{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:53:43Z","timestamp":1783018423289,"version":"3.54.6"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Conventional biomarkers such as estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) primarily reflect glomerular damage and often fail to detect early tubular injury. Consequently, patients with \u201cnon-albuminuric diabetic kidney disease (DKD)\u201d may be overlooked. This study evaluated the independent association between urinary post-translationally modified fetuin-A fragments (uPTM-FetA) and DKD risk stratification in Japanese patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a cross-sectional study of 219 outpatients with type 2 diabetes between November 2023 and February 2024 at Edogawa Hospital. First-morning urine samples were analyzed for uPTM-FetA and urinary liver-type fatty acid-binding protein (uL-FABP) using enzyme-linked immunosorbent assays. DKD risk was classified into four categories based on the KDIGO guidelines. The association between uPTM-FetA and higher DKD-risk (categories 2\u2009+\u20093\u2009+\u20094) was assessed using multiple logistic regression and restricted cubic spline (RCS) analyses, validated by bootstrapping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The optimal cutoff value for uPTM-FetA was determined to be 11.76 ng\/mgCr. Multivariable analysis adjusted for potential confounders revealed that high uPTM-FetA levels were significantly and independently associated with DKD-risk categories 2\u2009+\u20093\u2009+\u20094 (adjusted odds ratio: 3.88; 95% CI: 2.02\u20137.45; P\u2009&lt;\u20090.01). RCS analysis indicated a significant non-linear association (P\u2009=\u20090.04). Notably, high uPTM-FetA was detected in 38.8% of patients with normoalbuminuria and 42.0% of those with preserved eGFR. A striking discrepancy was observed compared to uL-FABP: while high uL-FABP was completely absent (0.0%) in patients within the low-to-moderate risk categories (categories 1 and 2), high uPTM-FetA was observed in 34.0% and 60.8% of these patients, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>uPTM-FetA is independently associated with DKD severity and is elevated in a substantial proportion of patients with early-stage disease where conventional markers remain normal. Unlike uL-FABP, which increases predominantly in advanced stages, uPTM-FetA appears to identify tubular stress earlier. Thus, uPTM-FetA serves as a valuable complementary biomarker to uACR for refining DKD risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353032","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:46:10Z","timestamp":1783014370000},"page":"e0353032","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of urinary post-translationally modified fetuin-A fragments with diabetic kidney disease risk stratification in Japanese patients with type 2 diabetes"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2104-3990","authenticated-orcid":true,"given":"Toshiko","family":"Mori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8143-0082","authenticated-orcid":true,"given":"Hiroyuki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Kozasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizuko","family":"Yukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzuko","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Antoku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"pone.0353032.ref001","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.2337\/dc14-1296","article-title":"Diabetic 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