{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:08:33Z","timestamp":1788959313231,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai General Hospital Discipline Construction Project","award":["0206012418"],"award-info":[{"award-number":["0206012418"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Hyperuricemic nephropathy (UAN) involves a systemic thromboinflammatory axis, yet the role of antithrombin (AT, SERPINC1) remains incompletely defined. While AT has anticoagulant and anti-inflammatory properties, whether it contributes to UAN as a disease-responsive molecular node remains uncertain. Methods: We integrated two-sample MR of serum urate and renal traits with complementary sensitivity analyses, cis-eQTL and pQTL analyses of SERPINC1, and exploratory transcriptomic, proteomic, metabolomic, and coexpression analyses. The available data were used to assess genetic associations and to distinguish genetic evidence from cross-dataset molecular patterns. Results: Genetically predicted serum urate showed positive or negative associations with BUN and eGFR, respectively, but the primary analyses showed substantial heterogeneity. Reverse-direction estimates were also associated with serum urate, representing reciprocal genetic relationships between related renal traits and urate rather than proof of a temporal feedback cycle. Available data did not demonstrate mediation through genetically predicted whole-blood SERPINC1 expression. Three deCODE cis-pQTL instruments gave inconsistent renal estimates: nominally lower BUN (\u03b2 = \u22120.0290, p = 0.047), null eGFR (\u03b2 = \u22120.0036, p = 0.472), and higher CKD risk (\u03b2 = +0.3361, p = 0.020) with directional pleiotropy evidence. Exploratory multi-omics analyses showed higher PBMC SERPINC1 expression during acute gout and a nominal urinary proteomic difference that did not survive multiple-testing correction (FDR = 0.998). Conclusions: SERPINC1 is best interpreted as a responsive molecular feature requiring further validation, rather than as a demonstrated genetic mediator or renal-protective therapeutic target. The transcriptomic and urinary findings represent cross-dataset, stage-associated observations and should not be interpreted as proven sequential phases.<\/jats:p>","DOI":"10.3390\/genes17091084","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:26:11Z","timestamp":1788956771000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Urate and Renal Dysfunction: Bidirectional Genetic Associations, External Validation, and Exploratory Multi-Omics Characterization of Antithrombin (SERPINC1) in Hyperuricemic Nephropathy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1137-0966","authenticated-orcid":false,"given":"Lei","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Immunology & Allergy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Immunology & Allergy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.kint.2020.10.015","article-title":"Does gouty nephropathy exist, and is it more common than we think?","volume":"99","author":"Piani","year":"2021","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"\u021a\u0103poi, L., \u0218alaru, D.L., Sasc\u0103u, R., and St\u0103tescu, C. 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