{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T22:49:34Z","timestamp":1775688574732,"version":"3.50.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Astellas Pharma, Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2024,4]]},"DOI":"10.1007\/s12325-023-02727-3","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T09:02:54Z","timestamp":1708074174000},"page":"1526-1552","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase\u00a03 Roxadustat Trials in Japan"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-9106","authenticated-orcid":false,"given":"Takayuki","family":"Hamano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-5303","authenticated-orcid":false,"given":"Yusuke","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kashia","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4064-4528","authenticated-orcid":false,"given":"Sho","family":"Mizokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-9328","authenticated-orcid":false,"given":"Yuichiro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Dellanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-7229","authenticated-orcid":false,"given":"Jonathan","family":"Barratt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6150-9201","authenticated-orcid":false,"given":"Tadao","family":"Akizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"issue":"8","key":"2727_CR1","doi-asserted-by":"publisher","first-page":"613","DOI":"10.3949\/ccjm.83a.15065","volume":"83","author":"G Nakhoul","year":"2016","unstructured":"Nakhoul G, Simon JF. Anemia of chronic kidney disease: treat it, but not too aggressively. Cleve Clin J Med. 2016;83(8):613\u201324.","journal-title":"Cleve Clin J Med"},{"issue":"3","key":"2727_CR2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000455166","volume":"45","author":"F Locatelli","year":"2017","unstructured":"Locatelli F, Fishbane S, Block GA, Macdougall IC. Targeting hypoxia-inducible factors for the treatment of anemia in chronic kidney disease patients. Am J Nephrol. 2017;45(3):187\u201399.","journal-title":"Am J Nephrol"},{"issue":"1","key":"2727_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/ndt\/gft209","volume":"29","author":"J Lutz","year":"2014","unstructured":"Lutz J, Menke J, Sollinger D, Schinzel H, Thurmel K. Haemostasis in chronic kidney disease. Nephrol Dial Transplant. 2014;29(1):29\u201340.","journal-title":"Nephrol Dial Transplant"},{"key":"2727_CR4","doi-asserted-by":"crossref","unstructured":"Yamamoto H, Nishi S, Tomo T, et al. 2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease. Ren Replace Ther. 2017;3(1).","DOI":"10.1186\/s41100-017-0114-y"},{"issue":"8","key":"2727_CR5","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1080\/14740338.2016.1182494","volume":"15","author":"L Del Vecchio","year":"2016","unstructured":"Del Vecchio L, Locatelli F. An overview on safety issues related to erythropoiesis-stimulating agents for the treatment of anaemia in patients with chronic kidney disease. Expert Opin Drug Saf. 2016;15(8):1021\u201330.","journal-title":"Expert Opin Drug Saf"},{"issue":"2","key":"2727_CR6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/1744-9987.12888","volume":"24","author":"T Akizawa","year":"2020","unstructured":"Akizawa T, Otsuka T, Reusch M, Ueno M. Intermittent oral dosing of roxadustat in peritoneal dialysis chronic kidney disease patients with anemia: a randomized, phase\u00a03, multicenter, open-label study. Ther Apher Dial. 2020;24(2):115\u201325.","journal-title":"Ther Apher Dial"},{"issue":"7","key":"2727_CR7","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1681\/ASN.2019060623","volume":"31","author":"T Akizawa","year":"2020","unstructured":"Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase\u00a03, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan. J Am Soc Nephrol. 