{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:23:05Z","timestamp":1770693785431,"version":"3.49.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004095","name":"Kyowa Hakko Kirin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erythropoiesis-stimulating agents (ESA) hyporesponsiveness may be linked to malignancy, but studies examining this association are limited. We investigated whether initial ESA hyporesponsiveness and changes in responsiveness may serve as clinical markers reflecting undiagnosed malignancy in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from the BRIGHTEN, a prospective study of NDD-CKD patients with anemia. Initial ESA responsiveness was assessed using the erythropoietin resistance index (ERI-1B), calculated as the ratio of darbepoetin-alfa dose (\u03bcg) to hemoglobin concentration (g\/dL) at 12\u00a0weeks after darbepoetin-alfa initiation. ESA responsiveness trends after 12\u00a0weeks were analyzed using a joint latent class model (JLCM). The associations of both initial ESA responsiveness and ESA responsiveness trends after 12\u00a0weeks with malignancy development were analyzed using a Cox proportional hazards model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 1641 patients analyzed, 44 developed new malignancies. Patients with poor ESA response at 12\u00a0weeks (ERI-1B\u2009&gt;\u20093.8\u00a0\u03bcg\/g\/dL) had a higher incidence of malignancy compared to those with better ESA response (adjusted hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.07\u20134.00). Furthermore, based on the JLCM, patients in the poor response group, characterized by a faster decline in ESA responsiveness after 12\u00a0weeks, had a higher risk of malignancy than the good response group (adjusted HR: 2.01; 95% CI: 1.08\u20133.72).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both initial ESA hyporesponsiveness and subsequent declines in responsiveness were significantly associated with the development of malignancy in patients with NDD-CKD. ESA hyporesponsiveness may serve as a clinical marker that reflects an increased risk of undiagnosed malignancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10157-025-02769-7","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:19:30Z","timestamp":1761581970000},"page":"240-247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Erythropoiesis-stimulating agent hyporesponsiveness and malignancy development in patients with non-dialysis chronic kidney disease: a prospective cohort study"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-1900","authenticated-orcid":false,"given":"Nobuhiro","family":"Hashimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terumasa","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Kagimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiei","family":"Narita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"issue":"9","key":"2769_CR1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJM199808273390903","volume":"339","author":"A Besarab","year":"1998","unstructured":"Besarab A, Bolton WK, Browne JK, et al. 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NH and TK have declared no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Nagoya University: 2014\u20130027) and with the 1964 Helsinki Declaration and its later amendment or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}