{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:28:14Z","timestamp":1791563294598,"version":"4.3.4"},"reference-count":32,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016198","name":"Idorsia Pharmaceuticals Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Research and Innovation Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R001359\/1"],"award-info":[{"award-number":["MR\/R001359\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004185","name":"Northern Counties Kidney Research Fund","doi-asserted-by":"publisher","award":["KJM\/HD\/IYP\/GT\/CC"],"award-info":[{"award-number":["KJM\/HD\/IYP\/GT\/CC"]}],"id":[{"id":"10.13039\/501100004185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017555","name":"Catalyst Biosciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["kidney-international.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.kint.2024.12.016","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T19:49:03Z","timestamp":1737488943000},"page":"700-713","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["The membrane attack complex drives thrombotic microangiopathy in complement mediated atypical hemolytic uremic syndrome"],"prefix":"10.1016","volume":"107","author":[{"given":"Kate","family":"Smith-Jackson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioleta M.","family":"Zelek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hoyler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne M.","family":"Martinic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth G.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Connelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel Y.","family":"Pappworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-0072","authenticated-orcid":false,"given":"David","family":"Kavanagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1312-5411","authenticated-orcid":false,"given":"Kevin J.","family":"Marchbank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.kint.2024.12.016_bib1","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.kint.2024.12.016_bib2","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 naive to complement inhibitor treatment","volume":"97","author":"Rondeau","year":"2020","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2024.12.016_bib3","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1097\/TP.0000000000004355","article-title":"Assessing the impact of prophylactic eculizumab on renal graft survival in atypical hemolytic uremic syndrome","volume":"107","author":"Glover","year":"2023","journal-title":"Transplantation"},{"key":"10.1016\/j.kint.2024.12.016_bib4","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1182\/blood.2022018833","article-title":"Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study","volume":"142","author":"Brocklebank","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.kint.2024.12.016_bib5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.kint.2019.01.009","article-title":"Differential contribution of C5aR and C5b-9 pathways to renal thrombic microangiopathy and macrovascular thrombosis in mice carrying an atypical hemolytic syndrome-related factor H mutation","volume":"96","author":"Ueda","year":"2019","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2024.12.016_bib6","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1182\/blood-2009-01-199117","article-title":"Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodies","volume":"114","author":"Seshan","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.kint.2024.12.016_bib7","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1172\/JCI99296","article-title":"Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice","volume":"129","author":"Smith-Jackson","year":"2019","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.kint.2024.12.016_bib8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/383086a0","article-title":"The C5a chemoattractant receptor mediates mucosal defence to infection","volume":"383","author":"Hopken","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.kint.2024.12.016_bib9","article-title":"Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol"},{"key":"10.1016\/j.kint.2024.12.016_bib10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/bcpt.13756","article-title":"First-in-human study with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5aR1) antagonist, supported by pharmacokinetic predictions from animals to patients","volume":"131","author":"Ort","year":"2022","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1016\/j.kint.2024.12.016_bib11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1600-6143.2008.02451.x","article-title":"The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection","volume":"9","author":"Locke","year":"2009","journal-title":"Am J Transplant"},{"key":"10.1016\/j.kint.2024.12.016_bib12","first-page":"2286","article-title":"Eculizumab as rescue therapy in severe resistant lupus nephritis","volume":"54","author":"Pickering","year":"2015","journal-title":"Rheumatology"},{"key":"10.1016\/j.kint.2024.12.016_bib13","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.612402","article-title":"Monoclonal antibodies capable of inhibiting complement downstream of C5 in multiple species","volume":"11","author":"Zelek","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2024.12.016_bib14","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1053\/j.ajkd.2022.10.014","article-title":"Renal thrombotic microangiopathy: a review","volume":"81","author":"Genest","year":"2023","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.kint.2024.12.016_bib15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000445171","article-title":"Non-transgenic mouse models of kidney