{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:43:43Z","timestamp":1793133823995,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Alexion, AstraZeneca Rare Disease, Boston, MA"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nephrol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This\u00a0analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200971) and without (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      While demographics were similar, patients with aHUS\u2009+\u2009malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants\/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants\/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS\u2009+\u2009malignant hypertension (adjusted HR (95% CI), 0.11 [0.01\u20130.87],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.036).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS\u2009\u00b1\u2009malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration details<\/jats:title>\n                    <jats:p>Atypical Hemolytic-Uremic Syndrome (aHUS) Registry.<\/jats:p>\n                    <jats:p>Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s40620-022-01465-z","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T05:02:32Z","timestamp":1663995752000},"page":"817-828","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Clinical characteristics and outcomes of a patient population with atypical hemolytic uremic syndrome and malignant hypertension: analysis from the Global aHUS registry"],"prefix":"10.1093","volume":"36","clinical-trial-number":[{"clinical-trial-number":"nct01522183","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jean-Michel","family":"Halimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Al-Dakkak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Anokhina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Ardissino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Licht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai H.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Massart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan Vande","family":"Walle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rondeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"1465_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0140-6736(17)30062-4","volume":"390","author":"F Fakhouri","year":"2017","unstructured":"Fakhouri F, Zuber J, Fr\u00e9meaux-Bacchi V, Loirat C (2017) Haemolytic uraemic syndrome. 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Imad Al-Dakkak is an employee and stockholder of Alexion, AstraZeneca Rare Disease. Katerina Anokhina is an employee and stockholder of Alexion, AstraZeneca Rare Disease. Gianluigi Ardissino has received honoraria from Alexion, AstraZeneca Rare Disease; Alnylam; Roche; Novartis; and Eligo Bioscience. Christoph Licht has received honoraria from Alexion, AstraZeneca Rare Disease; Apellis; Genentech \u2013 Hoffman La Roche; Novartis; unrestricted research grants from Alexion, Aurin Biotech, Fresenius and Pfizer; and was Chair of the Global aHUS Registry (2013\u20132020). Wai Lim has received speaker fees and\/or education grants from Alexion, AstraZeneca Rare Disease; Novartis; and Astellas. Annick Massart has received honoraria from Alexion, AstraZeneca Rare Disease and Amicus Therapeutics. Franz Schaefer has received honoraria from Alexion, AstraZeneca Rare Disease; Alnylam; Astellas; AstraZeneca; Bayer; Otsuka; Roche; and is Chair of the Global aHUS Registry. Johan Vande Walle has received honoraria from Alexion, AstraZeneca Rare Disease; Alnylam; Astellas; Bayer; Chies; Ferring; Kyowa Kyrin; Otsuka; is a member of the Global aHUS Registry; and is chair of the National aHUS Registry. Eric Rondeau has received honoraria, fees and grants from Alexion, AstraZeneca Rare Disease.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This was a multicenter study comprising many different sites of enrollment. Federal, provincial, and local regulations and International Conference on Harmonization guidelines, if relevant, required that approval was obtained from an Ethics Committee (EC)\/IRB prior to participation of patients in research studies. Where required and prior to the study onset, the EC\/IRB must have approved the protocol, informed consent, advertisements to be used for patient recruitment, and any other written information regarding this study to be provided to the patient or the patient\u2019s parents\/legal guardian. The sites maintained and made available for review by the sponsor or its designee documentation of all EC\/IRB approvals and of the EC\/IRB compliance with International Conference on Harmonization Guidance E6: Good Clinical Practice, if relevant. All EC\/IRB approvals were signed by the EC\/IRB chairman or designee and identified the EC\/IRB name and address, the clinical protocol by title and\/or protocol number, and the date approval and\/or favorable opinion was granted. The investigator conducted all aspects of this study in accordance with all national, provincial, and local laws of the pertinent regulatory authorities.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}},{"value":"A written informed consent was obtained from each patient prior to participation in the study. The sponsor or its designee could provide an informed consent template to the sites, if required. If the site made any The sponsor or its designee could provide an informed consent template to the sites, if required. If the site made any institution-specific modifications, the sponsor or its designee could review the consent prior to IRB\/EC submission. The investigator or the sponsor would then submit the approved, revised consent to the appropriate IRB\/EC for review and approval prior to the start of the study. If the consent form was revised during the course of the study, all active participating patients to whom the revision may have had an impact must have signed the revised form. Before recruitment and enrollment, each patient was given a full explanation of the study and was allowed time to read the approved informed consent form. Once the investigator was assured that the individual understood the implications of participating in the study, the patient was asked to give consent to participate in the study by signing the informed consent form. The investigator provided a copy of the signed informed consent to the patient. The original form was maintained in the study files at the site.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}