{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:36:05Z","timestamp":1772998565605,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22zf0127006"],"award-info":[{"award-number":["JP22zf0127006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Originally developed as glucose\u2010lowering agents for type 2 diabetes, sodium\u2013glucose cotransporter\u20102 (SGLT2) inhibitors have recently attracted attention for their kidney\u2010protective effects in patients with diabetic kidney disease (DKD). However, their underlying metabolic mechanisms remain unclear. We, therefore, hypothesized that non\u2010invasive urinary metabolite profiling could provide novel mechanistic insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We comprehensively analysed urinary volatile organic compounds (VOCs) in patients with DKD using gas chromatography\u2013mass spectrometry. A total of 61 patients were enrolled, including those treated with SGLT2 inhibitors and untreated individuals. Overall, 79 urinary VOCs were identified and quantified; clinical variables were examined using appropriate statistical methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 61 patients, those treated with SGLT2 inhibitors showed significantly higher urinary levels of acetone and 2\u2010pentanone compared with untreated individuals. These metabolites are derived from ketone bodies, suggesting enhanced ketogenesis in the treated group. The increase in these VOCs was consistent across patients and was not explained by differences in other baseline clinical characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that SGLT2 inhibitor therapy is associated with elevated urinary ketone\u2010related VOCs, reflecting a shift in systemic energy metabolism. These observations contribute to a better understanding of the metabolic mechanisms underlying the kidney\u2010protective effects of SGLT2 inhibitors. Considering that urinary VOCs can be measured non\u2010invasively, this approach holds promise for future research and clinical monitoring of treatment effects in DKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.70176","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:11:43Z","timestamp":1771463503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>SGLT2<\/scp>\n                    Inhibitor\u2010Associated Changes in Urinary Volatile Organic Compounds in Diabetic Kidney Disease: A Comprehensive Study"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9455-5596","authenticated-orcid":false,"given":"Risa","family":"Hara","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyasu","family":"Yamahara","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Graduate School of Engineering The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-0935","authenticated-orcid":false,"given":"Toyohiro","family":"Hashiba","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huang","family":"Keying","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Graduate School of Engineering The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Graduate School of Engineering The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo 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