{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:30:33Z","timestamp":1791909033540,"version":"4.3.4"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007638","name":"Kidney Foundation, Japan","doi-asserted-by":"publisher","award":["JKFB21-18"],"award-info":[{"award-number":["JKFB21-18"]}],"id":[{"id":"10.13039\/501100007638","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jichi Medical University Young Investigator Awards","award":["JKFB21-18"],"award-info":[{"award-number":["JKFB21-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>We previously reported that sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and\/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (\u22121.4 \u00b1 31.5% vs. 31.5 \u00b1 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin\u2013angiotensin\u2013aldosterone and sympathetic nervous systems.<\/jats:p>","DOI":"10.3390\/diagnostics14111194","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T11:50:09Z","timestamp":1717588209000},"page":"1194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sodium\u2013Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction"],"prefix":"10.3390","volume":"14","author":[{"given":"Maki","family":"Asakura-Kinoshita","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6893-7188","authenticated-orcid":false,"given":"Takahiro","family":"Masuda","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"},{"name":"Department of Nephrology, Shin-Oyama City Hospital, Oyama 3230827, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Oka","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"},{"name":"Department of Nephrology, Shin-Oyama City Hospital, Oyama 3230827, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Ohara","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shin-Oyama City Hospital, Oyama 3230827, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Morinari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nasu Minami Hospital, Nasu-Karasuyama 3210621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyohei","family":"Misawa","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"},{"name":"Department of Nephrology, Shin-Oyama City Hospital, Oyama 3230827, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nasu Minami Hospital, Nasu-Karasuyama 3210621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shin-Oyama City Hospital, Oyama 3230827, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Nagata","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 3290498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-physiol-031620-095920","article-title":"Effects of Sglt2 Inhibitors on Kidney and Cardiovascular Function","volume":"83","author":"Vallon","year":"2021","journal-title":"Annu. 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