{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T21:02:35Z","timestamp":1770152555430,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis are a group of autoimmune diseases characterized by inflammation of the microvasculature, leading to life-threatening complications, including kidney disease. These diseases are associated with a high morbidity and mortality rate. Conventional treatment modalities have evolved towards personalized therapies intending to mitigate inflammation and minimize the adverse effects of traditional immunosuppressive agents. Avacopan, a novel C5a receptor inhibitor, represents a promising therapeutic option for vasculitis with renal involvement. This article provides a comprehensive review of the role of complement in the pathogenesis of vasculitis with renal involvement and the role of avacopan for its treatment, taking into account recent updates to both the EULAR and KDIGO guidelines and published experience of avacopan use in real clinical settings.<\/jats:p>","DOI":"10.3390\/jcm13226676","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T07:47:16Z","timestamp":1730965636000},"page":"6676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of Avacopan on Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-9615","authenticated-orcid":false,"given":"Justo","family":"Sandino","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hospital 12 de Octubre, 28041 Madrid, Spain"},{"name":"Research Institute of University Hospital 12 de Octubre (imas12), Department of Medicine, Complutense University of Madrid, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-6973","authenticated-orcid":false,"given":"Enrique","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital 12 de Octubre, 28041 Madrid, Spain"},{"name":"Research Institute of University Hospital 12 de Octubre (imas12), Department of Medicine, Complutense University of Madrid, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","first-page":"284","article-title":"Systemic vasculitis in the 1980s\u2014Is there an increasing incidence of Wegener\u2019s granulomatosis and microscopic polyarteritis?","volume":"24","author":"Andrews","year":"1990","journal-title":"J. R. Coll. Physicians Lond."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41584-021-00718-8","article-title":"Global epidemiology of vasculitis","volume":"18","author":"Watts","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41584-018-0145-y","article-title":"Pathogenesis and therapeutic interventions for ANCA-associated vasculitis","volume":"15","author":"Nakazawa","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2215\/CJN.05610611","article-title":"Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease","volume":"7","author":"McGregor","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1136\/ard-2022-223764","article-title":"EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update","volume":"83","author":"Hellmich","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1681\/ASN.2016111179","article-title":"Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis","volume":"28","author":"Jayne","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/acr2.11185","article-title":"Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitis","volume":"2","author":"Merkel","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2353\/ajpath.2007.060573","article-title":"Alternative Complement Pathway in the Pathogenesis of Disease Mediated by Anti-Neutrophil Cytoplasmic Autoantibodies","volume":"170","author":"Xiao","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.2215\/CJN.06230614","article-title":"Molecules Great and Small","volume":"10","author":"Mathern","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.4049\/jimmunol.1500793","article-title":"Annexin A2 Enhances Complement Activation by Inhibiting Factor H","volume":"196","author":"Renner","year":"2016","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype","volume":"5","author":"Noris","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1046\/j.1365-2249.1996.d01-776.x","article-title":"CR1 stump peptide and terminal complement complexes are found in the glomeruli of lupus nephritis patients","volume":"105","author":"Teixeira","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/ki.1994.247","article-title":"Localization of the complement regulatory proteins in the normal human kidney","volume":"46","author":"Ichida","year":"1994","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S186","DOI":"10.1097\/01.ASN.0000070032.58017.20","article-title":"Chronic Progression of Tubulointerstitial Damage in Proteinuric Renal Disease Is Mediated by Complement Activation","volume":"14","author":"Hsu","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1096\/fj.07-8719com","article-title":"Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury","volume":"22","author":"Sheerm","year":"2008","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1096\/fj.05-4747com","article-title":"Local extravascular pool of C3 is a determinant of postischemic acute renal failure","volume":"20","author":"Farrar","year":"2006","journal-title":"FASEB J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1007\/s10067-016-3384-9","article-title":"Circulating C3 levels predict renal and global outcome in patients with renal vasculitis","volume":"35","author":"Villacorta","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ki.2012.313","article-title":"Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis","volume":"83","author":"Gou","year":"2013","journal-title":"Kidney Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1111\/j.1523-1755.2004.00632.x","article-title":"Immune complex deposits in ANCA-associated crescentic glomerulonephritis: A study of 126 cases","volume":"65","author":"Haas","year":"2004","journal-title":"Kidney Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s10875-008-9268-2","article-title":"Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis","volume":"29","author":"Xing","year":"2009","journal-title":"J. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/BOR.0000000000000914","article-title":"The complement system in antineutrophil cytoplasmic antibody-associated vasculitis: Pathogenic player and therapeutic target","volume":"35","author":"Mazzariol","year":"2023","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"750","DOI":"10.2215\/CJN.07910814","article-title":"Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis","volume":"10","author":"Chen","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.kint.2023.10.013","article-title":"Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis","volume":"105","author":"Acevedo","year":"2024","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1681\/ASN.2013020143","article-title":"C5a receptor (CD88) blockade protects against MPO-ANCA GN","volume":"25","author":"Xiao","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1056\/NEJMoa2023386","article-title":"Avacopan for the Treatment of ANCA-Associated Vasculitis","volume":"384","author":"Jayne","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/ndt\/gfad237","article-title":"ANCA-associated vasculitis-treatment standard","volume":"39","author":"Chalkia","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.ekir.2024.03.022","article-title":"Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis","volume":"9","author":"Zonozi","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/mrcr\/rxad019","article-title":"Gradual increase of avacopan dose with concomitant ursodeoxycholic acid use may help avoid the risk of C5a receptor inhibitor-induced liver injury in antineutrophil cytoplasmic antibody-associated vasculitis","volume":"7","author":"Kataoka","year":"2023","journal-title":"Mod. Rheumatol. Case Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/1756-185X.14645","article-title":"Thrombocytopenia during avacopan administration: A case report","volume":"26","author":"Morimoto","year":"2023","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ekir.2024.01.006","article-title":"Use of Avacopan in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Estimated Glomerular Filtration Rate <15 mL\/min per 1.73 m2","volume":"9","author":"Barr","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/ndt\/gfae018","article-title":"Long-term outcome of kidney function in patients with ANCA-associated vasculitis","volume":"39","author":"Moi","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.ekir.2023.01.039","article-title":"Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan","volume":"8","author":"Cortazar","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1016\/j.ekir.2024.07.007","article-title":"Avacopan in Anti-Neutrophil Cytoplasmic Autoantibodies\u2013Associated Vasculitis in a Real-World Setting","volume":"9","author":"Zimmermann","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Draibe, J., Espigol-Frigol\u00e9, G., Cid, M.C., Prados, M.C., Guill\u00e9n, E., Villacorta, J., Vega, C., Martins, J., daSilva, I., and Martin-Gomez, M.A. (Rheumatology, 2024). The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain, Rheumatology, ahead of print.","DOI":"10.1093\/rheumatology\/keae534"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e451","DOI":"10.1016\/S2665-9913(23)00092-9","article-title":"The impact of treatment with avacopan on health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis: A post-hoc analysis of data from the ADVOCATE trial","volume":"5","author":"Strand","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.kint.2023.10.009","article-title":"Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA\u2013Associated Vasculitis","volume":"105","author":"Floege","year":"2024","journal-title":"Kidney Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1136\/ard-2023-224816","article-title":"Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial","volume":"83","author":"Geetha","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/acr2.11726","article-title":"Treatment of Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitis With Diffuse Alveolar Hemorrhage With Avacopan","volume":"6","author":"Falde","year":"2024","journal-title":"ACR Open Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/ndt\/gfae020","article-title":"Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage","volume":"39","author":"Chalkia","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ekir.2022.10.033","article-title":"Tailored Use of Avacopan in a Case With Refractory Antineutrophil Cytoplasmic Antibody-Associated Renal Vasculitis and Concominant Complement System Activation","volume":"8","author":"Hakroush","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e413","DOI":"10.1016\/S2665-9913(23)00131-5","article-title":"The Glucocorticoid Toxicity Index-Metabolic Domains, an abridged version of the Glucocorticoid Toxicity Index: Post-hoc analysis of data from the ADVOCATE trial","volume":"5","author":"Patel","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1136\/annrheumdis-2013-203249","article-title":"EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases","volume":"72","author":"Duru","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ekir.2021.11.036","article-title":"Compassionate Use of Avacopan in Difficult-to-Treat Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitis","volume":"7","author":"Bredewold","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/1744666X.2023.2162041","article-title":"Avacopan for the treatment of ANCA-associated vasculitis: An update","volume":"19","author":"Osman","year":"2023","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gabilan, C., Belliere, J., Moranne, O., Pfirmann, P., Samson, M., Delattre, V., Thoreau, B., Gueutin, V., Boyer, A., and Leurs, A. (Rheumatology, 2024). Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: A multicentre real-world study, Rheumatology, ahead of print.","DOI":"10.1093\/rheumatology\/keae359"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1056\/NEJMoa1803537","article-title":"Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis","volume":"382","author":"Walsh","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.2169\/internalmedicine.3072-23","article-title":"Improved Hearing Impairment of Granulomatosis with Polyangiitis Treated with Rituximab and Avacopan without Glucocorticoids","volume":"63","author":"Okubo","year":"2024","journal-title":"Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e306","DOI":"10.1093\/rheumatology\/kead173","article-title":"ANCA-MPO: Is this a useful test?","volume":"62","author":"Abrantes","year":"2023","journal-title":"Rheumatology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:27:44Z","timestamp":1760113664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/22\/6676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":48,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["jcm13226676"],"URL":"https:\/\/doi.org\/10.3390\/jcm13226676","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]}}}