Salt Intake Research Articles

Non-communicable diseases (NCDs) have become a leading public health concern, contributing to significant morbidity and mortality worldwide. Among them, cardiovascular diseases (CVDs) are the most prevalent, accounting for 34% of total deaths in Sri Lanka. This research employs a quantitative research approach to analyze the demographic, behavioral, and socioeconomic factors influencing CVD prevalence in Sri Lanka. Using secondary data from the Ministry of Health and the 2021 Non-Communicable Diseases Risk Factor Survey, the study examines key variables to identify the associated risk. The findings indicate that demographic factors, including age and male sex, significantly increase CVD risk, while higher household income appears to have a protective effect. Regional disparities in CVD prevalence highlight the need for targeted interventions in high-risk areas. Lifestyle factors such as consumption of alcohol, tobacco use, physical inactivity, high salt and sugar intake, and diabetes history emerged as major contributors to CVD risk. The predictive model used in this study demonstrated strong capabilities in identifying high-risk individuals, making it a valuable tool for public health planning. The study underscores the importance of early screening, lifestyle modifications, and region-specific policy interventions to mitigate the growing burden of CVDs in Sri Lanka. Keywords: Non-Communicable Diseases (NCDs), cardiovascular disease (CVD), Risk Factors, Sri Lanka, Public Health

As we navigate through old age, it is essential to reflect on our health and routines. How do you feel each morning? Does your routine differ from when you were younger? Promoting healthy practices from childhood is crucial. Encouraging good nutrition, regular physical activity, and addressing mental health early on can significantly reduce the risk of chronic diseases in adulthood. I have witnessed this firsthand with my children, who are now parents themselves. From a young age, we emphasized the importance of dental visits and instilled healthy habits that support lifelong well-being. Starting early works. Research shows that early prevention is more effective than treatment once conditions manifest. Healthy childhood habits can significantly lower the risk of diseases like heart disease, diabetes, and obesity later in life. Public health initiatives are vital in this regard, as they play a key role in disease prevention. Regular health assessments, such as well-baby clinics, are essential to be sure that children are meeting the necessary milestones. Government approved pediatric vaccinations help prevent severe childhood diseases, while exercise, good nutrition, and timely treatment of infections are crucial for overall health. We must also be aware of conditions like obesity that can start early in life, leading to non-communicable diseases such as cardiovascular issues and diabetes. Monitoring growth progression in terms of weight and height against age is important. It is vital to avoid underfeeding or overfeeding children and to ensure they engage in adequate physical activity. To foster good dietary practices, such as consuming vegetables and limiting sugar, salt, and fat intake, we must start early. By focusing on these aspects, we can help our children develop healthy habits that last a lifetime.

Global deficiency of the dopamine D4 receptor (D4R) has been associated with kidney-related hypertension and salt sensitivity. To specifically investigate the role of D4R in renal tubules, we generated conditional knockout (CKO) mice using CRISPR/Cas9 to create Drd4-floxed homozygous mice, which were then crossed with CDH16-Cre transgenic mice to achieve tubular-specific deletion. In CKO mice (male, 4–5 months old), D4R expression was absent in renal tubules as confirmed by immunofluorescence staining. Immunoblotting of whole kidney homogenates revealed a significant reduction in D4R abundance (38 ± 4% of non-CKO levels; n = 5; Student’s t-test, p < 0.05). CKO mice maintained normal systolic blood pressure under standard salt(0.4% NaCl) intake but exhibited a >13% increase under high salt(4% NaCl) conditions (n = 15). Among the renal sodium transporters and channels evaluated, sodium-potassium-chloride cotransporter 2 (NKCC2: 218± 30%; n = 5) and sodium-chloride cotransporter (NCC: 241 ± 39%) were significantly elevated in CKO mice. No significant changes were observed in sodium-hydrogen exchanger 3, epithelial sodium channels, or Na + /K + -ATPase. Immunofluorescence further confirmed increased NCC expression in CKO kidneys, which colocalized with D4R in non-CKO mice. Administration of the NCC inhibitor hydrochlorothiazide elicited greater natriuretic and antihypertensive effects in CKO mice, indicating enhanced NCC activity. The increased NCC protein levels were accompanied by reduced NCC ubiquitination (47± 8%; n = 5). In vitro, D4R silencing in cultured mouse distal convoluted tubule (DCT) cells similarly increased NCC expression (155 ± 11%, n=4) and decreased its ubiquitination (43± 8%). Neither WNK4, Nedd4-2, components of the renin-angiotensin-aldosterone system, nor serum aldosterone levels were altered in CKO mice. However, the expression of ubiquitin-specific protease 48 (USP48), a deubiquitinating enzyme, was significantly increased in both the kidneys (169 ± 19%; n = 5) and DCT cells (202± 29%; n = 6) following Drd4 deficiency. Knockdown of USP48 via siRNA reduced NCC expression and increased NCC ubiquitination in vitro. In conclusion, renal tubular deletion of Drd4 results in salt-sensitive hypertension in mice, primarily through upregulation of NKCC2 and NCC. The deubiquitinating enzyme USP48 appears to mediate this effect by modulating NCC stability, suggesting a novel mechanism and potential therapeutic target for salt-sensitive hypertension.

