{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:32:36Z","timestamp":1792297956626,"version":"4.4.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Roxadustat (FG-4592), an oral hypoxia\u2013inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>The 145 patients with nondialysis CKD and hemoglobin \u226410.5 g\/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of \u22651.0 g\/dl from baseline and hemoglobin of \u226511.0 g\/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency\/severity of adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat\u2013induced hemoglobin increases were independent of baseline C\u2013reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (\u00b1SD) of 1.83 (\u00b10.09) g\/dl (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Overall mean total cholesterol level was reduced by a mean (\u00b1SD) of 26 (\u00b130) mg\/dl (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) after 8 weeks of therapy, independent of the use of statins or other lipid\u2013lowering agents. No drug\u2013related serious adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.06890615","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T22:58:45Z","timestamp":1461106725000},"page":"982-991","source":"Crossref","is-referenced-by-count":260,"title":["Oral Hypoxia\u2013Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD"],"prefix":"10.2215","volume":"11","author":[{"given":"Robert","family":"Provenzano","sequence":"first","affiliation":[{"name":"St. John Hospital and Medical Center, Detroit, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatole","family":"Besarab","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao H.","family":"Sun","sequence":"additional","affiliation":[{"name":"Apex Research of Riverside, Riverside, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Diamond","sequence":"additional","affiliation":[{"name":"San Antonio Kidney Disease Center, San Antonio, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Durham","sequence":"additional","affiliation":[{"name":"Palmetto Nephrology, Professional Association, Orangeburg, South Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Cangiano","sequence":"additional","affiliation":[{"name":"Nephrology Private Practice, San Juan, Puerto Rico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Aiello","sequence":"additional","affiliation":[{"name":"Mountain Kidney and Hypertension Associates, Professional Association, Asheville, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Novak","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Henry Ford Hospital, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyson","family":"Lee","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Leong","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Roberts","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil G.","family":"Saikali","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hemmerich","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda A.","family":"Szczech","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin-Hung Peony","family":"Yu","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Neff","sequence":"additional","affiliation":[{"name":"FibroGen, Inc., San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,4,19]]},"reference":[{"issue":"Suppl 4","key":"B1-20230813","doi-asserted-by":"crossref","first-page":"S133","DOI":"10.1016\/S0272-6386(98)70176-3","article-title":"Trends in anemia treatment with erythropoietin usage and patient outcomes.","volume":"32","author":"Collins","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1001\/jama.298.17.2038","article-title":"Prevalence of chronic kidney disease in the United States.","volume":"298","author":"Coresh","year":"2007","journal-title":"JAMA"},{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1056\/NEJM198701083160203","article-title":"Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. 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