in dialysis-dependent chronic kidney disease: Pooled analysis of four phase 3 studies","volume":"38","author":"Barratt","year":"2021","journal-title":"Advances in Therapy"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0055","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1681\/ASN.2005121302","article-title":"Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure","volume":"17","author":"Bernhardt","year":"2006","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0060","doi-asserted-by":"crossref","first-page":"21276","DOI":"10.1073\/pnas.0903978106","article-title":"Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model","volume":"106","author":"Bernhardt","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0065","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1093\/emboj\/cdg392","article-title":"HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1\u03b1 in normoxia","volume":"22","author":"Berra","year":"2003","journal-title":"The EMBO Journal"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0070","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJM199808273390903","article-title":"The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin","volume":"339","author":"Besarab","year":"1998","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0075","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1681\/ASN.2015030241","article-title":"Roxadustat (FG-4592): Correction of anemia in incident dialysis patients","volume":"27","author":"Besarab","year":"2016","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0080","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/ndt\/gfv302","article-title":"Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients","volume":"30","author":"Besarab","year":"2015","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0085","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1093\/nar\/27.21.4223","article-title":"HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation","volume":"27","author":"Bianchi","year":"1999","journal-title":"Nucleic Acids Research"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0090","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.ekir.2021.04.007","article-title":"A randomized trial of Roxadustat in anemia of kidney failure: SIERRAS study","volume":"6","author":"Charytan","year":"2021","journal-title":"Kidney International Reports"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0095","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJMoa1901713","article-title":"Roxadustat treatment for anemia in patients undergoing long-term dialysis","volume":"381","author":"Chen","year":"2019","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0100","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMoa1813599","article-title":"Roxadustat for anemia in patients with kidney disease not receiving dialysis","volume":"381","author":"Chen","year":"2019","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0105","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1056\/NEJMoa2035938","article-title":"Vadadustat in patients with anemia and non-dialysis-dependent CKD","volume":"384","author":"Chertow","year":"2021","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0110","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ekir.2020.11.034","article-title":"Roxadustat for CKD-related anemia in non-dialysis patients","volume":"6","author":"Coyne","year":"2020","journal-title":"Kidney International Reports"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0115","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1007\/s12325-021-01904-6","article-title":"Roxadustat for the maintenance treatment of anemia in patients with end-stage kidney disease on stable dialysis: A European phase 3, randomized, open-label, active controlled study (PYRENEES)","volume":"38","author":"Csiky","year":"2021","journal-title":"Advances in Therapy"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0120","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa062276","article-title":"Normalization of hemoglobin level in patients with chronic kidney disease and anemia","volume":"355","author":"Dr\u00fceke","year":"2006","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0125","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.kint.2019.10.007","article-title":"The noblesse of kidney physiology","volume":"96","author":"Eckardt","year":"2019","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0130","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1056\/NEJMoa2025956","article-title":"Safety and efficacy of vadadustat for anemia in patients undergoing dialysis","volume":"384","author":"Eckardt","year":"2021","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0135","author":"EMA"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0140","author":"FDA"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0145","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1681\/ASN.2020081150","article-title":"Roxadustat for treating anemia in patients with CKD not on dialysis: Results from a randomized phase 3 study","volume":"32","author":"Fishbane","year":"2021","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0150","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1681\/ASN.2020111638","article-title":"Roxadustat versus epoetin alfa for treating anemia in patients with chronic kidney disease on dialysis: Results from the randomized phase 3 ROCKIES study","volume":"33","author":"Fishbane","year":"2022","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0155","doi-asserted-by":"crossref","DOI":"10.1159\/000523949","article-title":"Desidustat in anemia due to dialysis-dependent chronic kidney disease: A phase 3 study (DREAM-D)","author":"Gang","year":"2022","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0160","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1073\/pnas.0608382104","article-title":"Acute postnatal ablation of Hif-2\u03b1 results in anemia","volume":"104","author":"Gruber","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of the