Background: Digital therapeutics (DTx) for hypertension are one of the most promising hypertension treatments with proven antihypertensive effects. In this study, we investigated the predictors and prediction score of the home blood pressure (BP) lowering effect of DTx using the prospectively collected data on a daily basis. Methods: The B-INDEX is a multicenter intervention study with 6-month DTx, followed by 6 months without DTx in hypertensive patients. Home BP (morning and evening), body composition, physical activity, and sleep state were monitored using digital devices on a daily basis. This first report of the B-INDEX study analyzed data during a 6-month DTx treatment period. Results: A total of 198 hypertensive patients (mean age 54.9±10.6 years, 57.1% male, mean body mass index 26.7±5.3 kg/m 2 , 57.6% taking antihypertensive medication) were included in the analysis. A marked BP reduction was observed in the first 4 weeks (morning home BP: -6.2/-2.6mmHg). Mixed model analysis demonstrated that baseline home BP, older age, self-efficacy score, reduction of self-reported salt intake, and a mild initial drop of body weight (-500 g at week 4) were significant efficacy predictors of 6-month home BP reduction. The efficacy prediction score based on these predictors demonstrated a 10.2 mmHg difference in the home systolic BP reduction between higher vs lower score groups at week 24. Conclusions: Older age, salt reduction, and initial weight loss were predictive factors for effective BP reduction by DTx, independent of baseline BP values. We propose that the first 4 weeks are the key period for hypertension treatment with DTx.

The dysregulation of renal sodium metabolism linked to obesity and excessive dietary salt intake is a significant factor in the development of salt-sensitive hypertension. Our previous research has demonstrated that oxidative stress-particularly through the amplification loop of reactive oxygen species (ROS)-plays a critical role in modulating renal sodium handling via Na/K-ATPase signaling. This present study aims to determine whether the antioxidant enzyme heme oxygenase-1 (HO-1) modulates renal sodium metabolism by affecting oxidative stress and the Na/K-ATPase pathway, potentially revealing novel therapeutic avenues. To investigate this, we conducted high-salt dietary interventions and administered Co(III) protoporphyrin IX chloride (CoPP) in both normal and obese C57BL/6J mice. Results indicated that obesity exacerbated oxidative stress and disrupted sodium metabolism. Notably, the induction of HO-1 via CoPP effectively reduced oxidative stress, suppressed inflammatory responses, and modulated mechanisms of renal sodium handling. These observations were corroborated by decreases in protein carbonylation and malondialdehyde (MDA) levels, as well as inhibition of the IL-6/STAT3 inflammatory pathway. Importantly, up-regulation of HO-1 corresponded with a reduction in activated Na/K-ATPase signaling, likely attributable to diminished ROS levels. Furthermore, genetic analyses and urinary metabolite profiles validated the regulatory effects of CoPP on oxidative stress and sodium metabolism. In conclusion, our findings elucidate the dual role of HO-1 as both an antioxidant defense system and a pivotal modulator of sodium excretion. This research underscores the multifaceted physiological functions of HO-1 and its crucial role in regulating renal sodium metabolism, with significant implications for managing salt-sensitive hypertension.

IntroductionThe burden of cardiovascular disease in Sub-Saharan Africa has increased in recent years, and high blood pressure is the leading cause. One established risk factor for hypertension and cardiovascular disease is dietary salt intake. The World Health Organisation has highlighted low-sodium salt substitutes (LSSS) as a potential method to lower sodium intake. LSSS enriched with potassium may additionally support improving sodium-potassium balance. Studies in India and China have investigated the impact of LSSS on reducing sodium intake and the risk of stroke and hypertension in adults. However, evidence in African populations, and in particular youth, is lacking. As such, this protocol describes a phase 1 double-blinded randomised controlled trial to assess the efficacy of a potassium-enriched LSSS compared to traditional salt to improve urinary sodium-to-potassium ratio and blood pressure in African adolescents and their families.MethodsWe will enrol 600 adolescents (13–19 years old) and their primary caregivers living in Soweto, South Africa. Adolescents and their households will be randomised to receive a LSSS or traditional table salt (NaCl) for a 16-week period. All other household salt products will be removed. Anthropometrics and questionnaire data will be collected at 0 and 16 weeks. Spot urine samples and blood pressure will be collected at 0, 4, 12 and 16 weeks. Safety screening for kidney function will be conducted on household members at baseline. The trial protocol received ethics approval from the University of Witwatersrand Medical Human Research Ethics Committee (M221056).DiscussionThe obtained results will, to the best of our knowledge, be the first in an African population to provide insights into the efficacy of a potassium-enriched LSSS in improving urinary sodium-to-potassium ratio and blood pressure.Trial registrationThis trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za); identifier: PACTR202306727520808 (09 June 2023).Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09184-z.

