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Disulfiram (DSF), an approved treatment for alcohol dependence, has recently emerged as an inhibitor of innate immune responses such as pyroptosis. In this study, we investigated whether DSF attenuates kidney injury in adenine\u2010induced nephropathy and explored the underlying mechanisms. DSF treatment markedly ameliorated kidney injury in adenine\u2010induced nephropathy, accompanied by suppression of inflammatory cell infiltration and inflammasome\u2010 and pyroptosis\u2010related markers. RNA sequencing revealed restoration of disrupted fatty acid metabolism in the kidneys following DSF treatment. Furthermore, DSF alleviated DNA damage, cellular senescence, and fibrosis. Importantly, activation of gasdermin D, a central executor of pyroptosis, was closely associated with disease severity in human CKD biopsy samples, supporting the clinical relevance of this pathway. Collectively, these findings suggest a potential role for DSF in modulating inflammatory and immunometabolic pathways in CKD.<\/jats:p>","DOI":"10.1096\/fj.202601271rr","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:11:45Z","timestamp":1789629105000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disulfiram Attenuates Adenine\u2010Induced Renal Fibrosis by Modulating Inflammatory and Immunometabolic Responses"],"prefix":"10.1096","volume":"40","author":[{"given":"Saori","family":"Kin","sequence":"first","affiliation":[{"name":"Department of Nephrology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8558-8832","authenticated-orcid":false,"given":"Yuji","family":"Oe","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Graduate School of Medicine 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