{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:16:53Z","timestamp":1787894213246,"version":"build-2784847793"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research (KAKENHI) program","doi-asserted-by":"publisher","award":["23K07672"],"award-info":[{"award-number":["23K07672"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Distinguishing glomerulonephritis (GN) from diabetic kidney disease (DKD) and nephrosclerosis (NS) is clinically important. Urinary uromodulin (uUMOD), a biomarker of renal tubular integrity, may help discriminate among these chronic kidney disease (CKD) etiologies. We evaluated the diagnostic utility of uUMOD for differentiating GN from DKD and NS. Methods: This retrospective single-center study included 90 patients with biopsy-proven GN (n = 30), DKD (n = 25), or NS (n = 35). First-morning spot urine samples obtained before biopsy were analyzed for uUMOD concentration and normalized to urinary creatinine levels (uUMOD\/Cr). Results: The uUMOD\/Cr ratio was significantly higher in GN (21.2 mg\/gCr [10.3\u201331.3]) than in DKD (5.5 [3.6\u201312.3], p &lt; 0.001) or NS (10.7 [6.4\u201319.9], p = 0.021). In multivariate analyses adjusted for age, sex, estimated glomerular filtration rate, interstitial fibrosis, and urinary protein, the uUMOD\/Cr ratio was independently associated with GN (p = 0.003) and this correlation remained statistically significant after additional adjustment for diabetes mellitus. Receiver operating characteristic curve analysis showed an area under the curve value of 0.833 for GN versus DKD, 0.714 for GN versus NS, and 0.764 for GN versus DKD and NS combined. A cutoff value of 16.5 mg\/gCr yielded 72.8% sensitivity and 70.0% specificity for identifying GN. Conclusions: uUMOD secretion is preserved in GN compared to DKD or NS and shows moderate diagnostic utility for differentiating between these biopsy-proven CKD etiologies. uUMOD may serve as a simple, noninvasive biomarker when biopsy is difficult or clinical findings are inconclusive.<\/jats:p>","DOI":"10.3390\/diagnostics16172741","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:32Z","timestamp":1787756672000},"page":"2741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Uromodulin for Distinguishing Between Glomerulonephritis, Diabetic Kidney Disease, and Nephrosclerosis in a Biopsy-Proven Cohort"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-6015","authenticated-orcid":false,"given":"Tomoaki","family":"Takata","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Mae","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Kawata","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Fujino","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sosuke","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Iyama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Hoi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tahira","sequence":"additional","affiliation":[{"name":"Advanced Medicine, Innovation and Clinical Research Center, Tottori University Hospital, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Isomoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guo, J., Jiao, W., Xia, S., Xiang, X., Zhang, Y., Ge, X., and Sun, Q. (2025). The global, regional, and national patterns of change in the burden of chronic kidney disease from 1990 to 2021. BMC Nephrol., 26.","DOI":"10.1186\/s12882-025-04028-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s10157-021-02049-0","article-title":"Estimating the prevalence of definitive chronic kidney disease in the Japanese general population","volume":"25","author":"Nagai","year":"2021","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tawara-Iida, T., Usui, J., Ebihara, I., Ishizu, T., Kobayashi, M., Maeda, Y., Kobayashi, H., Kobayashi, T., Ueda, A., and Tsuchida, M. (2022). Study protocol and baseline characteristics of newly induced dialysis patients: A prospective multi-center cohort study with a biological sample bank, the Ibaraki Dialysis Initiation Cohort (iDIC) study. BMC Nephrol., 23.","DOI":"10.1186\/s12882-022-02729-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0140-6736(25)01942-7","article-title":"Chronic kidney disease","volume":"407","author":"Herrington","year":"2026","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1046\/j.1523-1755.2000.00031.x","article-title":"Renoprotective benefits of RAS inhibition: From ACEI to angiotensin II antagonists","volume":"57","author":"Taal","year":"2000","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.kint.2022.08.012","article-title":"Diabetes management in chronic kidney disease: A consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"102","author":"Khunti","year":"2022","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Takata, T., and Isomoto, H. (2021). Pleiotropic effects of sodium-glucose Cotransporter-2 inhibitors: Renoprotective mechanisms beyond glycemic control. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094374"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1001\/jama.2025.9532","article-title":"Delaying Progression of Chronic Kidney Disease","volume":"334","author":"Song","year":"2025","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1053\/j.ajkd.2012.02.330","article-title":"Bleeding complications of native kidney biopsy: A systematic review and meta-analysis","volume":"60","author":"Corapi","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"(2024). Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., 105, S117\u2013S314.","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"358","DOI":"10.33160\/yam.2024.11.005","article-title":"Managing dosage adjustments in pseudo-Hypocreatinemia: Insights from vancomycin-induced nephrotoxicity in a sarcopenic patient","volume":"67","author":"Taniguchi","year":"2024","journal-title":"Yonago Acta Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yamada, K., Takata, T., Iyama, T., Hamada, S., Mae, Y., Sugihara, T., and Isomoto, H. (2022). Fluorescence imaging using enzyme-activatable probes for detecting diabetic kidney disease and glomerular diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158150"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1111\/nep.13720","article-title":"Urinary exosomes: Potential biomarkers for diabetic nephropathy","volume":"25","author":"Sinha","year":"2020","journal-title":"Nephrology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/s41598-020-58067-7","article-title":"Urinary peptidomics and bioinformatics for the detection of diabetic kidney disease","volume":"10","author":"Brondani","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Takata, T., Hisatome, I., and Isomoto, H. (2026). Hyperuricemia in chronic kidney disease: Clinical evidence and the missing role of urinary uric acid handling. Intern. Med.","DOI":"10.2169\/internalmedicine.7918-26"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2169\/internalmedicine.1342-22","article-title":"The versatile role of uromodulin in renal homeostasis and its relevance in chronic kidney disease","volume":"63","author":"Takata","year":"2024","journal-title":"Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2215\/CJN.06390420","article-title":"What does uromodulin do?","volume":"16","author":"Kipp","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Takata, T., Hamada, S., Mae, Y., Iyama, T., Ogihara, R., Seno, M., Nakamura, K., Takata, M., Sugihara, T., and Isomoto, H. (2022). Uromodulin regulates murine Aquaporin-2 activity via thick ascending limb-collecting duct cross-talk during water deprivation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169410"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.2215\/CJN.03600318","article-title":"Uromodulin and nephron mass","volume":"13","author":"Pivin","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mae, Y., Takata, T., Ida, A., Ogawa, M., Taniguchi, S., Yamamoto, M., Iyama, T., Fukuda, S., and Isomoto, H. (2020). Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for renal outcomes in patients with rapidly progressive glomerulonephritis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041128"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhou, J., Chen, Y., Liu, Y., Shi, S., Wang, S., Li, X., Zhang, H., and Wang, H. (2013). Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071023"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Watanabe, K., Sato, E., Mishima, E., Miyazaki, M., and Tanaka, T. (2022). What\u2019s new in the molecular mechanisms of diabetic kidney disease: Recent advances. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010570"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.kint.2022.05.012","article-title":"Molecular mechanisms and therapeutic targets for diabetic kidney disease","volume":"102","author":"Tuttle","year":"2022","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0891-6632(91)90037-P","article-title":"Tamm-Horsfall-Protein excretion as a marker of ascending limb transport indicates early renal tubular damage in diabetes mellitus type I","volume":"5","author":"Zimmerhackl","year":"1991","journal-title":"J. Diabet. Complicat."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Thielemans, R., Speeckaert, R., Delrue, C., De Bruyne, S., Oyaert, M., and Speeckaert, M.M. (2023). Unveiling the hidden power of uromodulin: A promising potential biomarker for kidney diseases. Diagnostics, 13.","DOI":"10.3390\/diagnostics13193077"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2215\/CJN.04230415","article-title":"Associations of urinary uromodulin with clinical characteristics and markers of tubular function in the general population","volume":"11","author":"Pruijm","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12094","DOI":"10.1038\/s41598-020-69077-w","article-title":"A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe","volume":"10","author":"Iyama","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000500833","article-title":"Diagnostic performance of retinopathy in the detection of diabetic nephropathy in type 2 diabetes: A systematic review and meta-analysis of 45 studies","volume":"62","author":"Jiang","year":"2019","journal-title":"Ophthalmic Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/ndt\/12.12.2588","article-title":"Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus","volume":"12","author":"Mak","year":"1997","journal-title":"Nephrol. Dial. Transplant."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2741\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:23:39Z","timestamp":1787891019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":30,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16172741"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16172741","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}