{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:16:31Z","timestamp":1790662591729,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T00:00:00Z","timestamp":1424131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Hyporesponsiveness to erythropoiesis\u2010stimulating agents (ESAs) is clinically and economically important in the treatment of anaemia in chronic kidney disease (CKD) patients. Previous studies focused on baseline predictors of ESA hyporesponsiveness, rather than factors associated with the transition to this state. Reversibility of ESA hyporesponsiveness has also not been studied previously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Case\u2010crossover methodology was applied to a cohort of 6645 European CKD patients undergoing haemodialysis and prescribed ESAs. Ninety\u2010day ESA exposure periods were defined, haemoglobin (Hb) response was calculated using the last 30\u2009days of one period and the first 30\u2009days of the next, and periods were classified based on a median ESA dose (80.8\u2009IU\/kg\/week) and a 10\u2009g\/dL Hb threshold. Clinical, dialysis and laboratory data from patients' first hyporesponsive \u2018case\u2019 period was compared with the preceding responsive \u2018control\u2019 period using conditional logistic regression. A similar approach was applied to hyporesponsiveness reversal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the patients, 672 experienced hyporesponsiveness periods with preceding responsive periods; 711 reversed to normality from hyporesponsiveness periods. Transition to hyporesponsiveness was associated with hospitalization, vascular access changes or worsening inflammation, with these factors accounting for over two\u2010thirds of transitions. Findings were largely insensitive to alternative ESA doses and Hb thresholds. Continued hospitalization, catheter insertion and uncontrolled secondary hyperparathyroidism were associated with a lack of regain of responsiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Transition to hyporesponsiveness is linked to the development of conditions such as hospitalization events, vascular access issues or episodes of systemic inflammation. However, a third of hyporesponsive episodes remain unexplained. \u00a9 2015 The Authors. <jats:italic>Pharmacoepidemiology and Drug Safety<\/jats:italic> published by John Wiley &amp; Sons Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.3755","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T15:52:54Z","timestamp":1424188374000},"page":"414-426","source":"Crossref","is-referenced-by-count":25,"title":["Factors precipitating erythropoiesis\u2010stimulating agent responsiveness in a European haemodialysis cohort: case\u2010crossover study"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-9506","authenticated-orcid":false,"given":"Iain A.","family":"Gillespie","sequence":"first","affiliation":[{"name":"Center for Observational Research (CfOR) Amgen Ltd  Uxbridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain 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