{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:54Z","timestamp":1789103274947,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) lacks accessible, cost-effective biomarkers for early screening. Given the distinct clearance pathways of free prostate-specific antigen (FPSA, renally excreted) and total prostate-specific antigen (TPSA, hepatically metabolized), this study investigated the association between serum FPSA\/TPSA ratio and estimated glomerular filtration rate (eGFR) in male patients with type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this real-world cross-sectional study, 4,487 male patients with T2DM were retrospectively enrolled. eGFR was determined using the Kidney Disease: Improving Global Outcomes (KDIGO)-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C (Cr-CysC) equation. Multivariable linear regression and subgroup analyses were conducted to elucidate the independent effect of the FPSA\/TPSA ratio on eGFR, with adjustment for age, prostate-specific diseases, and metabolic confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline TPSA levels remained stable across renal function stages (median 0.9ng\/ml, P\u00a0=\u00a00.524), minimizing interference from macroscopic prostate pathologies. After adjustment for age and metabolic profiles, the FPSA\/TPSA ratio exhibited a robust independent negative association with eGFR (\u03b2 = \u22120.2, P &amp;lt; 0.001). This inverse correlation remained consistent across all clinical subgroups (P for interaction &amp;gt; 0.05), with a more pronounced predictive trend among elderly patients (\u2265 65 years). Notably, our multivariable models also captured the chronic kidney disease \u201clipid paradox\u201d, whereby higher triglyceride levels paradoxically correlated with preserved eGFR (\u03b2 = 0.51, P\u00a0=\u00a00.018).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An elevated serum FPSA\/TPSA ratio is a robust, non-invasive indicator of declining eGFR in male patients with T2DM and may improve DKD risk stratification and early clinical warning without additional economic burden.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1905743","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:34:53Z","timestamp":1789101293000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing a prostate tumor marker: elevated FPSA\/TPSA ratio as a novel non-invasive biomarker for declining eGFR in male type 2 diabetes"],"prefix":"10.3389","volume":"17","author":[{"given":"Shihua","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Zibo Central Hospital","place":["Zibo, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zibo Central Hospital","place":["Zibo, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zibo Central Hospital","place":["Zibo, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Qingdao Endocrine & Diabetes Hospital","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deying","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zibo Central Hospital","place":["Zibo, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.06.024","article-title":"Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment","volume":"98","author":"de Boer","year":"2020","journal-title":"Kidney Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2012070718","article-title":"Kidney disease and increased mortality risk in type 2 diabetes","volume":"24","author":"Afkarian","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.7326\/l23-0070","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"S219","DOI":"10.2337\/dc25-s011","article-title":"11. 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