{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:19:06Z","timestamp":1789791546214,"version":"4.0.1"},"reference-count":43,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009010","name":"Novartis Pharmaceuticals UK Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018787","name":"Novartis Pharma AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","award":["GPP 2022"],"award-info":[{"award-number":["GPP 2022"]}],"id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["kireports.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International Reports"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1016\/j.ekir.2023.04.029","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T20:38:03Z","timestamp":1682800683000},"page":"1332-1341","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"title":["Design and Rationale of the APPELHUS Phase 3 Open-Label Study of Factor B Inhibitor Iptacopan for Atypical Hemolytic Uremic Syndrome"],"prefix":"10.1016","volume":"8","author":[{"given":"David","family":"Kavanagh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A.","family":"Greenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Bagga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshri G.","family":"Karki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajita","family":"Vasudevan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Charney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Dahlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Fakhouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ekir.2023.04.029_bib1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.kint.2018.02.029","article-title":"Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome","volume":"94","author":"Schaefer","year":"2018","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2023.04.029_bib2","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMra0902814","article-title":"Atypical hemolytic-uremic syndrome","volume":"361","author":"Noris","year":"2009","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ekir.2023.04.029_bib3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.kint.2016.10.005","article-title":"Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a \u201cKidney Disease: improving Global Outcomes\u201d (KDIGO) Controversies Conference","volume":"91","author":"Goodship","year":"2017","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2023.04.029_bib4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1182\/asheducation-2016.1.217","article-title":"Atypical hemolytic uremic syndrome","volume":"2016","author":"Afshar-Kharghan","year":"2016","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"10.1016\/j.ekir.2023.04.029_bib5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2147\/CLEP.S245642","article-title":"Epidemiology of atypical hemolytic uremic syndrome: a systematic literature review","volume":"12","author":"Yan","year":"2020","journal-title":"Clin Epidemiol"},{"key":"10.1016\/j.ekir.2023.04.029_bib6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00281-017-0663-8","article-title":"Diseases of complement dysregulation\u2014an overview","volume":"40","author":"Wong","year":"2018","journal-title":"Semin Immunopathol"},{"key":"10.1016\/j.ekir.2023.04.029_bib7","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype","volume":"5","author":"Noris","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib8","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2215\/CJN.04760512","article-title":"Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults","volume":"8","author":"Fremeaux-Bacchi","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib9","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3389\/fimmu.2019.00504","article-title":"The emerging role of complement proteins as a target for therapy of IgA nephropathy","volume":"10","author":"Rizk","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2023.04.029_bib10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1681\/ASN.2010050451","article-title":"The development of atypical hemolytic uremic syndrome depends on complement C5","volume":"22","author":"de Jorge","year":"2011","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib11","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2215\/CJN.06440616","article-title":"Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation","volume":"12","author":"Fakhouri","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib12","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1016\/S2352-3026(21)00028-4","article-title":"Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial","volume":"8","author":"Risitano","year":"2021","journal-title":"Lancet Haematol"},{"key":"10.1016\/j.ekir.2023.04.029_bib13","doi-asserted-by":"crossref","first-page":"7926","DOI":"10.1073\/pnas.1820892116","article-title":"Small-molecule factor B inhibitor for the treatment of complement-mediated diseases","volume":"116","author":"Schubart","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ekir.2023.04.029_bib14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system Part I - Molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2023.04.029_bib15","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.semnephrol.2013.08.003","article-title":"Atypical hemolytic uremic syndrome","volume":"33","author":"Kavanagh","year":"2013","journal-title":"Semin Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00467-015-3076-8","article-title":"An international consensus approach to the management of atypical hemolytic uremic syndrome in children","volume":"31","author":"Loirat","year":"2016","journal-title":"Pediatr Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib17","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1182\/blood.2020009280","article-title":"Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study","volume":"137","author":"Fakhouri","year":"2021","journal-title":"Blood"},{"key":"10.1016\/j.ekir.2023.04.029_bib18","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.3389\/fimmu.2019.02166","article-title":"Complement inhibitors in clinical trials for glomerular diseases","volume":"10","author":"Zipfel","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2023.04.029_bib19","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.ekir.2020.05.003","article-title":"Functional assessment of fatigue and other patient-reported outcomes in patients enrolled in the global aHUS registry","volume":"5","author":"Greenbaum","year":"2020","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.ekir.2023.04.029_bib20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2147\/IJNRD.S215370","article-title":"Optimal management of atypical hemolytic uremic disease: challenges and solutions","volume":"12","author":"Raina","year":"2019","journal-title":"Int J Nephrol Renovasc Dis"},{"key":"10.1016\/j.ekir.2023.04.029_bib21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/1744-9987.12763","article-title":"Atypical hemolytic-uremic syndrome: an update on pathophysiology, diagnosis, and treatment","volume":"23","author":"Raina","year":"2019","journal-title":"Ther Apher Dial"},{"key":"10.1016\/j.ekir.2023.04.029_bib23","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s00467-018-4091-3","article-title":"Eculizumab in atypical hemolytic uremic syndrome: strategies