{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:45:20Z","timestamp":1791251120956,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Improvement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody\u2013associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin\u2013angiotensin\u2013aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) &amp;gt;1 g\/g creatinine and an estimated glomerular filtration rate (eGFR) &amp;gt;60 mL\/min\/1.73 m2 or &amp;gt;45 mL\/min\/1.73 m2 if eGFR has not declined &amp;gt;10 mL\/min\/1.73 m2 over the previous 24 weeks. If the UPCR remained at &amp;gt;1 g\/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR &amp;gt;1 g\/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of \u223c50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This short-term pilot study showed an improvement in the slope of the UPCR, with \u223c50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfab294","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T20:10:53Z","timestamp":1640376653000},"page":"922-928","source":"Crossref","is-referenced-by-count":91,"title":["C5a receptor inhibitor avacopan in immunoglobulin A nephropathy\u2014an open-label pilot study"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-9941","authenticated-orcid":false,"given":"Annette","family":"Bruchfeld","sequence":"first","affiliation":[{"name":"Department of Health, Medicine and Caring Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden"},{"name":"Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Magin","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Nachman","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Minneapolis, University of Minnesota, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Parikh","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lafayette","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Stanford University, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Potarca","sequence":"additional","affiliation":[{"name":"ChemoCentryx, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichang","family":"Miao","sequence":"additional","affiliation":[{"name":"ChemoCentryx, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirow","family":"Bekker","sequence":"additional","affiliation":[{"name":"ChemoCentryx, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"2022042902154336500_bib1","first-page":"694","article-title":"Intercapillary deposits of IgA-IgG","volume":"74","author":"Berger","year":"1968","journal-title":"J Urol Nephrol (Paris)"},{"key":"2022042902154336500_bib2","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1523-1755.2004.00837.x","article-title":"Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies","volume":"66","author":"Li","year":"2004","journal-title":"Kidney Int"},{"key":"2022042902154336500_bib3","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1056\/NEJMra1206793","article-title":"IgA nephropathy","volume":"368","author":"Wyatt","year":"2013","journal-title":"N Engl J Med"},{"key":"2022042902154336500_bib4","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1681\/ASN.2011050464","article-title":"The pathophysiology of IgA nephropathy","volume":"22","author":"Hitoshi","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"2022042902154336500_bib5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/ki.2015.322","article-title":"The MEST score provides earlier risk prediction in IgA nephropathy","volume":"89","author":"Barbour","year":"2016","journal-title":"Kidney Int"},{"key":"2022042902154336500_bib6","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1093\/ndt\/gfy302","article-title":"Is there long-term value of pathology scoring in immunoglobulin A nephropathy? 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