USA"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0165","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.kint.2021.03.019","article-title":"Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone","volume":"100","author":"Hanudel","year":"2021","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0170","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1681\/ASN.2006090998","article-title":"Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury","volume":"19","author":"Hill","year":"2008","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0175","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1681\/ASN.2014111139","article-title":"Four-week studies of oral hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 for treatment of anemia","volume":"27","author":"Holdstock","year":"2016","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0180","doi-asserted-by":"crossref","first-page":"9361","DOI":"10.1128\/MCB.23.24.9361-9374.2003","article-title":"Differential roles of hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) and HIF-2\u03b1 in hypoxic gene regulation","volume":"23","author":"Hu","year":"2003","journal-title":"Molecular and Cellular Biology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0185","doi-asserted-by":"crossref","first-page":"9382","DOI":"10.1074\/jbc.M117.788562","article-title":"Hypoxia-inducible factor 1\u03b1 activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver","volume":"292","author":"Hwang","year":"2017","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0190","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.kint.2019.10.020","article-title":"Prolyl hydroxylase inhibition protects the kidneys from ischemia via upregulation of glycogen storage","volume":"97","author":"Ito","year":"2020","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0195","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIF\u03b1 targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0200","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-\u03b1 to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","author":"Jaakkola","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0205","doi-asserted-by":"crossref","first-page":"782","DOI":"10.3324\/haematol.2019.245092","article-title":"Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats","volume":"106","author":"Jimenez","year":"2021","journal-title":"Hematologica"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0210","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.1021\/acs.jmedchem.7b01686","article-title":"Prolyl hydroxylase inhibitors: A breakthrough in the therapy of anemia associated with chronic diseases","volume":"61","author":"Joharapurkar","year":"2018","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0215","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0272-6386(03)00915-6","article-title":"Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients","volume":"42","author":"Kalantar-Zadeh","year":"2003","journal-title":"American Journal of Kidney Diseases"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0220","doi-asserted-by":"crossref","first-page":"F1023","DOI":"10.1152\/ajprenal.90209.2008","article-title":"Stable expression of HIF-1\u03b1 in tubular epithelial cells promotes interstitial fibrosis","volume":"295","author":"Kimura","year":"2008","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0225","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.kint.2018.06.008","article-title":"HIF-1\u03b1 promotes cyst progression in a mouse model of autosomal dominant polycystic kidney disease","volume":"94","author":"Kraus","year":"2018","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0230","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/14656566.2021.1993821","article-title":"An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease","volume":"23","author":"Kurata","year":"2022","journal-title":"Expert Opinion on Pharmacotherapy"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0235","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104747","article-title":"Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis","volume":"155","author":"Liu","year":"2020","journal-title":"Pharmacological Research"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0240","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1172\/JCI63924","article-title":"Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis","volume":"122","author":"Liu","year":"2012","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0245","first-page":"991","article-title":"Nephrol Dial Transplant","volume":"21","author":"Locatelli","year":"2006"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0250","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2215\/CJN.02510218","article-title":"Effects of molidustat in the treatment of anemia in CKD","volume":"14","author":"Macdougall","year":"2019","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0255","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1159\/000464476","article-title":"Clinical trial of vadadustat in patients with anemia secondary to stage 3 or 4 chronic kidney disease","volume":"45","author":"Martin","year":"2017","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0260","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3324\/haematol.2011.056119","article-title":"Hepatic hypoxia-inducible factor-2 down-regulates hepcidin expression in mice through an erythropoietin-mediated increase in erythropoiesis","volume":"97","author":"Mastrogiannaki","year":"2012","journal-title":"Haematologica"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0265","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1097\/01.ASN.0000074239.22357.06","article-title":"Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats","volume":"14","author":"Matsumoto","year":"2003","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0270","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1182\/blood-2007-10-117812","article-title":"Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure","volume":"111","author":"Minamishima","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0275","doi-asserted-by":"crossref","first-page":"21048","DOI":"10.1074\/jbc.M000636200","article-title":"Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency","volume":"275","author":"Mukhopadhyay","year":"2000","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0280","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000513103","article-title":"Daprodustat compared with epoetin beta pegol for anemia in Japanese patients not on dialysis: A 52-week