{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:41:59Z","timestamp":1792773719309,"version":"4.5.0"},"reference-count":90,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney Blood Press Res"],"abstract":"<jats:p>&lt;p&gt;Background: The pathogenesis of hyperuricemic nephropathy (HN) is increasingly linked to a self-perpetuating cycle of thromboinflammation. This process begins with hyperuricemia-induced endothelial dysfunction, which activates both the coagulation cascade and inflammatory pathways, notably the pyrin domain-containing protein 3 inflammasome. This creates a vicious cycle of which inflammation promotes coagulation and coagulation products further amplify inflammation, ultimately leading to renal microvascular thrombosis, ischemia, and progressive fibrosis. Summary: This review critically examines the therapeutic potential of antithrombin (AT) in interrupting this pathogenic axis. AT, a key serine protease inhibitor, is central to physiological anticoagulation. Beyond its canonical role in neutralizing thrombin and factor Xa (FXa), AT exerts potent anti-inflammatory and endothelial-stabilizing effects, primarily mediated through interactions involving its D-helix domain. Compelling preclinical evidence from models of sepsis, ischemia-reperfusion, and diabetic nephropathy demonstrates that AT can attenuate inflammation, improve microcirculation, and reduce fibrosis. We hypothesize that in HN, augmenting AT levels may simultaneously dampen thrombin generation, quell the associated inflammatory response, and protect the endothelium, thereby potentially mitigating the structural drivers of renal decline. These findings suggest that AT might serve as a multi-target candidate for disease modification, pending validation in HN-specific models. Notably, this hypothesis remains untested in HN-specific models, with current evidence extrapolated from related thromboinflammatory conditions. Therefore, this review synthesizes the mechanistic rationale, clearly delineates established science from translational hypothesis, and identifies the crucial experimental gaps \u2013 particularly regarding optimal dosing, timing, and direct validation of efficacy in HN \u2013 that must be addressed to evaluate the potential of AT repurposing as a candidate targeted therapy for hyperuricemic kidney injury.&lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/kbr\/adjag005","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:52:58Z","timestamp":1788616378000},"page":"887-902","source":"Crossref","is-referenced-by-count":0,"title":["Antithrombin in Hyperuricemic Nephropathy: Unveiling Its Noncanonical Renoprotective Roles and Therapeutic Repurposing 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