disease","volume":"133","author":"Rabe","year":"2016","journal-title":"Nephron"},{"key":"10.1016\/j.kint.2024.12.016_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.imbio.2023.152707","article-title":"Complement and coagulation crosstalk\u2014factor H in the spotlight","volume":"228","author":"Heurich","year":"2023","journal-title":"Immunobiology"},{"key":"10.1016\/j.kint.2024.12.016_bib17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3390\/biom2010046","article-title":"Factor H: a complement regulator in health and disease, and a mediator of cellular interactions","volume":"2","author":"Kopp","year":"2012","journal-title":"Biomolecules"},{"key":"10.1016\/j.kint.2024.12.016_bib18","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1074\/jbc.M609178200","article-title":"The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding","volume":"282","author":"Scola","year":"2007","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.kint.2024.12.016_bib19","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.3389\/fimmu.2020.01875","article-title":"The complement C3a and C3a receptor pathway in kidney diseases","volume":"11","author":"Gao","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2024.12.016_bib20","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1046\/j.1523-1755.2001.0600031018.x","article-title":"Intravenous immunoglobulin protects against experimental thrombotic microangiopathy","volume":"60","author":"Jefferson","year":"2001","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2024.12.016_bib21","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1182\/blood.2020007206","article-title":"Complement and the prothrombotic state","volume":"139","author":"Schmidt","year":"2022","journal-title":"Blood"},{"key":"10.1016\/j.kint.2024.12.016_bib22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.kint.2019.02.038","article-title":"Terminal complement effectors in atypical hemolytic uremic syndrome: C5a, C5b-9, or a bit of both?","volume":"96","author":"Noris","year":"2019","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2024.12.016_bib23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/imr.13150","article-title":"The complement alternative pathway and hemostasis","volume":"313","author":"Noris","year":"2023","journal-title":"Immunol Rev"},{"key":"10.1016\/j.kint.2024.12.016_bib24","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.molimm.2011.04.014","article-title":"Inhibiting the C5-C5a receptor axis","volume":"48","author":"Woodruff","year":"2011","journal-title":"Mol Immunol"},{"key":"10.1016\/j.kint.2024.12.016_bib25","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1055\/s-0038-1655974","article-title":"C5a induces tissue factor activity on endothelial cells","volume":"77","author":"Ikeda","year":"1997","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.kint.2024.12.016_bib26","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1016\/S0021-9258(19)39666-8","article-title":"Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex","volume":"265","author":"Hamilton","year":"1990","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.kint.2024.12.016_bib27","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1084\/jem.158.2.603","article-title":"Human platelet activation by C3a and C3a des-arg","volume":"158","author":"Polley","year":"1983","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.kint.2024.12.016_bib28","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1084\/jem.147.6.1713","article-title":"The human complement system in thrombin-mediated platelet function","volume":"147","author":"Polley","year":"1978","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.kint.2024.12.016_bib29","doi-asserted-by":"crossref","first-page":"9053","DOI":"10.1016\/S0021-9258(18)81901-9","article-title":"Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface","volume":"264","author":"Hattori","year":"1989","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.kint.2024.12.016_bib30","doi-asserted-by":"crossref","first-page":"6457","DOI":"10.4049\/jimmunol.1300610","article-title":"Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O)","volume":"190","author":"Saggu","year":"2013","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.kint.2024.12.016_bib31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1046\/j.1365-2249.2000.01263.x","article-title":"Modulation of complement membrane attack by local C7 synthesis","volume":"121","author":"Wurzner","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.kint.2024.12.016_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.968206","article-title":"Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients","volume":"13","author":"Lekova","year":"2022","journal-title":"Front Immunol"}],"container-title":["Kidney International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253825000602?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253825000602?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:57:27Z","timestamp":1763668647000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253825000602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["S0085253825000602"],"URL":"https:\/\/doi.org\/10.1016\/j.kint.2024.12.016","relation":{},"ISSN":["0085-2538"],"issn-type":[{"value":"0085-2538","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The membrane attack complex drives thrombotic microangiopathy in complement mediated atypical hemolytic uremic syndrome","name":"articletitle","label":"Article Title"},{"value":"Kidney International","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.kint.2024.12.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 International Society of Nephrology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}