{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:12:09Z","timestamp":1792588329583,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100006484","name":"Vifor-Fresenius Medical Care Renal Pharma Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004702","name":"Baxter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp & Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Lilly","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006484","name":"Vifor Fresenius","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi-Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Management of iron deficiency in patients with nondialysis CKD focuses on improving erythropoiesis. Studies in patients with heart failure with similar iron deficiency pathogenesis found that treating iron deficiency improves cardiovascular outcomes, regardless of anemia. To evaluate a possible anemia-independent association of iron stores with outcomes in individuals with nondialysis CKD, the authors studied patients in nephrology-based clinics from a multinational cohort. They show that iron deficiency, as reflected by transferrin saturation index, is associated with higher risk of mortality and cardiovascular events in patients with CKD, with or without anemia. Intervention studies addressing the effects of treating iron deficiency beyond effects on erythropoiesis are necessary to challenge the current anemia-focused paradigm of iron deficiency management in nondialysis CKD, and potentially foster better strategies for improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 30%\u201345% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with patients with a TSAT of 26%\u201335%, those with a TSAT \u226415% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT \u226546%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin \u2265300 ng\/ml.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020101531","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T12:35:24Z","timestamp":1625747724000},"page":"2020-2030","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia"],"prefix":"10.1681","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-852X","authenticated-orcid":false,"given":"Murilo","family":"Guedes","sequence":"first","affiliation":[{"name":"Pontificia Universidade Catolica do Parana, Curitiba, Brazil"},{"name":"Arbor 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A.","family":"Massy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Saclay, Villejuif, France"},{"name":"Service de N\u00e9phrologie et Dialyse, Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Universitaire Ambroise Par\u00e9, Boulogne Billancourt, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Mansencal","sequence":"additional","affiliation":[{"name":"Service de Cardiologie Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Universitaire Ambroise Par\u00e9, Boulogne Billancourt, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.Y.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7695-3583","authenticated-orcid":false,"given":"David 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