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Although C5 inhibitors, such as eculizumab and ravulizumab, have markedly improved outcomes, renal recovery remains limited in cases complicated by hypertensive emergency (HE) or malignant hypertension, likely due to complement-independent vascular injury. Angiotensin receptor\u2013neprilysin inhibitor therapy exerts dual actions of renin\u2013angiotensin system blockade and augmentation of natriuretic peptide signaling. Additionally, this therapy has recently demonstrated renal benefits in thrombotic microangiopathy with HE compared with conventional renin\u2013angiotensin system inhibitors. However, the combined use of an angiotensin receptor\u2013neprilysin inhibitor with a C5 inhibitor in aHUS with HE has not been reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 57-year-old Japanese man presented with marked anemia, severe renal dysfunction (serum creatinine concentration: 10.19\u2009mg\/dL; eGFR 5\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ), and hypertensive emergency (blood pressure: 198\/102\u2009mmHg). Laboratory examinations showed hemolytic anemia and thrombocytopenia, leading to a diagnosis of thrombotic microangiopathy. Plasma exchange was performed, and intravenous antihypertensive therapy was initiated on day 1. Ravulizumab was started on day 2 after thrombotic thrombocytopenic purpura and Shiga toxin-associated HUS were excluded, and aHUS was clinically suspected on the basis of isolated C3 hypocomplementemia. Despite the requirement for initial hemodialysis, renal function gradually improved, allowing withdrawal of dialysis by day 14. A renal biopsy showed thrombotic microangiopathy with intravascular thrombi and concentric arteriolar wall thickening resembling onion-skin lesions. Consequently, sacubitril\/valsartan was initiated on day 23, resulting in further renal recovery (creatinine concentration: 3.79\u2009mg\/dL on day 22 to 1.23\u2009mg\/dL at 1\u2009year; eGFR 14 to 48\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      at 1\u2009year) accompanied by improved blood pressure control. Genetic testing identified a heterozygous C3 c.493G\u2009&gt;\u2009T (p.Val165Phe) variant, which confirmed C3 mutation-associated aHUS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We report the first case of C3 mutation-associated aHUS with HE, which was successfully treated with a combination of ravulizumab and sacubitril\/valsartan. The renal improvement in this patient may suggest a potential, but unproven, contribution of angiotensin receptor\u2013neprilysin inhibitor-based renin\u2013angiotensin modulation to kidney recovery when added to complement inhibition in aHUS complicated by HE, although its independent effect remains unclear. Further cohort studies are warranted to clarify its potential therapeutic synergy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12882-026-04797-1","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:04:48Z","timestamp":1770887088000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["C3 mutation-associated atypical hemolytic uremic syndrome with severe renal dysfunction and hypertensive emergency successfully treated with ravulizumab and sacubitril\/valsartan: a case report"],"prefix":"10.1186","volume":"27","author":[{"given":"Hiroki","family":"Yanagidani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Maeoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Kumano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Okubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritoshi","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Masaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"4797_CR1","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1681\/ASN.2004100861","volume":"16","author":"M Noris","year":"2005","unstructured":"Noris M, Remuzzi G. 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