{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:45:42Z","timestamp":1785843942517,"version":"3.56.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) are rare complement-mediated kidney diseases with differing injury sites and therapeutic targets. We conducted a time-limited rapid systematic review to synthesize clinical evidence on complement-targeted therapies. Rapid reviews streamline traditional systematic review methods to provide timely evidence for decision-making in situations where new regulatory approvals or clinical developments create an urgent need for synthesized evidence. The abbreviated timeframe was chosen to inform clinical practice following the March 2025 FDA approval of iptacopan and the July 2025 FDA approval of pegcetacoplan for C3G, at a time when clinicians required timely guidance on emerging therapeutic options. Seven databases were searched from inception to 24 April 2026, supplemented by Google Scholar,\n                    <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                    , and congress abstracts. Chinese databases were searched\n                    <jats:italic>post hoc<\/jats:italic>\n                    ; no additional eligible studies were identified. Risk of bias was assessed with RoB 2, ROBINS-I, or JBI checklist; certainty of evidence was summarized using GRADE. Narrative synthesis without meta-analysis was performed due to substantial heterogeneity. Thirty-eight studies were included (14 C3G, 22 aHUS, 2 both). In aHUS, uncontrolled observational evidence indicates that anti-C5 therapy is associated with haematologic remission in many patients, but causal inference is limited by lack of randomized or concurrent controlled data. The largest prospective single-arm study (Legendre et al.\n                    <jats:italic>n<\/jats:italic>\n                    = 37) reported 80% TMA-free status at 26 weeks. Real-world cohorts corroborated these findings, though estimates are subject to selection bias and confounding by indication. In C3G, eculizumab showed heterogeneous responses. The APPEAR-C3G trial (Kavanagh et al.\n                    <jats:italic>n<\/jats:italic>\n                    = 74) demonstrated that iptacopan achieved a 35.1% relative reduction in 24 h urine protein-to-creatinine ratio (UPCR) at 6 months vs. placebo (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0014). The VALIANT trial (Fakhouri et al.\n                    <jats:italic>n<\/jats:italic>\n                    = 124), now published in the New England Journal of Medicine, reported that pegcetacoplan reduced proteinuria by 68% at 26 weeks vs. placebo and achieved C3c clearance on biopsy in 71% of patients. Serious meningococcal infection remains a major safety concern. Based on low-certainty, non-randomized evidence, anti-C5 therapy in aHUS is associated with haematologic remission and renal recovery. In C3G, terminal complement blockade evidence remains weak, whereas factor B inhibition has emerging randomized evidence for short-term proteinuria reduction. Biomarker-guided patient selection and standardized outcomes should be priorities. This review employed narrative synthesis without meta-analysis; readers should not interpret reported percentages as pooled estimates.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>PROSPERO Registration<\/jats:title>\n                    <jats:p>CRD420261364711 (rapid registration, 9 April 2026).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1867718","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:10:26Z","timestamp":1785841826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement-targeted therapies for C3 glomerulopathy and atypical hemolytic uremic syndrome: a time-limited rapid systematic review with narrative synthesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Qishun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Wannan Medical University","place":["Wuhu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Wannan Medical University","place":["Wuhu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangli","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Wannan Medical University","place":["Wuhu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Wannan Medical University","place":["Wuhu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Wannan Medical University","place":["Wuhu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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 Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1016\/S0140-6736(25)01148-1","article-title":"Oral iptacopan therapy in patients with C3 glomerulopathy: a randomised, double-blind, parallel group, multicentre, placebo-controlled, phase 3 study","volume":"406","author":"Kavanagh","year":"2025","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1056\/NEJMoa2501510","article-title":"Trial of pegcetacoplan in C3 glomerulopathy and immune-complex 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