{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:37:57Z","timestamp":1792708677088,"version":"4.5.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"abstract":"\n Background:<\/jats:title>\n Complement activation in IgA nephropathy (IgAN) drives inflammation, nephron loss, and progressive kidney damage. We evaluated urinary biomarkers among participants with IgAN treated with ravulizumab (terminal complement C5 inhibitor) versus placebo in the Phase 2 SANCTUARY trial and healthy donors.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n This exploratory analysis evaluated data from 60 participants with IgAN from SANCTUARY (NCT04564339) and 25 healthy donors. Spot urine samples were collected pre-dose on days 1, 15, 71, 127, and 183, and thereafter Q8W. Urinary biomarkers of complement activation (soluble C5b-9 [sC5b-9] and factor Ba), renal inflammation (CD163), and tubular injury (KIM-1, NGAL) were assessed, normalized to creatinine. Biomarkers were compared between subgroups: baseline 24-hour urine protein (1-2 vs >2 g\/day) and eGFR (30-60 vs \u226560-90 vs \u226590 mL\/min\/1.73 m\n 2<\/jats:sup>\n ). Ravulizumab and placebo groups were compared using mixed model for repeated measures (MMRM).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Baseline levels of sC5b-9\/Cr, Ba\/Cr, CD163\/Cr, and KIM-1\/Cr were significantly elevated in participants with IgAN versus healthy donors (\n P<\/jats:italic>\n < 0.001 for all); 93% participants had elevated sC5b-9\/Cr. Baseline sC5b-9\/Cr, CD163\/Cr, and KIM-1\/Cr were significantly higher in participants with baseline urine protein >2 g\/day versus 1-2 g\/day (\n P<\/jats:italic>\n < 0.05 for all). Baseline sC5b-9\/Cr and Ba\/Cr were highest in participants with eGFR 30-60 mL\/min\/1.73 m\n 2<\/jats:sup>\n (\n P<\/jats:italic>\n < 0.05 across subgroups). Significantly greater reductions in sC5b-9\/Cr and Ba\/Cr were observed with ravulizumab versus placebo at Weeks 2, 10, 18, and 26; in CD163\/Cr and KIM-1\/Cr at Weeks 10, 18, and 26 (MMRM;\n P<\/jats:italic>\n < 0.05 for all). Reductions in these biomarkers were sustained through Week 50 and were observed after crossover from placebo to ravulizumab at Week 26.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Ravulizumab led to early, sustained, and significant reductions in urinary biomarkers of complement activation and decreases in markers of renal inflammation and proximal tubular injury; this is consistent with its observed effect on proteinuria.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000001243","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:00:11Z","timestamp":1792706411000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Biomarker Analysis of the SANCTUARY Trial"],"prefix":"10.2215","author":[{"given":"Tobin J.","family":"Cammett","sequence":"first","affiliation":[{"name":"Translational Biomarker Research, Alexion, AstraZeneca Rare Disease, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6536-1985","authenticated-orcid":false,"given":"Ellen E.","family":"Millman","sequence":"additional","affiliation":[{"name":"Translational Biomarker Research, Alexion, AstraZeneca Rare Disease, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1805-7506","authenticated-orcid":false,"given":"Julio","family":"Luna","sequence":"additional","affiliation":[{"name":"Translational Biomarker Research, Alexion, AstraZeneca Rare Disease, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3289-3476","authenticated-orcid":false,"given":"Kara","family":"Rice","sequence":"additional","affiliation":[{"name":"Biostatistics, Alexion, AstraZeneca Rare Disease, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Nolan","sequence":"additional","affiliation":[{"name":"Clinical Development, Alexion, AstraZeneca Rare Disease, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-1851","authenticated-orcid":false,"given":"Youssef M.K.","family":"Farag","sequence":"additional","affiliation":[{"name":"Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-7934","authenticated-orcid":false,"given":"Richard","family":"Lafayette","sequence":"additional","affiliation":[{"name":"Stanford Glomerular Disease Center, Stanford University Medical Center, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-7229","authenticated-orcid":false,"given":"Jonathan","family":"Barratt","sequence":"additional","affiliation":[{"name":"University of Leicester, Leicester, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.0000001243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:00:11Z","timestamp":1792706411000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.0000001243"}},"subtitle":["Insights into IgA Nephropathy Pathophysiology and Ravulizumab Mechanism of Action"],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2215\/cjn.0000001243","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2026-04-27","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-02","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}