2020;31(7):1628\u201339.","journal-title":"J Am Soc Nephrol"},{"issue":"10","key":"2727_CR8","doi-asserted-by":"publisher","first-page":"5345","DOI":"10.1007\/s12325-021-01903-7","volume":"38","author":"J Barratt","year":"2021","unstructured":"Barratt J, Sulowicz W, Schomig M, et al. Efficacy and cardiovascular safety of roxadustat in dialysis-dependent chronic kidney disease: pooled analysis of four phase\u00a03 studies. Adv Ther. 2021;38(10):5345\u201360.","journal-title":"Adv Ther"},{"key":"2727_CR9","unstructured":"Pharmaceuticals and Medical Devices Agency (Japan). Report on the deliberation results\u2013Evrenzo (roxadustat). September 2019."},{"issue":"4","key":"2727_CR10","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1111\/jcpt.13385","volume":"46","author":"H Chen","year":"2021","unstructured":"Chen H, Cheng Q, Wang J, Zhao X, Zhu S. Long-term efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in anaemia of chronic kidney disease: a meta-analysis including 13,146 patients. J Clin Pharm Ther. 2021;46(4):999\u20131009.","journal-title":"J Clin Pharm Ther"},{"issue":"6","key":"2727_CR11","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1111\/1744-9987.13468","volume":"24","author":"T Akizawa","year":"2020","unstructured":"Akizawa T, Ueno M, Shiga T, Reusch M. Oral roxadustat three times weekly in ESA-naive and ESA-converted patients with anemia of chronic kidney disease on hemodialysis: results from two phase\u00a03 studies. Ther Apher Dial. 2020;24(6):628\u201341.","journal-title":"Ther Apher Dial"},{"issue":"5","key":"2727_CR12","first-page":"874","volume":"33","author":"AO Molnar","year":"2018","unstructured":"Molnar AO, Bota SE, McArthur E, et al. Risk and complications of venous thromboembolism in dialysis patients. Nephrol Dial Transplant. 2018;33(5):874\u201380.","journal-title":"Nephrol Dial Transplant"},{"key":"2727_CR13","doi-asserted-by":"publisher","first-page":"I9","DOI":"10.1161\/01.CIR.0000078469.07362.E6","volume":"107","author":"F Anderson","year":"2003","unstructured":"Anderson F. Risk factors for venous thromboembolism. Circulation. 2003;107:I9\u201316.","journal-title":"Circulation"},{"issue":"1","key":"2727_CR14","doi-asserted-by":"publisher","first-page":"10720","DOI":"10.1038\/s41598-019-47293-3","volume":"9","author":"MY Hsieh","year":"2019","unstructured":"Hsieh MY, Lee CK, Lo CM, Chen CH, Chuang SY, Wu CC. Temporal distribution and biological determinants of thrombotic events after interventions for dialysis vascular access. Sci Rep. 2019;9(1):10720.","journal-title":"Sci Rep"},{"issue":"4","key":"2727_CR15","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1097\/MBC.0000000000000249","volume":"26","author":"SH Hung","year":"2015","unstructured":"Hung SH, Lin HC, Chung SD. Association between venous thromboembolism and iron-deficiency anemia: a population-based study. Blood Coagul Fibrinolysis. 2015;26(4):368\u201372.","journal-title":"Blood Coagul Fibrinolysis"},{"key":"2727_CR16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1161\/STROKEAHA.114.007486","volume":"46","author":"JM Coutinho","year":"2015","unstructured":"Coutinho JM. Association between anemia and cerebral venous thrombosis. Stroke. 2015;46:5.","journal-title":"Stroke"},{"issue":"5","key":"2727_CR17","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1161\/CIRCRESAHA.119.316453","volume":"127","author":"X Tang","year":"2020","unstructured":"Tang X, Fang M, Cheng R, et al. Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability. Circ Res. 2020;127(5):651\u201363.","journal-title":"Circ Res"},{"issue":"3","key":"2727_CR18","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/ajh.22262","volume":"87","author":"DH Henry","year":"2012","unstructured":"Henry DH, Dahl NV, Auerbach MA. Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron. Am J Hematol. 2012;87(3):308\u201310.","journal-title":"Am J Hematol"},{"issue":"8","key":"2727_CR19","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1681\/ASN.2020101531","volume":"32","author":"M Guedes","year":"2021","unstructured":"Guedes M, Muenz DG, Zee J, et al. 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. J Am Soc Nephrol. 