{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T14:26:36Z","timestamp":1756995996571,"version":"3.40.5"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors, which have recently become clinically available for treating renal anemia, are attracting attention for their novel mechanisms of action.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Relationships of reticulocyte hemoglobin content (CHr), which reflects recent Hb synthesis, with serum ferritin (s-ft) and transferrin saturation (TSAT) were examined in 30 patients on hemodialysis after switching from darbepoetin alfa (DA) to roxadustat (Rox). Iron deficiency was defined as CHr &lt; 32.0 pg. Cutoff values of s-ft and TSAT were determined using receiver operating characteristic curves for the endpoint CHr \u2265 32.0 pg. Logistic analysis was performed with the reference group having s-ft or TSAT below the corresponding cutoff value (low vs high).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>With the endpoint CHr \u2265 32.0 pg on Day 0, cutoff values for s-ft and TSAT were respectively 49.7 ng\/mL and 21.6% on Day 0 and 35.5 ng\/mL and 16.2% on Day 28. With the endpoint CHr \u2265 32.0 pg on Day 28, cutoff values for s-ft and TSAT on Day 0 were 81.6 ng\/mL and 23.9%, respectively. According to multivariable logistic analysis, the odds ratios of CHr \u2265 32.0 pg on Day 0 were significantly higher for high TSAT on Day 0 [34.7 (95% CI 2.42\u2013131.0), p&lt;0.003] and Day 28 [24.8 (95% CI 2.75\u2013224.0), p = 0.004]. There were no significant differences by s-ft. Odd ratios of CHr \u2265 32.0 pg on Day 28 were also significantly higher for high s-ft on Day 0 [16.0 (95% CI 1.57\u2013163.0), p = 0.019] and high TSAT on Day 0 [13.5 (95% CI 1.24\u2013147.0), p&lt;0.033].<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results suggest Hb synthesis was maintained with lower TSAT and s-ft during Rox therapy compared with DA therapy. To avoid iron deficiency during the 4 weeks after switching DA to Rox, ideal s-ft and TSAT levels before the switch are 81.6 ng\/mL and 23.9%, respectively.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0252439","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T17:26:54Z","timestamp":1624037214000},"page":"e0252439","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypoxia-inducible factor prolyl hydroxylase domain inhibitor may maintain hemoglobin synthesis at lower serum ferritin and transferrin saturation levels than darbepoetin alfa"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-9711","authenticated-orcid":true,"given":"Chie","family":"Ogawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohisa","family":"Tomosugi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunimi","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"pone.0252439.ref001","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1093\/ndt\/gfs368","article-title":"Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients","volume":"28","author":"M Rattanasompattikul","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"pone.0252439.ref002","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s11255-018-2062-z","article-title":"Impact of serum hepcidin and inflammatory markers on resistance to erythropoiesis-stimulating therapy in haemodialysis patients","volume":"51","author":"DA El Sewefy","year":"2019","journal-title":"Int Urol Nephrol"},{"key":"pone.0252439.ref003","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":"GL Semenza","year":"1992","journal-title":"Mol Cell Biol"},{"key":"pone.0252439.ref004","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1172\/JCI30117","article-title":"Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo","volume":"117","author":"EB Rankin","year":"2007","journal-title":"J Clin Invest"},{"key":"pone.0252439.ref005","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1182\/blood-2011-01-258467","article-title":"Hepcidin and iron regulation, 10 years later","volume":"117","author":"T. 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