{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:19:14Z","timestamp":1785417554807,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015763","name":"University of Szeged","doi-asserted-by":"publisher","award":["8711"],"award-info":[{"award-number":["8711"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"publisher"}]},{"award":["8711"],"award-info":[{"award-number":["8711"]}],"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Hyperuricemia has long been linked to the progression of chronic kidney disease (CKD), although the role of serum uric acid (sUA) reduction in kidney preservation remains uncertain. Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower sUA levels and exert renoprotective effects, but it is unclear whether these findings are mechanistically related. Methods: Adult patients with type 2 diabetes mellitus and hyperuricemia were included from a retrospective cohort. Patients treated with empagliflozin (n = 70) or dapagliflozin (n = 78) were pooled into a single group and compared with an allopurinol-treated group (n = 66). Exploratory mediation-informed analysis models assessed associations between treatment, changes in sUA (\u0394sUA), and changes in estimated glomerular filtration rate (\u0394eGFR) at 12 and 36 months. Dose\u2013response and nonlinear associations between \u0394sUA and \u0394eGFR were additionally examined. Results: At 12 months, SGLT2 inhibitor treatment was associated with greater \u0394sUA compared with allopurinol (B = 22.62, p = 0.040); its direct association with \u0394eGFR remained significant after adjustment for \u0394sUA (B = \u22126.14, p &lt; 0.001). At 36 months, the association of treatment with \u0394sUA was no longer significant, whereas association with \u0394eGFR persisted (B = \u221211.8, p &lt; 0.001). No dose\u2013response or nonlinear relationship was identified between \u0394sUA and \u0394eGFR, while treatment remained an independent predictor of \u0394eGFR at both time points. Conclusions: Reductions in sUA do not appear to mediate the renoprotective effects of SGLT2 inhibitors. The preservation of kidney function associated with SGLT2 inhibitor therapy is likely driven by mechanisms independent of sUA lowering.<\/jats:p>","DOI":"10.3390\/medsci14040421","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Mediation-Informed Analysis and Dose\u2013Response Analysis of Uric Acid Reduction and Kidney Outcomes in SGLT2 Inhibitor Therapy Compared to Allopurinol"],"prefix":"10.3390","volume":"14","author":[{"given":"Tam\u00e1s","family":"J\u00e1mbor","sequence":"first","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Internal Medicine, H\u00f3dmez\u0151v\u00e1s\u00e1rhely-Mak\u00f3 Healthcare Center, 6900 Mak\u00f3, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs P\u00e9ter","family":"Tall\u00f3sy","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5081-7313","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Lantos","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Informatics, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3139-0235","authenticated-orcid":false,"given":"Andrea","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2508-6014","authenticated-orcid":false,"given":"Roland","family":"Fejes","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Internal Medicine, H\u00f3dmez\u0151v\u00e1s\u00e1rhely-Mak\u00f3 Healthcare Center, 6900 Mak\u00f3, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e346","DOI":"10.1016\/S2665-9913(25)00344-3","article-title":"Worldwide trends in hyperuricaemia from 2000 to 2023: A systematic review and modelling analysis","volume":"8","author":"Nkeck","year":"2026","journal-title":"Lancet Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132527","DOI":"10.1016\/j.ijcard.2024.132527","article-title":"Uric acid and metabolic syndrome: Importance of hyperuricemia cut-off","volume":"417","author":"Maloberti","year":"2024","journal-title":"Int. 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