{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:16:54Z","timestamp":1790662614678,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006484","name":"Vifor Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3\u20135 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients from Brazil (n\u2009=\u2009205), France (n\u2009=\u20092015) and the USA (n\u2009=\u2009293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013\u20132019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT\u2009\u226420% and ferritin \u2265300 or &amp;lt;50\u2009ng\/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TSAT\u2009\u226415% and ferritin &amp;lt;50\u2009ng\/mL and \u2265300\u2009ng\/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT\u2009\u226420% and ferritin &amp;lt;50 or \u2265300\u2009ng\/mL had lower functional status and worse PCS scores than those with a TSAT of 20\u201330% and ferritin 50\u2013299\u2009ng\/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfab050","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T15:25:13Z","timestamp":1614093913000},"page":"1694-1703","source":"Crossref","is-referenced-by-count":40,"title":["Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia"],"prefix":"10.1093","volume":"36","author":[{"given":"Murilo","family":"Guedes","sequence":"first","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"},{"name":"Pontificia Universidade Catolica do Parana, Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Muenz","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarcy","family":"Zee","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Barreto","family":"Lopes","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Waechter","sequence":"additional","affiliation":[{"name":"Vifor Pharma, Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Stengel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Universit\u00e9 Versailles Saint-Quentin-en-Yvelines, Universit\u00e9 Paris-Sud, Inserm, \u00c9quipe Epid\u00e9miologie Clinique, CESP, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad A","family":"Massy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Universit\u00e9 Versailles Saint-Quentin-en-Yvelines, Universit\u00e9 Paris-Sud, Inserm, \u00c9quipe Epid\u00e9miologie Clinique, CESP, Villejuif, France"},{"name":"Division of Nephrology, Ambroise Par\u00e9 University Hospital, APHP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-0051","authenticated-orcid":false,"given":"Elodie","family":"Speyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Universit\u00e9 Versailles Saint-Quentin-en-Yvelines, Universit\u00e9 Paris-Sud, Inserm, \u00c9quipe Epid\u00e9miologie Clinique, CESP, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Ayav","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Universit\u00e9 Versailles Saint-Quentin-en-Yvelines, Universit\u00e9 Paris-Sud, Inserm, \u00c9quipe Epid\u00e9miologie Clinique, CESP, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredric","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Sesso","sequence":"additional","affiliation":[{"name":"Federal University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L","family":"Pisoni","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M","family":"Robinson","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Pecoits-Filho","sequence":"additional","affiliation":[{"name":"Arbor Research Collaborative for Health, Ann Arbor, MI, USA"},{"name":"Pontificia Universidade Catolica do Parana, Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"2021082722460016600_gfab050-B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to tango: regulation of mammalian iron metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell"},{"key":"2021082722460016600_gfab050-B2","doi-asserted-by":"crossref","first-page":"568S","DOI":"10.1093\/jn\/131.2.568S","article-title":"Iron biology in immune function, muscle metabolism and neuronal functioning","volume":"131","author":"Beard","year":"2001","journal-title":"J Nutr"},{"key":"2021082722460016600_gfab050-B3","first-page":"279","article-title":"KDIGO clinical practice guideline for anemia in chronic kidney disease","volume":"2","year":"2012","journal-title":"Kidney Int Suppl"},{"key":"2021082722460016600_gfab050-B4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejim.2017.04.018","article-title":"Clinical management of iron deficiency anemia in adults: systemic review on advances in diagnosis and treatment","volume":"42","author":"De Franceschi","year":"2017","journal-title":"Eur J Intern Med"},{"key":"2021082722460016600_gfab050-B5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.semnephrol.2016.05.002","article-title":"Disorders of iron metabolism and anemia in chronic kidney disease","volume":"36","author":"Panwar","year":"2016","journal-title":"Semin Nephrol"},{"key":"2021082722460016600_gfab050-B6","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1681\/ASN.2019020213","article-title":"Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment","volume":"31","author":"Batchelor","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"2021082722460016600_gfab050-B7","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1053\/j.ajkd.2017.09.026","article-title":"Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018","volume":"71","author":"Fishbane","year":"2018","journal-title":"Am