randomized open-label phase 3 trial","volume":"62","author":"Nangaku","year":"2021","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0285","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1681\/ASN.2020091311","article-title":"Phase 3 randomized study comparing vadadustat with darbepoetin alfa for anemia in Japanese patients with nondialysis-dependent CKD","volume":"32","author":"Nangaku","year":"2021","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0290","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/ndt\/gfab055","article-title":"Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: A phase 3, multicenter, randomized, double-blind study","volume":"36","author":"Nangaku","year":"2021","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0295","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1681\/ASN.2013090990","article-title":"Activation of hypoxia-inducible factors prevents diabetic nephropathy","volume":"26","author":"Nordquist","year":"2015","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0300","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1159\/000500232","article-title":"Outcomes of desidustat treatment in people with anemia and chronic kidney disease: A phase 2 study","volume":"49","author":"Parmar","year":"2019","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0305","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1056\/NEJMoa0907845","article-title":"A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease","volume":"361","author":"Pfeffer","year":"2009","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0310","author":"PMDA"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0315","doi-asserted-by":"crossref","first-page":"982","DOI":"10.2215\/CJN.06890615","article-title":"Oral hypoxia-inducible factor prolyl hydroxylase inhibitor Roxadustat (FG-4592) for the treatment of anemia in patients with CKD","volume":"11","author":"Provenzano","year":"2016","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0320","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/ndt\/gfab051","article-title":"Roxadustat for anemia in patients with end-stage renal disease incident to dialysis","volume":"36","author":"Provenzano","year":"2021","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0325","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.2215\/CJN.16191020","article-title":"Efficacy and cardiovascular safety of roxadustat for treatment of anemia in patients with non-dialysis-dependent CKD","volume":"16","author":"Provenzano","year":"2021","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0330","doi-asserted-by":"crossref","first-page":"9369","DOI":"10.1021\/jm400386j","article-title":"Inhibition of hypoxia-inducible factor prolyl hydroxylase domain oxygen sensors: Tricking the body into mounting orchestrated survival and repair responses","volume":"56","author":"Rabinowitz","year":"2013","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0335","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.2337\/db14-0472","article-title":"HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction","volume":"63","author":"Rahtu-Korpela","year":"2014","journal-title":"Diabetes"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0340","doi-asserted-by":"crossref","first-page":"20055","DOI":"10.1074\/jbc.272.32.20055","article-title":"Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1","volume":"272","author":"Rolfs","year":"1997","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0345","first-page":"1217","article-title":"Inhibition of prolyl hydroxylase domain (PHD) by JTZ-951 reduces obesity-related diseases in the liver, white adipose tissue, and kidney in mice with a high-fat diet","volume":"99","author":"Saito","year":"2019","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0350","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.kint.2019.02.016","article-title":"Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis","volume":"96","author":"Schley","year":"2019","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0355","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1182\/blood-2004-05-1695","article-title":"HIF-2\u03b1 regulates murine hematopoietic development in an erythropoietin-dependent manner","volume":"105","author":"Scortegagna","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0360","doi-asserted-by":"crossref","first-page":"5680","DOI":"10.1073\/pnas.88.13.5680","article-title":"Hypoxia-inducible nuclear factors bind to an enhancer element located 3\u2032 to the human erythropoietin gene","volume":"88","author":"Semenza","year":"1991","journal-title":"Proceedings of the National Academy of Sciences of the USA"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0365","first-page":"5447","article-title":"A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation","volume":"12","author":"Semenza","year":"1992","journal-title":"Molecular and Cellular Biology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0370","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cmet.2008.12.012","article-title":"Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency","volume":"9","author":"Shah","year":"2009","journal-title":"Cell Metabolism"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0375","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1042\/BJ20111377","article-title":"Hypoxia-inducible factor-1 (HIF-1) promotes LDL and VLDL uptake through inducing VLDLR under hypoxia","volume":"441","author":"Shen","year":"2012","journal-title":"The Biochemical Journal"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0380","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1093\/ndt\/gfab057","article-title":"Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: A phase 3, randomized, double-blind, placebo-controlled study (ALPS)","volume":"36","author":"Shutov","year":"2021","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0385","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa2113380","article-title":"Daprodustat for the treatment of anemia in patients not undergoing dialysis","volume":"385","author":"Singh","year":"2021","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0390","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1056\/NEJMoa2113379","article-title":"Daprodustat for the treatment of anemia in patients