{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:24:08Z","timestamp":1791357848202,"version":"4.3.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Nephrol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In the advanced stages of chronic kidney disease (CKD), anemia impacts 78.9% to 96.5% of patients. Darbepoetin is utilized for the treatment of anemia associated with chronic kidney disease (CKD). The function of darbepoetin alfa can be clarified by comparing it with other agents. A comprehensive review and network meta-analysis were conducted to assess the safety and efficacy of Darbepoetin alfa compared to other agents in the treatment of anemia associated with chronic kidney disease (CKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and network meta-analysis were conducted adhering to PRISMA-NMA guidelines. A systematic search was performed in databases Medline, Embase, and Scopus from inception to November 24, 2024, without language limitations. Randomized controlled trials assessing erythropoietin-stimulating agents (ESAs) or placebo in adults with chronic kidney disease (CKD)-related anemia were included. Data extraction and risk of bias assessment (RoB 2.0) were performed separately. Bayesian network meta-analysis using random-effects models was carried out using BUGSnet in R. Treatment effects were measured as odds ratios (ORs) or mean differences (MDs) with 95% credible intervals. Heterogeneity, inconsistency, and publication bias were evaluated, and certainty of evidence was assessed using the GRADE approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this network meta-analysis of 21 randomized trials involving over 4,000 CKD patients with anemia, Methoxy polyethylene glycol-epoetin beta showed the greatest hemoglobin increase, while Molidustat demonstrated the best cardiovascular and thrombotic safety despite lower efficacy. Daprodustat provided moderate hemoglobin improvement with a safety profile comparable to darbepoetin, showing no significant differences in mortality or cardiovascular events. Transferrin saturation, hypertension, and diabetes-related adverse events did not differ significantly across treatments. Roxadustat was associated with a higher incidence of gastrointestinal adverse events, particularly diarrhea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Daprodustat and roxadustat indicated equivalent or higher efficacy when compared to darbepoetin in elevating hemoglobin levels in CKD-related anemia, with daprodustat demonstrating a good safety profile. While conventional ESAs remain beneficial, HIF-PHIs offer promising oral alternatives with possible benefits in cardiovascular safety and decreased hypertension risk. Further head-to-head trials are necessary to confirm these findings and guide individualized treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12882-025-04557-7","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T20:56:07Z","timestamp":1763412967000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative effectiveness of darbepoetin vs other agents in chronic kidney disease-related anemia: a systematic review and network meta-analysis"],"prefix":"10.1186","volume":"26","author":[{"given":"Muhammad Faique","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Shaheer","family":"Bin Faheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamikha","family":"Cheema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathimathul","family":"Henna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Javid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rafiqul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insha","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousif Hameed","family":"Kurmasha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaya","family":"Samadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqub Nadeem","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"4557_CR1","doi-asserted-by":"publisher","first-page":"5248","DOI":"10.1182\/blood-2024-212360","volume":"144","author":"S Sharma","year":"2024","unstructured":"Sharma S, Modi S, Gadhiya D, Syed S, Jain H, Lakkimsetti M, Dharia AA, Patel D, Munnangi P, Patel VM, Patel J. Global burden and trend of anemia due to chronic kidney disease in G20 countries from 1990-2021. A benchmarking systematic analysis. Blood. 