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In four phase 3, randomized, open\u2010label, clinical trials in dialysis\u2010dependent and non\u2013dialysis\u2010dependent patients with CKD and anemia, the hypoxia\u2010inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis\u2010stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron\u2010binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.<\/jats:p>","DOI":"10.1002\/ajh.26644","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T15:55:25Z","timestamp":1656172525000},"page":"1178-1188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-7694","authenticated-orcid":false,"given":"Mark J.","family":"Koury","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn M.","family":"Chertow","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Uwe","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Fishbane","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Hofstra Northwell School of Medicine  Great Neck New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2830-5469","authenticated-orcid":false,"given":"Tomas","family":"Ganz","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pathology, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker H.","family":"Haase","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Medical Cell Biology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Hanudel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Parfrey","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial University  St John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo E.","family":"Pergola","sequence":"additional","affiliation":[{"name":"Renal Associates PA  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabir","family":"Roy\u2010Chaudhury","sequence":"additional","affiliation":[{"name":"W.G. 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