{"doi":"10.3389/fnut.2025.1538962","title":"The impact of high-salt diet and diuretics on the development of the aestival phenomenon in patients with chronic heart failure","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—a 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>±</jats:monospace> 22.1 mg, torasemide 7.4 <jats:monospace>±</jats:monospace> 3 mg, and spironolactone 42 <jats:monospace>±</jats:monospace> 12.4 mg. Biochemical parameters<jats:monospace>—</jats:monospace>including sodium, potassium, glucose, urea, and estimated plasma osmolality (eOSM)<jats:monospace>—</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> = 0.039), 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> = 0.012). The PropUrea/eOSM increased to 2.63% [1.89; 3.28] in the diuretic group compared to 2.00% [1.70; 2.50] (p = 0.011). Conversely, PropNa/eOSM decreased to 46.46% [46.02; 46.74] versus 46.68% [46.33; 46.89] (<jats:italic>p</jats:italic> = 0.050). Multivariate logistic regression confirmed that diuretic therapy was independently associated with these changes: PropUrea/eOSM (OR = 3.52, 95% CI: 1.94<jats:monospace>–</jats:monospace>7.26, <jats:italic>p</jats:italic> &amp;lt; 0.001), and PropNa/eOSM (OR = 0.16, 95% CI: 0.06<jats:monospace>–</jats:monospace>0.39, <jats:italic>p</jats:italic> &amp;lt; 0.001). These effects were most pronounced in patients consuming &amp;gt;10 g/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—especially when combined with high sodium intake—is 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 g/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>","journal":"Frontiers in Nutrition","year":2025,"id":640165,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1663676,"name":"Anna V. Sokolova","orcid":null,"position":1,"is_corresponding":false},{"id":1663677,"name":"Vadim M. Mitrokhin","orcid":null,"position":2,"is_corresponding":false},{"id":1663678,"name":"Grigory P. Arutyunov","orcid":null,"position":3,"is_corresponding":false},{"id":1663675,"name":"Dmitrii O. Dragunov","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The impact of high-salt diet and diuretics on the development of the aestival phenomenon in patients with chronic heart failure","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—a 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>±</jats:monospace> 22.1 mg, torasemide 7.4 <jats:monospace>±</jats:monospace> 3 mg, and spironolactone 42 <jats:monospace>±</jats:monospace> 12.4 mg. Biochemical parameters<jats:monospace>—</jats:monospace>including sodium, potassium, glucose, urea, and estimated plasma osmolality (eOSM)<jats:monospace>—</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> = 0.039), 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> = 0.012). The PropUrea/eOSM increased to 2.63% [1.89; 3.28] in the diuretic group compared to 2.00% [1.70; 2.50] (p = 0.011). Conversely, PropNa/eOSM decreased to 46.46% [46.02; 46.74] versus 46.68% [46.33; 46.89] (<jats:italic>p</jats:italic> = 0.050). Multivariate logistic regression confirmed that diuretic therapy was independently associated with these changes: PropUrea/eOSM (OR = 3.52, 95% CI: 1.94<jats:monospace>–</jats:monospace>7.26, <jats:italic>p</jats:italic> &amp;lt; 0.001), and PropNa/eOSM (OR = 0.16, 95% CI: 0.06<jats:monospace>–</jats:monospace>0.39, <jats:italic>p</jats:italic> &amp;lt; 0.001). These effects were most pronounced in patients consuming &amp;gt;10 g/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—especially when combined with high sodium intake—is 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 g/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>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40765740","pmcid":"PMC12321533","openalex_id":"https://openalex.org/W4412544703","authors":[],"funders":[],"total_grants":0,"fwci":2.3277,"citation_percentile":0.88727563,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1538962/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1538962/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fnut.2025.1538962/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fnut.2025.1538962","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40765740","host_type":"repository"},{"url":"https://doaj.org/article/b5571ffafa4f4d1da99b744c1863e295","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12321533","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12321533","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12321533?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Electrolyte and hormonal disorders","Sodium Intake and Health","Thermoregulation and physiological responses","Medicine"],"mesh_terms":[],"keywords":["Diuretic","Furosemide","Medicine","Internal medicine","Heart failure","Osmolyte","Endocrinology","Urea","Renal function","Spironolactone","Chemistry","Biochemistry","Aestivation","Osmolytes","Diuretics","Plasma Osmolality","chronic heart failure","Sodium Intake"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T07:11:35.944309Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}