2024, Nov, 5;144:5248.","journal-title":"Blood"},{"key":"4557_CR2","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/jch.12560","volume":"17","author":"D Campbell","year":"2015","unstructured":"Campbell D, Weir MR. Defining, treating, and understanding chronic kidney disease-a complex disorder. J Clin Hypertens (greenwich). 2015;17:514\u201327. 6. Fishbane, S, Spinowitz, B. Update on Anemia in ESRD and earlier stages of CKD: Core curriculum 2018. Am J Kidney Dis. 2018(71):423-35.","journal-title":"J Clin Hypertens (greenwich)"},{"key":"4557_CR3","volume-title":"Atlas of CKD & ESRD","author":"U.S. Renal Data System -2012","year":"2012","unstructured":"U.S. Renal Data System -2012. Atlas of CKD & ESRD. 2012."},{"key":"4557_CR4","doi-asserted-by":"crossref","unstructured":"Lv JC, Zhang LX. Prevalence and disease burden of chronic kidney disease. Renal fibrosis: mechanisms and therapies. 2019;3\u201315.","DOI":"10.1007\/978-981-13-8871-2_1"},{"key":"4557_CR5","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","volume":"380","author":"R Lozano","year":"2012","unstructured":"Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2095\u2013128.","journal-title":"Lancet"},{"key":"4557_CR6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1471-2369-13-10","volume":"13","author":"MM Rajapurkar","year":"2012","unstructured":"Rajapurkar MM, John GT, Kirpalani AL, Abraham G, Agarwal SK, Almeida AF, et al. What do we know about chronic kidney disease in India: first report of the Indian CKD registry. BMC Nephrol. 2012;13:10.","journal-title":"BMC Nephrol"},{"key":"4557_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1056\/NEJM198701083160203","volume":"316","author":"JW Eschbach","year":"1987","unstructured":"Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin: results of a combined phase I and II clinical trial. N Engl J Med. 1987;316:73\u201378.","journal-title":"N Engl J Med"},{"key":"4557_CR8","doi-asserted-by":"publisher","first-page":"992","DOI":"10.7326\/0003-4819-111-12-992","volume":"111","author":"JW Eschbach","year":"1989","unstructured":"Eschbach JW, Abdulhadi MH, Browne JK, et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease: results of a phase III multicenter clinical trial. Ann Intern Med. 1989;111:992\u20131000.","journal-title":"Ann Intern Med"},{"key":"4557_CR9","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/S0735-1097(01)01470-X","volume":"38","author":"A Al-Ahmad","year":"2001","unstructured":"Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001;38:955\u201362.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"4557_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1053\/j.ajkd.2014.12.012","volume":"66","author":"ER Wilhelm-Leen","year":"2015","unstructured":"Wilhelm-Leen ER, Winkelmayer WC. Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis. Am J Kidney Dis. 2015, Jul, 1;66(1):69\u201374.","journal-title":"Am J Kidney Dis"},{"issue":"2","key":"4557_CR11","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s11255-022-03316-z","volume":"55","author":"Q Huang","year":"2023","unstructured":"Huang Q, Liao Z, Liu X, Xia Y, Wang J. Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis. Int Urology Nephrol. 2023, Feb;55(2):325\u201334.","journal-title":"Int Urology Nephrol"},{"key":"4557_CR12","doi-asserted-by":"publisher","first-page":"777","DOI":"10.7326\/M14-2385","volume":"162","author":"B Hutton","year":"2015","unstructured":"Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777\u201384. https:\/\/doi.org\/10.7326\/M14-2385.","journal-title":"Ann Intern Med"},{"issue":"7289","key":"4557_CR13","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JPT Higgins","year":"2011","unstructured":"Higgins JPT, Altman DG, G\u00f8tzsche PC, et al. The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ. 2011;343(7289):d5928. https:\/\/doi.org\/10.1136\/bmj.d5928.","journal-title":"BMJ"},{"key":"4557_CR14","doi-asserted-by":"publisher","first-page":"105020","DOI":"10.1016\/j.phrs.2020.105020","volume":"159","author":"Q Zheng","year":"2020","unstructured":"Zheng Q, Yang H, Sun L, Wei R, Fu X, Wang Y, Huang Y, Liu YN, Liu WJ. Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: a network meta-analysis. Pharmacol Res. 2020;159:105020. https:\/\/doi.org\/10.1016\/j.phrs.2020.105020.","journal-title":"Pharmacol Res"},{"issue":"6","key":"4557_CR15","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1001\/jamainternmed.2022.0605","volume":"182","author":"AK Singh","year":"2022","unstructured":"Singh AK, Cizman B, Carroll K, McMurray JJV, Perkovic V, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Wiecek A, Stankus N, Strutz F, Blackorby A, Cobitz AR, Meadowcroft AM, Paul G, \u2026 Solomon S. Efficacy and safety of daprodustat for treatment of anemia of chronic kidney disease in incident dialysis patients: a randomized clinical trial. JAMA Intern Med. 2022;182(6):592\u2013602. https:\/\/doi.org\/10.1001\/jamainternmed.2022.0605.","journal-title":"JAMA Intern Med"},{"issue":"11","key":"4557_CR16","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1056\/NEJMoa1813599","volume":"381","author":"N Chen","year":"2019","unstructured":"Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, Tao Y, Liang X, Liu Z, Xing C, Chen J, Luo L, Zuo L, Liao Y, Liu BC, Leong R, Wang C, Liu C, Neff T, Szczech L, \u2026 Yu KP. Roxadustat for anemia in patients with kidney disease not receiving dialysis. NEJM Evid. 2019;381(11):1001\u201310. https:\/\/doi.org\/10.1056\/NEJMoa1813599.","journal-title":"NEJM Evid"},{"issue":"1","key":"4557_CR17","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.kisu.2020.12.003","volume":"11","author":"AK Agarwal","year":"2021","unstructured":"Agarwal AK. Iron metabolism and management: focus on chronic kidney disease. Kidney Int Suppl. 2021;11(1):46\u201358. https:\/\/doi.org\/10.1016\/j.kisu.2020.12.003.","journal-title":"Kidney Int Suppl"},{"issue":"17","key":"4557_CR18","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMoa2035938","volume":"384","author":"GM Chertow","year":"2021","unstructured":"Chertow GM, Pergola PE, Farag YMK, Agarwal R, Arnold S, Bako G, Block GA, Burke S, Castillo FP, Jardine AG, Khawaja Z, Koury MJ, Lewis EF, Lin T, Luo W, Maroni BJ, Matsushita K, McCullough PA, Parfrey PS, Roy-Chaudhury P \u2026 PRO2TECT Study Group. Vadadustat in patients with anemia and non-dialysis-dependent CKD. NEJM Evid. 2021;384(17):1589\u2013600. https:\/\/doi.org\/10.1056\/NEJMoa2035938.","journal-title":"NEJM Evid"},{"issue":"10","key":"4557_CR19","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, Sch\u00f6mig M, Esposito C, Reusch M, Young J, Csiky B. Efficacy and cardiovascular safety of roxadustat in dialysis-dependent chronic kidney disease: pooled analysis of four phase 3 studies. Adv Ther. 2021;38(10):5345\u201360. https:\/\/doi.org\/10.1007\/s12325-021-01903-7.","journal-title":"Adv Ther"},{"issue":"1","key":"4557_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.blre.2012.12.003","volume":"27","author":"HV H","year":"2013","unstructured":"H HV. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev. 2013;27(1):41\u201353. https:\/\/doi.org\/10.1016\/j.blre.2012.12.003.","journal-title":"Blood Rev"},{"issue":"4","key":"4557_CR21","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1007\/s12325-023-02727-3","volume":"41","author":"T Hamano","year":"2024","unstructured":"Hamano T, Yamaguchi Y, Goto K, Mizokawa S, Ito Y, Dellanna F, Barratt J, Akizawa T. Risk factors for thromboembolic events in patients with dialysis-dependent CKD: pooled analysis of phase 3 roxadustat trials in Japan. Adv Ther. 2024;41(4):1526\u201352. https:\/\/doi.org\/10.1007\/s12325-023-02727-3.","journal-title":"Adv Ther"},{"key":"4557_CR22","unstructured":"FibroGen. Roxadustat approved in Japan for the treatment of anemia of chronic kidney disease in adult patients on dialysis [press release]. San Francisco (CA): FibroGen, Inc; 2019 Sep 20. Available from: investor.fibrogen.com\/news-releases\/news-release-details\/roxadustat-approved-japan-treatment-anemia-associated-chronic?"},{"key":"4557_CR23","unstructured":"Aetna. Daprodustat (Jesduvroq) - medical clinical policy bulletin: anemia of CKD in adults on dialysis. 2023 Feb. [cited 2025 Jan 2]. Available from: https:\/\/www.aetna.com\/cpb\/medical\/data\/1000_1099\/1044.html?."}],"container-title":["BMC Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-025-04557-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12882-025-04557-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-025-04557-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T20:56:13Z","timestamp":1763412973000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcnephrol.biomedcentral.com\/articles\/10.1186\/s12882-025-04557-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4557"],"URL":"https:\/\/doi.org\/10.1186\/s12882-025-04557-7","relation":{},"ISSN":["1471-2369"],"issn-type":[{"value":"1471-2369","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"assertion":[{"value":"20 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"641"}}