J Kidney Dis"},{"key":"2021082722460016600_gfab050-B8","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1093\/ndt\/gfp758","article-title":"Initiation of anaemia management in patients with chronic kidney disease not on dialysis in the Veterans Health Administration","volume":"25","author":"Lawler","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"2021082722460016600_gfab050-B9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/ckj\/sfz091","article-title":"Anemia and iron deficiency among chronic kidney disease Stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated","volume":"13","author":"Wong","year":"2019","journal-title":"Clin Kidney J"},{"key":"2021082722460016600_gfab050-B10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/00015385.2017.1351239","article-title":"Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction","volume":"73","author":"Martens","year":"2018","journal-title":"Acta Cardiol"},{"key":"2021082722460016600_gfab050-B11","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.cardfail.2011.08.003","article-title":"Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure","volume":"17","author":"Jankowska","year":"2011","journal-title":"J Card Fail"},{"key":"2021082722460016600_gfab050-B12","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1056\/NEJMoa0908355","article-title":"Ferric carboxymaltose in patients with heart failure and iron deficiency","volume":"361","author":"Anker","year":"2009","journal-title":"N Engl J Med"},{"key":"2021082722460016600_gfab050-B13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ejhf.823","article-title":"Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis","volume":"20","author":"Anker","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2021082722460016600_gfab050-B14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/ndt\/gfz192","article-title":"Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease","volume":"36","author":"Awan","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"2021082722460016600_gfab050-B15","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.kint.2019.04.029","article-title":"An increased mortality risk is associated with abnormal iron status in diabetic and non-diabetic veterans with predialysis chronic kidney disease","volume":"96","author":"Cho","year":"2019","journal-title":"Kid Int"},{"key":"2021082722460016600_gfab050-B16","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1093\/ndt\/gfu201","article-title":"FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia","volume":"29","author":"Macdougall","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"2021082722460016600_gfab050-B17","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1053\/j.ajkd.2016.04.018","article-title":"Intravenous versus oral iron supplementation for the treatment of anemia in CKD: an updated systematic review and meta-analysis","volume":"68","author":"Shepshelovich","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"2021082722460016600_gfab050-B18","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1053\/j.ajkd.2016.03.414","article-title":"The CKD Outcomes and Practice Patterns Study (CKDopps): rationale and methods","volume":"68","author":"Mariani","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"2021082722460016600_gfab050-B19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF00451725","article-title":"Development of the Kidney Disease Quality of Life (KDQOL) instrument","volume":"3","author":"Hays","year":"1994","journal-title":"Qual Life Res"},{"key":"2021082722460016600_gfab050-B20","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/00005650-199603000-00003","article-title":"A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity","volume":"34","author":"Ware","year":"1996","journal-title":"Med Care"},{"key":"2021082722460016600_gfab050-B21","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1123\/jpah.6.6.790","article-title":"Global Physical Activity Questionnaire (GPAQ): nine country reliability and validity study","volume":"6","author":"Bull","year":"2009","journal-title":"J Phys Act Health"},{"key":"2021082722460016600_gfab050-B22","volume-title":"Global Physical Activity Questionnaire (GPAQ) Analysis Guide","year":"2020"},{"key":"2021082722460016600_gfab050-B23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0749-3797(18)30622-6","article-title":"Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale)","volume":"10","author":"Andresen","year":"1994","journal-title":"Am J Prev Med"},{"key":"2021082722460016600_gfab050-B24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/geront\/10.1_Part_1.20","article-title":"Progress in development of the index of ADL","volume":"10","author":"Katz","year":"1970","journal-title":"Gerontologist"},{"key":"2021082722460016600_gfab050-B25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/geront\/9.3_Part_1.179","article-title":"Assessment of older people: self-maintaining and instrumental activities of daily living","volume":"9","author":"Lawton","year":"1969","journal-title":"Gerontologist"},{"key":"2021082722460016600_gfab050-B26","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1053\/j.ajkd.2015.09.024","article-title":"Functional