toward restrictive use","volume":"34","author":"Wijnsma","year":"2019","journal-title":"Pediatr Nephrol"},{"key":"10.1016\/j.ekir.2023.04.029_bib24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/ng.2590","article-title":"Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome","volume":"45","author":"Lemaire","year":"2013","journal-title":"Nat Genet"},{"key":"10.1016\/j.ekir.2023.04.029_bib25","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.kint.2020.01.045","article-title":"Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy","volume":"97","author":"Brocklebank","year":"2020","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2023.04.029_bib26","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.ekir.2021.03.884","article-title":"Long-term efficacy and safety of the long-acting complement C5 inhibitor ravulizumab for the treatment of atypical hemolytic uremic syndrome in adults","volume":"6","author":"Barbour","year":"2021","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.ekir.2023.04.029_bib27","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.kint.2020.01.035","article-title":"The long-acting C5 inhibitor, ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome na\u00efve to complement inhibitor treatment","volume":"97","author":"Rondeau","year":"2020","journal-title":"Kidney Int"},{"issue":"suppl 1","key":"10.1016\/j.ekir.2023.04.029_bib28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/ijlh.13954","article-title":"Diagnosis and treatment of thrombotic microangiopathy","volume":"44","author":"Thompson","year":"2022","journal-title":"Int J Lab Hematol"},{"issue":"suppl 3","key":"10.1016\/j.ekir.2023.04.029_bib29","article-title":"MO042LNP023: a novel oral complement alternative pathway factor B inhibitor for the treatment of glomerular disease","volume":"35","author":"Webb","year":"2020","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.ekir.2023.04.029_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.747594","article-title":"Alternative complement pathway inhibition does not abrogate meningococcal killing by serum of vaccinated individuals","volume":"12","author":"Ispasanie","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2023.04.029_bib31","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/j.ekir.2022.05.017","article-title":"Randomized Phase II Janus study of atacicept in patients with IgA nephropathy and persistent proteinuria","volume":"7","author":"Barratt","year":"2022","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.ekir.2023.04.029_bib32","doi-asserted-by":"crossref","DOI":"10.1681\/ASN.20213210S1B8b","article-title":"Iptacopan, a novel oral complement factor B (FB) inhibitor, significantly reduces proteinuria and C3 deposit scores in native and transplanted kidneys C3 glomerulopathy (C3G) patients","volume":"32","author":"Wong","year":"2021","journal-title":"J Am Soc Nephrol"},{"issue":"suppl 1","key":"10.1016\/j.ekir.2023.04.029_bib33","article-title":"LNP023: a novel oral complement alternative pathway factor B inhibitor safely and effectively stabilises EGFR in C3 glomerulopathy","volume":"36","author":"Wong","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.ekir.2023.04.029_bib34","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/ajt.12077","article-title":"Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome","volume":"13","author":"Le Quintrec","year":"2013","journal-title":"Am J Transplant"},{"key":"10.1016\/j.ekir.2023.04.029_bib35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1055\/s-0030-1262887","article-title":"Transplantation in atypical hemolytic uremic syndrome","volume":"36","author":"Kavanagh","year":"2010","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.ekir.2023.04.029_bib36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1053\/j.ajkd.2015.12.034","article-title":"Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial","volume":"68","author":"Fakhouri","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.ekir.2023.04.029_bib37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.kint.2020.10.046","article-title":"The long-acting C5 inhibitor, ravulizumab, is effective and safe in pediatric patients with atypical hemolytic uremic syndrome na\u00efve to complement inhibitor treatment","volume":"100","author":"Ariceta","year":"2021","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2023.04.029_bib38","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.kint.2020.03.011","article-title":"Is ravulizumab the new treatment of choice for atypical hemolytic uremic syndrome (aHUS)?","volume":"97","author":"Menne","year":"2020","journal-title":"Kidney Int"},{"key":"10.1016\/j.ekir.2023.04.029_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.732146","article-title":"Alternative complement pathway inhibition abrogates pneumococcal opsonophagocytosis in vaccine-na\u00efve, but not in vaccinated individuals","volume":"12","author":"Muri","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.ekir.2023.04.029_bib40","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1056\/NEJMoa1208981","article-title":"Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome","volume":"368","author":"Legendre","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ekir.2023.04.029_bib41","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1182\/blood-2005-02-0564","article-title":"Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria","volume":"106","author":"Hill","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.ekir.2023.04.029_bib42","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2018-09-876136","article-title":"Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study","volume":"133","author":"Lee","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.ekir.2023.04.029_bib43","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s40265-021-01481-6","article-title":"Ravulizumab: a review in atypical haemolytic uraemic syndrome","volume":"81","author":"Syed","year":"2021","journal-title":"Drugs"},{"key":"10.1016\/j.ekir.2023.04.029_bib44","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.ekir.2021.04.036","article-title":"Ravulizumab for the treatment of aHUS in adults: improving quality of life","volume":"6","author":"Legendre","year":"2021","journal-title":"Kidney Int Rep"}],"container-title":["Kidney International Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024923012937?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468024923012937?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T03:44:21Z","timestamp":1762832661000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468024923012937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["S2468024923012937"],"URL":"https:\/\/doi.org\/10.1016\/j.ekir.2023.04.029","relation":{},"ISSN":["2468-0249"],"issn-type":[{"value":"2468-0249","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design and Rationale of the APPELHUS Phase 3 Open-Label Study of Factor B Inhibitor Iptacopan for Atypical Hemolytic Uremic Syndrome","name":"articletitle","label":"Article Title"},{"value":"Kidney International Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ekir.2023.04.029","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 International Society of Nephrology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}