{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:05:36Z","timestamp":1785222336917,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CliCon S.r.l. Societ\u00e0 Benefit"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p &lt; 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245\u20ac vs. 9918\u20ac, p &lt; 0.001), mainly attributable to hospitalizations (3767\u20ac vs. 8486\u20ac, p &lt; 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients\u2019 clinical outcomes and healthcare cost savings.<\/jats:p>","DOI":"10.3390\/jcm11195820","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"5820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influence of Iron-Deficiency Anaemia (IDA) Therapy on Clinical Outcomes and Healthcare Resource Consumptions in Chronic Kidney Disease Patients Affected by IDA: A Real-Word Evidence Study among the Italian Population"],"prefix":"10.3390","volume":"11","author":[{"given":"Valentina","family":"Perrone","sequence":"first","affiliation":[{"name":"CliCon Societ\u00e0 Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-2022","authenticated-orcid":false,"given":"Chiara","family":"Veronesi","sequence":"additional","affiliation":[{"name":"CliCon Societ\u00e0 Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Dovizio","sequence":"additional","affiliation":[{"name":"CliCon Societ\u00e0 Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica Daniela","family":"Ancona","sequence":"additional","affiliation":[{"name":"Dipartimento Farmaceutico, Azienda Sanitaria Locale delle province di Barletta- Andria- Trani (BAT), 76125 Andria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Dipartimento Farmaceutico, Unit\u00e0 Sanitaria Locale Umbria 2, 05100 Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Dipartimento della Diagnostica ed Assistenza Farmaceutica, ASL Frosinone, 03100 Frosinone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-0449","authenticated-orcid":false,"given":"Alessandro","family":"Lupi","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale del Verbano Cusio Ossola (VCO), 28887 Omegna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Palcic","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), 34148 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Re","sequence":"additional","affiliation":[{"name":"Dipartimento Assistenza Territoriale, Azienda Sanitaria Locale di Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9160-5376","authenticated-orcid":false,"given":"Annamaria Pia","family":"Terlizzi","sequence":"additional","affiliation":[{"name":"Dipartimento Farmaceutico, Azienda Sanitaria Locale delle province di Barletta- Andria- Trani (BAT), 76125 Andria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ramirez de Arellano Serna","sequence":"additional","affiliation":[{"name":"CSL Vifor Group, 8152 Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cogliati","sequence":"additional","affiliation":[{"name":"CSL Vifor Italia, 00142 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Degli Esposti","sequence":"additional","affiliation":[{"name":"CliCon Societ\u00e0 Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","unstructured":"Kidney Disease Improving Global Outcomes (2012). KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease, KDIGO. Kidney International Supplements."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Stauffer, M.E., and Fan, T. (2014). Prevalence of anemia in chronic kidney disease in the United States. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084943"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/ndt\/11.supp2.125","article-title":"Nephrology dialysis transplantation quality of life in dialysis patients. A Spanish multicentre study","volume":"11","author":"Moreno","year":"1996","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1185\/030079906X132541","article-title":"Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa","volume":"22","author":"Lefebvre","year":"2006","journal-title":"Curr. Med. Res Opin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1093\/ndt\/gfs007","article-title":"DNL. Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients","volume":"27","author":"Minutolo","year":"2012","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ahj.2005.03.055","article-title":"Kidney function and anemia as risk factors for coronary heart disease and mortality: The atherosclerosis risk in communities (ARIC) study","volume":"151","author":"Astor","year":"2006","journal-title":"Am. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/sj.ki.5000105","article-title":"Association of anemia with outcomes in men with moderate and severe chronic kidney disease","volume":"69","author":"Kovesdy","year":"2006","journal-title":"Kidney Int."},{"key":"ref_8","first-page":"565","article-title":"Economic burden of anemia in an insured population","volume":"11","author":"Nissenson","year":"2005","journal-title":"J. Manag. Care Pharm."},{"key":"ref_9","unstructured":"(2012). Chapter 3, Use of ESAs and other agents to treat anemia in CKD. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease, KDIGO. Kidney International Supplements."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"642296","DOI":"10.3389\/fmed.2021.642296","article-title":"Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments to Future Agents","volume":"8","author":"Broseta","year":"2021","journal-title":"Front. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1681\/ASN.2011111078","article-title":"Mechanisms of anemia in CKD","volume":"23","author":"Babitt","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","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":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/ndt\/gft443","article-title":"The iron cycle in chronic kidney disease (CKD): From genetics and experimental models to CKD patients","volume":"29","author":"Babitt","year":"2014","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1093\/ndt\/gft533","article-title":"Haemoglobin levels and health-related quality of life in young and elderly patients on specialized predialysis care","volume":"29","author":"Meuleman","year":"2014","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1056\/NEJMoa0907845","article-title":"A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease","volume":"361","author":"Pfeffer","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/ki.2015.163","article-title":"A randomized trial of intravenous and oral iron in chronic kidney disease","volume":"88","author":"Agarwal","year":"2015","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1056\/NEJMoa065485","article-title":"Correction of anemia with epoetin alfa in chronic kidney disease","volume":"355","author":"Singh","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_18","unstructured":"National Institute for Health and Care Excellence [NICE] (2022, September 29). NICE Guideline (NG-8): Chronic Kidney Disease: Managing Anemia. Available online: https:\/\/www.nice.org.uk\/guidance\/ng8\/chapter\/1-Recommendations."