{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:04Z","timestamp":1786480324388,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n \n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 integrin was upregulated in kidney tubules and associated with fibrosis and reduced kidney function in human CKD.\n <\/jats:p>\n <\/jats:list-item>\n \n \n MEDI8367 blocked\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8-mediated TGF\u03b2 activation and reduced fibrosis in mouse unilateral ureteral obstruction model.\n <\/jats:p>\n <\/jats:list-item>\n \n \n In diabetic kidney disease mouse models,\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 inhibition improved kidney injury markers and preserved kidney function.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n CKD is a global health issue exacerbated by the rising prevalence of diabetes and obesity. Renal fibrosis, characterized by the accumulation of extracellular matrix proteins, is a critical factor in CKD progression. TGF-\n \u03b2<\/jats:italic>\n , a key profibrotic cytokine, plays a pivotal role in this process. However, systemic inhibition of TGF-\n \u03b2<\/jats:italic>\n has been limited by associated toxicities.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study explores the role of\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 integrin in renal fibrosis and its potential as a therapeutic target in CKD. We used various preclinical models of CKD, including humanized\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 mice and the db\/db uninephrectomy model, to investigate the role of\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 integrin in renal fibrosis. Gene set variation analysis was used to assess fibrotic gene signatures in human kidney biopsies. The therapeutic potential of MEDI8367, a monoclonal antibody targeting\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 integrin, was evaluated\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our findings demonstrate that\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 integrin is upregulated in the tubulointerstitium of CKD kidneys, particularly in diabetic kidney disease, and correlates with TGF-\n \u03b2<\/jats:italic>\n activation and renal function decline. MEDI8367 effectively inhibited\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8-mediated TGF-\n \u03b2<\/jats:italic>\n activation\n in vitro<\/jats:italic>\n and attenuated murine unilateral ureteral obstruction-induced renal fibrosis. Notably, inhibition of\n \u03b1<\/jats:italic>\n v\n \u03b2<\/jats:italic>\n 8 reduced kidney damage and improved kidney function in models of diabetic kidney disease and hypertensive nephropathy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our study highlights the potential of MEDI8367 to mitigate renal fibrosis and improve kidney function, offering a novel approach to CKD treatment that complements existing therapies.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001006","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T17:00:23Z","timestamp":1765558823000},"page":"942-954","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Targeting \u03b1v\u03b28 Integrin with mAb MEDI8367 Prevents Fibrosis in Preclinical Models of CKD"],"prefix":"10.34067","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2168-9810","authenticated-orcid":false,"given":"Elena","family":"Liarte Marin","sequence":"first","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Seth","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-3275","authenticated-orcid":false,"given":"David","family":"Baker","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-8193","authenticated-orcid":false,"given":"James","family":"Conway","sequence":"additional","affiliation":[{"name":"Bioinformatics, Oncology R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0141-4603","authenticated-orcid":false,"given":"Jean-Martin","family":"Lapointe","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9628-2708","authenticated-orcid":false,"given":"Richard","family":"Stebbings","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8175-1186","authenticated-orcid":false,"given":"Barbara","family":"Hebeis","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, 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