{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:24:33Z","timestamp":1786973073371,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. Given the significant adverse effects and inconsistent long-term efficacy of conventional immunosuppressive strategies, there is an unmet need for safer adjunctive therapies. Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as potential candidates to address this therapeutic gap. Purpose: This narrative review summarizes the proposed mechanisms of action of omega-3 PUFAs in IgAN and critically evaluates the current clinical evidence regarding their therapeutic potential and limitations. Mechanisms: Emerging experimental data suggest that omega-3 PUFAs may modulate inflammatory and fibrotic pathways relevant to kidney injury. Proposed mechanisms include modulation of eicosanoid metabolism, attenuation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and generation of specialized pro-resolving mediators. In experimental studies, omega-3 PUFAs may also suppress nuclear factor kappa B (NF-\u03baB)-driven transcription and attenuate mesangial cell proliferation, IgA immune-complex deposition, and transforming growth factor beta 1 (TGF-\u03b21)\/Smad3-mediated fibrotic signaling. Clinical Evidence: Conclusions: Omega-3 PUFAs have biological plausibility as adjunctive therapy in IgAN, but their clinical benefit remains uncertain. Available randomized trials and meta-analyses suggest possible modest effects on proteinuria in some settings, whereas evidence for preservation of kidney function or prevention of kidney failure is inconsistent and of low certainty. Future well-designed trials incorporating guideline-directed background therapy and biomarker-guided patient selection are essential to determine optimal dosing, formulation, biological exposure, and whether any patient subgroups derive clinically meaningful benefit.<\/jats:p>","DOI":"10.3390\/jcm15166332","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"6332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Omega-3 Fatty Acids in IgA Nephropathy: An Updated Review of Mechanisms and Evidence"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-4779","authenticated-orcid":false,"given":"Hulya","family":"Taskapan","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-9253","authenticated-orcid":false,"given":"Luxcia","family":"Kugathasan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Labib","family":"Faruque","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3K9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabo","family":"Sikaneta","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Scarborough Health Network, Toronto, ON M1P 2V5, Canada"},{"name":"Department of Family and Community Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Scarborough Health Network, Toronto, ON M1P 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group, Rovin, B.H., Barratt, J., Cook, H.T., Noronha, I.L., Reich, H.N., Suzuki, Y., Tang, S.C., Trimarch, H., and Floege, J. 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