undergoing dialysis","volume":"385","author":"Singh","year":"2021","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0395","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1056\/NEJMoa065485","article-title":"Correction of anemia with epoetin alfa in chronic kidney disease","volume":"355","author":"Singh","year":"2006","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0400","article-title":"Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan chronic kidney disease database (J-CKD-DB)","volume":"15","author":"Sofue","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0405","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0084943","article-title":"Prevalence of anemia in chronic kidney disease in the United States","volume":"9","author":"Stauffer","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0410","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1681\/ASN.2019060582","article-title":"Prolyl hydroxylase domain inhibitor protects against metabolic disorders and associated kidney disease in obese type 2 diabetic mice","volume":"31","author":"Sugahara","year":"2020","journal-title":"The Journal of the American Society of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0415","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.kint.2017.02.035","article-title":"Prolyl hydroxylase domain inhibitors as a novel therapeutic approach against anemia in chronic kidney disease","volume":"92","author":"Sugahara","year":"2017","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0420","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41581-019-0197-5","article-title":"The multifaceted role of iron in renal health and disease","volume":"16","author":"van Swelm","year":"2020","journal-title":"Nature Reviews. Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0425","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/ki.2008.295","article-title":"Secondary analysis of the CHOIR trial epoetin-\u03b1 dose and achieved hemoglobin outcomes","volume":"74","author":"Szczech","year":"2008","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0430","doi-asserted-by":"crossref","first-page":"F1123","DOI":"10.1152\/ajprenal.00081.2005","article-title":"Hypoxia-inducible factor modulates tubular cell survival in cisplatin nephrotoxicity","volume":"289","author":"Tanaka","year":"2005","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0435","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1111\/j.1523-1755.2005.00742.x","article-title":"Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis","volume":"68","author":"Tanaka","year":"2005","journal-title":"Kidney International"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0440","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1161\/CIRCRESAHA.119.316453","article-title":"Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability","volume":"127","author":"Tang","year":"2020","journal-title":"Circulation Research"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0445","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/1744-9987.12962","article-title":"A 24-week anemia correction study of daprodstat in Japanese dialysis patients","volume":"24","author":"Tsubakihara","year":"2020","journal-title":"Therapeutic Apheresis and Dialysis"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0450","doi-asserted-by":"crossref","first-page":"F388","DOI":"10.1152\/ajprenal.00419.2019","article-title":"Effects of a prolyl hydroxylase inhibitor on kidney and cardiovascular complications in a rat model of chronic kidney disease","volume":"318","author":"Uchida","year":"2020","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0455","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0007875","article-title":"Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors","volume":"4","author":"Volke","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0460","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1159\/000518071","article-title":"Efficacy and safety of molidustat for anemia in ESA-na\u00efve nondialysis patients: A randomized, phase 3 trial","volume":"52","author":"Yamamoto","year":"2021","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0465","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1159\/000518072","article-title":"Molidustat for renal anemia in nondialysis patients previously treated with erythropoiesis-stimulating agents: A randomized, open-label, phase 3 study","volume":"52","author":"Yamamoto","year":"2021","journal-title":"American Journal of Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0470","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/nep.13835","article-title":"Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors","volume":"26","author":"Yap","year":"2021","journal-title":"Nephrology"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0475","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.cmet.2019.09.016","article-title":"Adipocyte hypoxia-inducible factor 2\u03b1 suppresses atherosclerosis by promoting adipose ceramide catabolism","volume":"30","author":"Zhang","year":"2019","journal-title":"Cell Metabolism"},{"key":"10.1016\/j.pharmthera.2022.108272_bb0480","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1007\/s11739-021-02738-4","article-title":"Roxadustat for dialysis patients with erythropoietin hypo-responsiveness: A single-center, prospective investigation. (2021)","volume":"16","author":"Zhou","year":"2021","journal-title":"Internal and Emergency Medicine"}],"container-title":["Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725822001668?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725822001668?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T22:29:10Z","timestamp":1759012150000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725822001668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":96,"alternative-id":["S0163725822001668"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmthera.2022.108272","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Future perspectives of anemia management in chronic kidney disease using hypoxia-inducible factor-prolyl hydroxylase inhibitors","name":"articletitle","label":"Article Title"},{"value":"Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmthera.2022.108272","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108272"}}