2021;32(8):2020\u201330.","journal-title":"J Am Soc Nephrol"},{"issue":"9","key":"2727_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0236277","volume":"15","author":"T Kuragano","year":"2020","unstructured":"Kuragano T, Joki N, Hase H, et al. Low transferrin saturation (TSAT) and high ferritin levels are significant predictors for cerebrovascular and cardiovascular disease and death in maintenance hemodialysis patients. PLoS One. 2020;15(9):e0236277.","journal-title":"PLoS ONE"},{"issue":"1","key":"2727_CR21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12882-018-1021-3","volume":"19","author":"MF Eisenga","year":"2018","unstructured":"Eisenga MF, Nolte IM, van der Meer P, Bakker SJL, Gaillard C. Association of different iron deficiency cutoffs with adverse outcomes in chronic kidney disease. BMC Nephrol. 2018;19(1):225.","journal-title":"BMC Nephrol"},{"issue":"1","key":"2727_CR22","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1093\/ndt\/gfz192","volume":"36","author":"AA Awan","year":"2021","unstructured":"Awan AA, Walther CP, Richardson PA, Shah M, Winkelmayer WC, Navaneethan SD. Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease. Nephrol Dial Transplant. 2021;36(1):129\u201336.","journal-title":"Nephrol Dial Transplant"},{"issue":"12","key":"2727_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082952","volume":"8","author":"YL Chang","year":"2013","unstructured":"Chang YL, Hung SH, Ling W, Lin HC, Li HC, Chung SD. Association between ischemic stroke and iron-deficiency anemia: a population-based study. PLoS One. 2013;8(12):e82952.","journal-title":"PLoS one"},{"issue":"15","key":"2727_CR24","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.009206","volume":"7","author":"KL Kuo","year":"2018","unstructured":"Kuo KL, Hung SC, Tseng WC, et al. Association of anemia and iron parameters with mortality among patients undergoing prevalent hemodialysis in Taiwan: the AIM-HD study. J Am Heart Assoc. 2018;7(15):e009206.","journal-title":"J Am Heart Assoc"},{"issue":"8","key":"2727_CR25","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1002\/hep4.2012","volume":"6","author":"CC Hsu","year":"2022","unstructured":"Hsu CC, Senussi NH, Fertrin KY, Kowdley KV. Iron overload disorders. Hepatol Commun. 2022;6(8):1842\u201354.","journal-title":"Hepatol Commun"},{"issue":"3","key":"2727_CR26","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.xkme.2020.01.006","volume":"2","author":"T Ganz","year":"2020","unstructured":"Ganz T. Iron administration, infection, and anemia management in CKD: untangling the effects of intravenous iron therapy on immunity and infection risk. Kidney Med. 2020;2(3):341\u201353.","journal-title":"Kidney Med"},{"issue":"5","key":"2727_CR27","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1056\/NEJMoa1810742","volume":"380","author":"IC Macdougall","year":"2019","unstructured":"Macdougall IC, White C, Anker SD, et al. Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med. 2019;380(5):447\u201358.","journal-title":"N Engl J Med"},{"issue":"1","key":"2727_CR28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2215\/CJN.01170905","volume":"2","author":"BD Bradbury","year":"2007","unstructured":"Bradbury BD, Fissell RB, Albert JM, et al. Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2007;2(1):89\u201399.","journal-title":"Clin J Am Soc Nephrol"},{"key":"2727_CR29","doi-asserted-by":"publisher","first-page":"205435811666912","DOI":"10.1177\/2054358116669126","volume":"3","author":"JM MacRae","year":"2016","unstructured":"MacRae JM, Dipchand C, Oliver M, et al. Arteriovenous access failure, stenosis, and thrombosis. Can J Kidney Health Dis. 2016;3:2054358116669126.","journal-title":"Can J Kidney Health Dis"},{"issue":"6","key":"2727_CR30","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.18632\/aging.204611","volume":"15","author":"J Chen","year":"2023","unstructured":"Chen J, Shou X, Xu Y, et al. A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease. Aging. 2023;15(6):2237\u201374.","journal-title":"Aging"},{"issue":"1","key":"2727_CR31","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3324\/haematol.2013.083840","volume":"99","author":"SM Rezende","year":"2014","unstructured":"Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter SC. Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk. Haematologica. 2014;99(1):194\u2013200.","journal-title":"Haematologica"},{"issue":"9","key":"2727_CR32","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJM199808273390903","volume":"339","author":"A Besarab","year":"1998","unstructured":"Besarab A. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339(9):584\u201390.","journal-title":"N Engl J Med"},{"issue":"20","key":"2727_CR33","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1056\/NEJMoa062276","volume":"355","author":"TB Drueke","year":"2006","unstructured":"Drueke TB. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071\u201384.","journal-title":"N Engl J Med"},{"issue":"6","key":"2727_CR34","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/ki.2008.295","volume":"74","author":"LA Szczech","year":"2008","unstructured":"Szczech LA, Barnhart HX, Inrig JK, et al. Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int. 2008;74(6):791\u20138.","journal-title":"Kidney Int"},{"issue":"4","key":"2727_CR35","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.jflm.2008.08.015","volume":"16","author":"J Lucena","year":"2009","unstructured":"Lucena J, Rico A, V\u00e1zquez R, et al. Pulmonary embolism and sudden\u2013unexpected death: prospective study on 2477 forensic autopsies performed at the Institute of Legal Medicine in Seville. J Forensic Leg Med. 2009;16(4):196\u2013201.","journal-title":"J Forensic Leg Med"},{"issue":"Suppl 3","key":"2727_CR36","doi-asserted-by":"publisher","first-page":"S299","DOI":"10.21037\/cdt.2017.09.08","volume":"7","author":"KB Quencer","year":"2017","unstructured":"Quencer KB, Oklu R. Hemodialysis access thrombosis. Cardiovasc Diagn Ther. 2017;7(Suppl 3):S299\u2013308.","journal-title":"Cardiovasc Diagn Ther"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-023-02727-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-023-02727-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-023-02727-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T09:35:10Z","timestamp":1711186510000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-023-02727-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,16]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["2727"],"URL":"https:\/\/doi.org\/10.1007\/s12325-023-02727-3","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,16]]},"assertion":[{"value":"7 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Takayuki Hamano has received grants for physician-initiated research, consulting fees, and honoraria for lectures from Astellas Pharma, Inc. Yusuke Yamaguchi is an employee of Astellas Pharma, Inc. Kashia Goto has participated in company stock ownership plan through Astellas Pharma, Inc. Sho Mizokawa is an employee of Astellas Pharma, Inc. Yuichiro Ito is an employee of Astellas Pharma, Inc. Frank Dellanna has nothing to disclose. Jonathan Barratt has received fees for invited lectures from Astellas Pharma Inc. Tadao Akizawa has received personal consulting fees from Astellas Pharma, Inc., Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Fuso Pharmaceutical, Torii Pharmaceutical, GlaxoSmithKline, JT Pharmaceutical, Nipro Corporation, Otsuka, Sanwa Kagaku, and Bayer and has also received personal payment or honoraria for lectures from Astellas Pharma, Inc., Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Fuso Pharmaceutical, Torii Pharmaceutical, Chugai Pharmaceutical, Mitsubishi Tanabe, and Bayer.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All studies included in this post hoc analysis were conducted in accordance with the ethical principles of the Declaration of Helsinki of 1964 and its later amendments, the International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines, Good Clinical Practice, and applicable local laws and regulations. As this was a pooled post hoc analysis, approval by an ethics committee for this analysis was not necessary; however, institutional review board approval was obtained prior to initiating each of the studies. All participants provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}