dependence and mortality in the international Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"67","author":"Jassal","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"2021082722460016600_gfab050-B27","author":"Raghunathan","year":"2002"},{"key":"2021082722460016600_gfab050-B28","volume-title":"Multiple Imputation for Nonresponse in Surveys","author":"Rubin","year":"2004"},{"key":"2021082722460016600_gfab050-B29","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/ajh.24820","article-title":"Iron deficiency across chronic inflammatory conditions: international expert opinion on definition, diagnosis, and management","volume":"92","author":"Cappellini","year":"2017","journal-title":"Am J Hematol"},{"key":"2021082722460016600_gfab050-B30","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/S0140-6736(20)32339-4","article-title":"Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial","volume":"396","author":"Ponikowski","year":"2020","journal-title":"Lancet"},{"key":"2021082722460016600_gfab050-B31","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/ejhf.640","article-title":"Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis","volume":"19","author":"Melenovsky","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2021082722460016600_gfab050-B32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00392-018-1344-x","article-title":"Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life","volume":"108","author":"Bekfani","year":"2019","journal-title":"Clin Res Cardiol"},{"key":"2021082722460016600_gfab050-B33","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1001\/jama.2017.5427","article-title":"Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial","volume":"317","author":"Lewis","year":"2017","journal-title":"JAMA"},{"key":"2021082722460016600_gfab050-B34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/17474086.2016.1268047","article-title":"Mitochondria and Iron: current questions","volume":"10","author":"Paul","year":"2017","journal-title":"Expert Rev Hematol"},{"key":"2021082722460016600_gfab050-B35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12955-018-0933-8","article-title":"Measurement properties of the Short Form-36 (SF-36) and the Functional Assessment of Cancer Therapy\u2013Anemia (FACT-An) in patients with anemia associated with chronic kidney disease","volume":"16","author":"Finkelstein","year":"2018","journal-title":"Health Qual Life Outcomes"},{"key":"2021082722460016600_gfab050-B36","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0272-6386(04)01106-0","article-title":"Health-related quality of life in the Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"44","author":"Mapes","year":"2004","journal-title":"Am J Kidney Dis"},{"key":"2021082722460016600_gfab050-B37","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/ejhf.84","article-title":"The additive burden of iron deficiency in the cardiorenal\u2013anaemia axis: scope of a problem and its consequences","volume":"16","author":"Klip","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2021082722460016600_gfab050-B38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.7326\/M15-1839","article-title":"The effect of erythropoietin-stimulating agents on health-related quality of life in anemia of chronic kidney disease: a systematic review and meta-analysis","volume":"164","author":"Collister","year":"2016","journal-title":"Ann Intern Med"},{"key":"2021082722460016600_gfab050-B39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000362888","article-title":"Physiology of iron metabolism","volume":"41","author":"Waldvogel-Abramowski","year":"2014","journal-title":"Transfus Med Hemother"},{"key":"2021082722460016600_gfab050-B40","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1183\/09031936.00156410","article-title":"How important is a minimal difference?","volume":"37","author":"Troosters","year":"2011","journal-title":"Eur Respirat J"},{"key":"2021082722460016600_gfab050-B41","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1477-7525-4-70","article-title":"Responsiveness and minimal important differences for patient reported outcomes","volume":"4","author":"Revicki","year":"2006","journal-title":"Health Qual Life Outcomes"},{"key":"2021082722460016600_gfab050-B42","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/s41598-020-79254-6","article-title":"A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps","volume":"11","author":"Lopes","year":"2021","journal-title":"Sci Rep"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfab050\/36351749\/gfab050.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/36\/9\/1694\/40075888\/gfab050.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/36\/9\/1694\/40075888\/gfab050.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T18:47:29Z","timestamp":1630090049000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/36\/9\/1694\/6149131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,2,24]]},"published-print":{"date-parts":[[2021,8,27]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfab050","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,1]]},"published":{"date-parts":[[2021,2,24]]}}}