{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:49:31Z","timestamp":1782103771601,"version":"3.54.5"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007928","name":"Ningbo Municipal Bureau of Science and Technology","doi-asserted-by":"publisher","award":["2023J020, 2023-2026"],"award-info":[{"award-number":["2023J020, 2023-2026"]}],"id":[{"id":"10.13039\/501100007928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["WKJ-ZJ-26084"],"award-info":[{"award-number":["WKJ-ZJ-26084"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"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>To evaluate and identify urinary biomarkers for the early diagnosis and staging of diabetic kidney disease (DKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 200 participants, including healthy controls (NDM, n=50) and patients with type 2 diabetes. The diabetic patients were stratified by urinary albumin-to-creatinine ratio (ACR) into the following groups: normoalbuminuria (SDM, n=50), microalbuminuria (MADKD, n=50), and macroalbuminuria (ADKD, n=50). Utilizing an integrated multi-dimensional screening strategy, we systematically evaluated traditional urinary protein markers (urinary retinol\u2212binding protein [URBP], urinary immunoglobulin G [UIgG], urinary transferrin [UTRF], urinary alpha\u22121\u2212microglobulin [U\u03b11\u2212MG], and urinary beta\u22122\u2212microglobulin [U\u03b22\u2212MG]), 20 urinary amino acids, and urinary proteins identified via high-throughput mass spectrometry. Candidate proteins were validated by ELISA, and their diagnostic performance was assessed using ROC curve analysis, with ACR serving as the practical clinical reference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the traditional urinary protein markers, UTRF and UIgG demonstrated excellent diagnostic value, with areas under the curve (AUC) of 0.926 and 0.916, respectively. Among the amino acids, PRO showed the best diagnostic performance (AUC\u00a0=\u00a00.746). However, when all 20 urinary amino acids were combined into a diagnostic model, it exhibited outstanding diagnostic value (AUC\u00a0=\u00a00.928), outperforming individual amino acids and even traditional protein markers. From the top 50 proteins identified in the proteomic screening, serpin family A member 1 (SERPINA1) was determined to be a key protein. Subsequent ELISA validation and ROC analysis further confirmed that SERPINA1 possesses outstanding diagnostic capability (AUC\u00a0=\u00a00.964, 95% CI: 0.936\u20130.990), significantly outperforming other candidate proteins, namely osteoclast\u2212associated Ig\u2212like receptor (OSCAR), contactin 1 (CNTN1), and CD58 molecule (CD58).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Traditional proteins, especially UTRF\/UIgG, hold diagnostic value. The 20-amino-acid combination (AUC\u00a0=\u00a00.928) outperformed them. This study first systematically identifies urinary SERPINA1 as a highly promising DKD biomarker, offering a novel target for early diagnosis and precise management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1859999","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:36:01Z","timestamp":1782102961000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mining biomarkers for type 2 diabetic nephropathy based on urinary proteomics and metabolomics"],"prefix":"10.3389","volume":"17","author":[{"given":"Mindong","family":"Mi","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhuan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Third School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyong","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunguang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital 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