{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T09:43:02Z","timestamp":1774604582474,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020141","name":"Akebia Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hemodialysis International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Erythropoiesis\u2010stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)\u2013related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO\n                      <jats:sub>2<\/jats:sub>\n                      VATE trials in patients with dialysis\u2010dependent CKD (DD\u2010CKD) demonstrated vadadustat's noninferiority compared with darbepoetin alfa. To determine vadadustat's potential to treat anemia, including in patients requiring high ESA doses, its safety and efficacy were compared with those of darbepoetin alfa across prespecified baseline ESA dose subgroups in the prevalent DD\u2010CKD INNO\n                      <jats:sub>2<\/jats:sub>\n                      VATE trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We compared the safety and efficacy of vadadustat versus darbepoetin alfa across prespecified baseline ESA dose subgroups (low [\u2264\u200990\u2009U\/kg\/week], intermediate [&gt;\u200990 and &lt;\u2009300\u2009U\/kg\/week], or high [\u2265\u2009300\u2009U\/kg\/week]) in the INNO\n                      <jats:sub>2<\/jats:sub>\n                      VATE prevalent trial. The primary safety endpoint was time to first adjudicated major adverse cardiovascular event (MACE). Primary and secondary efficacy endpoints were mean hemoglobin level change from baseline at weeks 24\u201336 and weeks 40\u201352, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Compared with darbepoetin alfa, first MACE hazard ratios for vadadustat were 0.99 (95% CI, 0.81\u20131.23), 0.93 (95% CI, 0.74\u20131.18), and 0.62 (95% CI, 0.34\u20131.14) for low, intermediate, and high baseline ESA dose subgroups, respectively (interaction\n                      <jats:italic>p\u2009=<\/jats:italic>\n                      \u20090.92). Vadadustat was noninferior to darbepoetin alfa in hemoglobin change from baseline to primary evaluation period, with mean differences (vadadustat\u2013darbepoetin alfa) of \u22120.10\u2009g\/dL (95% CI, \u22120.19 to \u22120.02), \u22120.20\u2009g\/dL (95% CI, \u22120.30 to \u22120.09), and \u22120.39\u2009g\/dL (95% CI, \u22120.67 to \u22120.11) for low, intermediate, and high ESA dose subgroups, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Comparing safety and efficacy by baseline ESA dose among patients with CKD on maintenance dialysis, vadadustat was noninferior to darbepoetin alfa for all ESA dose subgroups, including patients with high baseline ESA requirements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hdi.70034","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:38:06Z","timestamp":1765442286000},"page":"80-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease\u2013Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis\u2010Stimulating Agent Dose"],"prefix":"10.1111","volume":"30","author":[{"given":"Alan","family":"Jardine","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven K.","family":"Burke","sequence":"additional","affiliation":[{"name":"Akebia Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenli","family":"Luo","sequence":"additional","affiliation":[{"name":"Akebia Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Minga","sequence":"additional","affiliation":[{"name":"Akebia Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Sarnak","sequence":"additional","affiliation":[{"name":"Division of Nephrology Tufts Medical Center  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang C.","family":"Winkelmayer","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Medicine, and Richard L. Roudebush Veterans Administration Medical Center Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn M.","family":"Chertow","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Epidemiology and Population Health, and Health Policy Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai\u2010Uwe","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Koury","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Vanderbilt University Medical Center  Nashville Tennesse USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.03.020"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1987.241"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084943"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011111078"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2020.12.003"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013010030"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.82"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2016.02.001"},{"issue":"4","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes CKDWG","year":"2024","journal-title":"Kidney International"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad250"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000516901"},{"key":"e_1_2_12_13_1","volume-title":"Mircera (Methoxy Polyethylene Glycol\u2010Epoetin Beta). Package Insert","author":"Vifor (International) Inc","year":"2019"},{"key":"e_1_2_12_14_1","volume-title":"Aranesp (Darbepoetin Alfa). Prescribing Information","author":"Amgen, Inc","year":"2019"},{"key":"e_1_2_12_15_1","volume-title":"Epogen (Epoetin Alfa). Prescribing Information","author":"Amgen, Inc","year":"2018"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03970318"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e02045"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2020.01.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaa212"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025956"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035938"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020091311"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab055"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3342"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15310"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa204"},{"issue":"2","key":"e_1_2_12_27_1","first-page":"1","article-title":"Revised European Best Practice Guidelines for the Management of Anaemia in Patients With Chronic Renal Failure","volume":"19","author":"Locatelli F.","year":"2004","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X154024"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.4212\/cjhp.v65i6.1192"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61599-2"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90654-1"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01590215"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfaa038"},{"key":"e_1_2_12_34_1","volume-title":"ABIM Laboratory Test Reference Ranges \u2013 January 2024","author":"American Board of Internal Medicine","year":"2024"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.07.026"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.05.031"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xkme.2020.06.008"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000528696"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.32.20055"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2326648"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.8.2340.2340"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1744-9987.2012.01089.x"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.598148"}],"container-title":["Hemodialysis International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hdi.70034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hdi.70034","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hdi.70034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:38:42Z","timestamp":1768901922000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hdi.70034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/hdi.70034"],"URL":"https:\/\/doi.org\/10.1111\/hdi.70034","archive":["Portico"],"relation":{},"ISSN":["1492-7535","1542-4758"],"issn-type":[{"value":"1492-7535","type":"print"},{"value":"1542-4758","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"assertion":[{"value":"2025-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}