{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:25:11Z","timestamp":1792621511912,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic heart failure (CHF) often requires the use of high-dose loop diuretics to achieve decongestion. However, such therapy may lead to adverse effects, including deterioration of renal function and electrolyte imbalance. Recent evidence suggests that diuretic-induced dehydration may trigger metabolic responses resembling aestivation\u2014a survival mechanism involving a shift from inorganic to organic osmolytes, particularly increased urea synthesis, to conserve water.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective, single-center cohort study included 102 patients (median age 75 years, 57.8% female) hospitalized with CHF from January to July 2023. The diuretic group received average daily doses of furosemide 39.1 <jats:monospace>\u00b1<\/jats:monospace> 22.1\u202fmg, torasemide 7.4 <jats:monospace>\u00b1<\/jats:monospace> 3\u202fmg, and spironolactone 42 <jats:monospace>\u00b1<\/jats:monospace> 12.4\u202fmg. Biochemical parameters<jats:monospace>\u2014<\/jats:monospace>including sodium, potassium, glucose, urea, and estimated plasma osmolality (eOSM)<jats:monospace>\u2014<\/jats:monospace>were assessed on days 1 and 7 of hospitalization. Plasma osmolyte ratios (PropUrea\/eOSM, PropNa\/eOSM) were calculated. Propensity score matching (PSM) was used to adjust for confounders such as age, ejection fraction, and renal function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By day 7, plasma osmolality in the diuretic group increased from 300 [297; 304] to 302.2 [298.3; 305.8] mOsm\/L (<jats:italic>p<\/jats:italic> =\u202f0.039), while no significant change occurred in the non-diuretic group. Urea levels rose to 7.95 [5.65; 9.90] mmol\/L in the diuretic group versus 5.90 [5.05; 7.50] mmol\/L in the control group (<jats:italic>p<\/jats:italic> =\u202f0.012). The PropUrea\/eOSM increased to 2.63% [1.89; 3.28] in the diuretic group compared to 2.00% [1.70; 2.50] (p\u202f=\u202f0.011). Conversely, PropNa\/eOSM decreased to 46.46% [46.02; 46.74] versus 46.68% [46.33; 46.89] (<jats:italic>p<\/jats:italic> =\u202f0.050). Multivariate logistic regression confirmed that diuretic therapy was independently associated with these changes: PropUrea\/eOSM (OR\u202f=\u202f3.52, 95% CI: 1.94<jats:monospace>\u2013<\/jats:monospace>7.26, <jats:italic>p<\/jats:italic> &amp;lt;\u202f0.001), and PropNa\/eOSM (OR\u202f=\u202f0.16, 95% CI: 0.06<jats:monospace>\u2013<\/jats:monospace>0.39, <jats:italic>p<\/jats:italic> &amp;lt;\u202f0.001). These effects were most pronounced in patients consuming &amp;gt;10\u202fg\/day of salt.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated that in patients with chronic heart failure (CHF), intensive loop diuretic therapy\u2014especially when combined with high sodium intake\u2014is associated with a shift in plasma osmolytes, marked by increased urea and reduced sodium contributions to osmolality. These changes suggest activation of water-conservation mechanisms and are independent of CHF severity or renal dysfunction, as confirmed by propensity score matching. Clinically, the urea-to-osmolality ratio may serve as an early marker of metabolic stress and muscle catabolism. Patients consuming &amp;gt;10\u202fg\/day of salt appear especially susceptible to this aestivation-like response. Early identification of these changes may guide adjustments in diuretic regimens, as well as prompt nutritional and physical interventions to mitigate sarcopenia and functional decline. These findings support a personalized approach to diuretic therapy in CHF, emphasizing the role of dietary sodium in shaping metabolic responses and highlighting metabolic aestivation as a potential contributor to fatigue and weakness in this population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1538962","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T04:10:37Z","timestamp":1753157437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The impact of high-salt diet and diuretics on the development of the aestival phenomenon in patients with chronic heart failure"],"prefix":"10.3389","volume":"12","author":[{"given":"Dmitrii O.","family":"Dragunov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Sokolova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim M.","family":"Mitrokhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigory P.","family":"Arutyunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000164149","article-title":"Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry","volume":"113","author":"Peacock","year":"2008","journal-title":"Cardiology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1056\/NEJMoa1005419","article-title":"Diuretic strategies in patients with acute decompensated heart 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