ArticleThe Journal of clinical investigation2017
High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 114 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Natriuretic-ureothelic Adaptation of Body Fluid Homeostasis During SGLT-2 Inhibition and/or Mineralocorticoid Receptor Modulation in Patients With Chronic Kidney Disease. A 4-arm, Double-blind, Double-dummy, Parallel-group, Phase 2 Study to Investigate the Mechanistic Effects of Dapagliflozin, Dapagliflozin + Balcinrenone, Balcinrenone and Placebo on Body Solute and Water Homeostasis and Energy Metabolism in Male and Female Participants Over 50 Years of Age With Chronic Kidney Disease.
Effect of Reduced Sodium Chloride in Fluid Creep and Maintenance Fluids in Critically Ill Adults: A Randomized Controlled Trial
Who cites it
114 citing papers in PubMed, 198 citations in OpenAlex.
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- High dietary salt intake increases urinary NGAL excretion and creatinine clearance in healthy young adults.American journal of physiology. Renal physiology · 2022Trial
- Increased Salt Intake Decreases Diet-Induced Thermogenesis in Healthy Volunteers: A Randomized Placebo-Controlled Study.Nutrients · 2022Trial
- Effect of high-salt diet on blood pressure and body fluid composition in patients with type 1 diabetes: randomized controlled intervention trial.BMJ open diabetes research & care · 2020Trial
- Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.JCI insight · 2020Trial
- Effects of Sodium Reduction on Energy, Metabolism, Weight, Thirst, and Urine Volume: Results From the DASH (Dietary Approaches to Stop Hypertension)-Sodium Trial.Hypertension (Dallas, Tex. : 1979) · 2020Trial
- Metabolic control by liver-kidney crosstalk and glucagon in health and disease.Nature reviews. Nephrology · 2026Review
- Role of estimated salt intake and nutritional status in patients undergoing hemodialysis: a longitudinal analysis.BMC nephrology · 2026Observational
- Pharmacokinetics and Metabolomic Mechanism of the Diuretic Effects of Barbatic Acid fromBiology · 2026Article
- Preliminary evidence of extrarenal sodium storage in a large mammal: implications for comparative physiology and hypertension research : Running: Sodium storage in cattle.Pflugers Archiv : European journal of physiology · 2026Article
- Metabolic Alterations Associated With Diet and Hypertension in Rats.Journal of nutrition and metabolism · 2026Article
- NaCl and urea modulate CD8+ T cell survival, renal accumulation, and response to BK virus.JCI insight · 2025Article
- High Salt Intake Affects Visceral Adipose Tissue Homeostasis: Beneficial Effects of GLP-1 Agonists.Biology · 2025Article
- Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load.Intensive care medicine experimental · 2025Article
- Sodium Balance and Quality of Life in People with Chronic Kidney Disease-A Cross-Sectional Study.Nutrients · 2025Article
- Kidney immunology from pathophysiology to clinical translation.Nature reviews. Immunology · 2025Review
- Life-supporting functional kidney replacement by integration of embryonic metanephros-bladder composite tissue transplants.Kidney international · 2025Article
- Changes in microbial and metabolic profiles of mice fed with long-term high salt diet.BMC gastroenterology · 2025Article
- Mechanistic study of the effect of a high-salt diet on the intestinal barrier.Scientific reports · 2025Article
- The impact of high-salt diet and diuretics on the development of the aestival phenomenon in patients with chronic heart failure.Frontiers in nutrition · 2025Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 4 countries.
Funding
Abstract
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.