{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T20:04:23Z","timestamp":1786824263654,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"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>Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease (ESRD) worldwide, primarily affecting individuals with Type 2 Diabetes Mellitus (T2DM). While traditional risk factors\u2014such as hypertension, poor glycemic control, and dyslipidemia\u2014are well known, recent research has illuminated the pivotal role of inflammation in DN pathogenesis. Inflammatory processes involving chemokines, cytokines, immune cell infiltration, and pro-fibrotic signaling pathways (e.g., NF\u03baB, JAK\/STAT) contribute significantly to glomerular and tubulointerstitial damage. Key immune players include macrophages and T lymphocytes, particularly CD4+ T cells, which correlate with disease severity and progression. Serum Amyloid A (SAA), an acute-phase reactant traditionally associated with Serum Amyloid A Amyloidosis (AA amyloidosis), has emerged as both a biomarker and active mediator of renal inflammation in DN. SAA promotes cytokine release, leukocyte recruitment, and extracellular matrix remodeling, contributing to glomerular and tubular injury. Elevated Saa3 expression in experimental models correlates with DN progression, while activation of the advanced glycation end products and the receptors for advanced glycation end products (AGE\u2013RAGE) axis in podocytes enhances SAA upregulation and inflammatory signaling. Increasing evidence now indicates that SAA functions, not only as a marker of systemic inflammation, but also as a mechanistically significant driver of intrarenal injury, bridging metabolic dysregulation with sustained inflammatory and fibrotic signaling. Emerging therapeutic approaches\u2014including interleukin 6 (IL-6) blockade, inhibition of AGE formation, targeted anti-fibrotic agents, and recently developed SAA-directed RNA or peptide therapeutics\u2014underscore the therapeutic potential of modulating SAA activity in DN. Preclinical evidence further supports the efficacy of monoclonal antibodies, signaling inhibitors, and dietary anti-inflammatory compounds in mitigating renal injury. Collectively, these developments position SAA as a central mediator at the intersection of metabolic, inflammatory, and fibrotic pathways, highlighting its promise as both a diagnostic biomarker and a therapeutic target for early intervention in diabetic kidney disease.<\/jats:p>","DOI":"10.3390\/jcm14238427","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:19:51Z","timestamp":1764328791000},"page":"8427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Inflammatory Role of Serum Amyloid A in the Pathogenesis and Progression of Diabetic Nephropathy"],"prefix":"10.3390","volume":"14","author":[{"given":"Antigoni","family":"Stavrou","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9241-8620","authenticated-orcid":false,"given":"Christina A.","family":"Kousparou","sequence":"additional","affiliation":[{"name":"School of Medicine, European University Cyprus, 6 Diogenes Street, 2404 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyrios","family":"Tsakalis","sequence":"additional","affiliation":[{"name":"School of Medicine, European University Cyprus, 6 Diogenes Street, 2404 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.2337\/diabetes.50.12.2842","article-title":"A Nonlinear Effect of Hyperglycemia and Current Cigarette Smoking Are Major Determinants of the Onset of Microalbuminuria in Type 1 Diabetes","volume":"50","author":"Scott","year":"2001","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.4062\/biomolther.2020.204","article-title":"Diabetic Nephropathy\u2014A Review of Risk Factors, Progression, Mechanism, and Dietary Management","volume":"29","author":"Natesan","year":"2021","journal-title":"Biomol. 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