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2215\/CJN.01670408","article-title":"Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988\u20132004","volume":"4","author":"Fishbane","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1093\/ndt\/gft033","article-title":"Kidney disease: Improving global outcomes guidelines on anaemia management in chronic kidney disease: A European Renal Best Practice position statement","volume":"28","author":"Locatelli","year":"2013","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_21","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."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7692376","DOI":"10.1155\/2020\/7692376","article-title":"The impact of CKD anaemia on patients: Incidence, risk factors, and clinical outcomes\u2014A systematic literature review","volume":"2020","author":"Palaka","year":"2020","journal-title":"Int. J. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1001\/archinte.164.6.659","article-title":"Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization","volume":"164","author":"Keith","year":"2004","journal-title":"Arch. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.semnephrol.2016.05.008","article-title":"The economic burden of chronic kidney disease and end-stage renal disease","volume":"36","author":"Wang","year":"2016","journal-title":"Semin. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3111\/13696998.2010.529032","article-title":"Healthcare costs associated with nephrology care in pre-dialysis chronic kidney disease patients","volume":"13","author":"Ekeman","year":"2010","journal-title":"J. Med. Econ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/13696998.2019.1588738","article-title":"Economic and quality of life burden of anemia on patients with CKD on dialysis: A systematic review","volume":"22","author":"Spinowitz","year":"2019","journal-title":"J. Med. Econ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s41669-019-0132-5","article-title":"Economic Burden and Health-Related Quality of Life Associated with Current Treatments for Anaemia in Patients with CKD not on Dialysis: A Systematic Review","volume":"3","author":"Pergola","year":"2019","journal-title":"PharmacoEcon. Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/OLQ.0000000000000635","article-title":"An Illustration of Errors in Using the P Value to Indicate Clinical Significance or Epidemiological Importance of a Study Finding","volume":"44","author":"Kang","year":"2017","journal-title":"Sex Transm. Dis."},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s40620-019-00652-9","article-title":"Anemia and clinical outcomes in patients with non-dialysis dependent or dialysis dependent severe chronic kidney disease: A Danish population-based study","volume":"33","author":"Toft","year":"2020","journal-title":"J. Nephrol."},{"key":"ref_31","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":"Kidney Int."},{"key":"ref_32","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":"2021","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1161\/CIRCULATIONAHA.105.577577","article-title":"Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: The Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study","volume":"113","author":"Go","year":"2006","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1681\/ASN.2004080656","article-title":"Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease: Results from the atherosclerosis risk in communities study","volume":"16","author":"Muntner","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1097\/01.ASN.0000092138.65211.71","article-title":"Association of high serum creatinine and anemia increases the risk of coronary events: Results from the prospective community-based atherosclerosis risk in communities (ARIC) study","volume":"14","author":"Jurkovitz","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.amjmed.2019.02.018","article-title":"Iron supplementation improves cardiovascular outcomes in patients with heart failure","volume":"132","author":"Zhou","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_37","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":"ref_38","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":"ref_39","doi-asserted-by":"crossref","unstructured":"Hung, N., Shen, C.-C., Hu, Y.-W., Hu, L.-Y., Yeh, C.-M., Teng, C.-J., Kuan, A.-S., Chen, S.-C., Chen, T.-J., and Liu, C.-J. (2015). Risk of Cancer in Patients with Iron Deficiency Anemia: A Nationwide Population-Based Study. PLoS ONE, 10, reprinted in PLoS ONE 2015, 10, e0125951.","DOI":"10.1371\/journal.pone.0125951"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1016\/S0140-6736(09)60502-X","article-title":"Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: A meta-analysis of randomised trials","volume":"373","author":"Bohlius","year":"2009","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"A7","DOI":"10.1053\/j.ajkd.2016.12.004","article-title":"US Renal Data System 2016 Annual Data Report: Epidemiology of Kidney Disease in the United States","volume":"69","author":"Saran","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1056\/NEJMc1602469","article-title":"Trends in Chronic Kidney Disease in China","volume":"375","author":"Zhang","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrneph.2013.146","article-title":"Nephrology in China","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1523-1755.2002.00432.x","article-title":"Health care utilization among patients with chronic kidney disease","volume":"62","author":"Khan","year":"2002","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1097\/01.ASN.0000125670.64996.BB","article-title":"Cost of medical care for chronic kidney disease and comorbidity among enrollees in a large HMO population","volume":"15","author":"Smith","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_46","unstructured":"(2013). Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl., 3, 4477\u20134483."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/19\/5820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:38Z","timestamp":1760143478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/19\/5820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["jcm11195820"],"URL":"https:\/\/doi.org\/10.3390\/jcm11195820","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}