Excessive dietary salt intake remains a critical and underestimated global health concern, strongly associated with increased cardiovascular disease risk. While the relationship between salt and arterial hypertension is well established, accumulating evidence highlights additional, blood pressure-independent mechanisms linking high salt intake with the progression of atherosclerosis. Beyond its hypertensive effects, high dietary salt directly damages the vascular endothelium by disrupting the glycocalyx, reducing nitric oxide synthesis, and increasing endothelial stiffness and inflammation. Excess sodium also impairs glycosaminoglycan buffering capacity and promotes immune cell adhesion, even in normotensive individuals. Furthermore, salt-induced dysbiosis of the gut microbiota alters the metabolic and inflammatory environment, lowering beneficial short-chain fatty acids and increasing pro-atherogenic metabolites such as trimethylamine N-oxide. Recent findings also implicate salt-driven modulation of hematopoiesis via Th17 cytokines, which enhances the production of pro-inflammatory monocytes that accelerate plaque development. These findings support the notion that high salt intake may be an independent and modifiable residual risk factor for atherosclerotic cardiovascular disease. Reducing dietary sodium—particularly from processed foods—should therefore remain a central component of both primary and secondary cardiovascular prevention. Although the optimal range of salt intake remains under discussion, a moderate reduction to below 5 g/day is considered safe and beneficial.

Digital therapeutics (DTx) for hypertension are among the most promising treatment options, demonstrating proven antihypertensive effects. This study investigates the determinants of the home blood pressure (BP) lowering effect of DTx, using prospectively collected daily data. The B-INDEX study (Behavioral Modification Index) is a multicenter intervention study in patients with hypertension, involving a 6-month DTx period, followed by an additional 6 months without it. Home BP, body weight and composition, physical activity, and sleep patterns were monitored daily using digital devices. This first report on B-INDEX analyzed data collected during a 6-month DTx treatment period. A total of 198 patients with hypertension (mean age, 54.9±10.6 years; 57.1% male; mean body mass index, 26.7±5.3 kg/m2; 57.6% taking antihypertensives) were included in the analysis. A marked reduction in BP was observed in the first 4 weeks (morning home BP, -6.2/-2.6 mm Hg). Mixed model analysis demonstrated that baseline home BP, older age, self-efficacy score, reduction in self-reported salt intake, and mild initial weight loss (-0.5 kg at week 4) were significant determinants of home BP reduction at 6 months. Older age, salt reduction, and initial weight loss were predictive factors for effective BP reduction through DTx, independent of baseline BP values. We propose that the first 4 weeks are the key period for hypertension treatment with DTx. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050479.

Objectives: Individuals with disabilities require targeted interventions to ameliorate disability-related conditions and improve overall health status. Nutritional challenges and counseling needs vary according to the type of disability, necessitating comprehensive assessments of dietary habits, physical activity, and food intake. Compared to traditional education, nutrition counseling offers a more sustainable and environmentally adaptable approach that effectively addresses individualized nutritional issues. Therefore, this study aimed to develop and evaluate a practical nutrition counseling manual and meal guidelines for people with disabilities in Korea, addressing their diverse dietary needs and improving nutritional care in social welfare facilities.Methods: A four-stage integrated research design was employed. Stage 1 involved qualitative research through in-depth interviews with 11 facility staff. In Stage 2, a nationwide survey (n = 249) was conducted based on the results of the interviews. Stage 3 integrated both qualitative and quantitative findings. Stage 4 focused on developing and evaluating a nutrition counseling manual and five types of meal guidelines through feedback from 26 nutritionists at 24 Korean Centers for Social Welfare Foodservice Management.Results: Six major nutrition counseling topics were identified: healthy eating, managing salt and sugar intake, dysphagia diet, appropriate intake, and hygiene. The manual and guidelines demonstrated high field usability, with average satisfaction scores of 3.98 and 3.99, respectively.Conclusion: The integrated study resulted in the development of a specialized nutrition counseling manual and handbook for individuals with disabilities in Korean social welfare facilities. The materials were revised and improved based on practical evaluations by dietitians, enhancing their field applicability. These tools are expected to contribute to better dietary management and health promotion among facility residents. The developed materials reflect the real-world needs of people with disabilities and offer practical tools for effective nutrition counseling and dietary management in institutional settings.

Abstract Background Cystinuria is a rare autosomal recessive disorder characterized by impaired renal reabsorption of cystine and dibasic amino acids, leading to recurrent nephrolithiasis. While dietary salt and protein restriction are commonly recommended, evidence supporting their effectiveness in reducing urinary cystine excretion is limited. This study investigated whether intra-individual changes in dietary salt and protein intake are associated with changes in cystine excretion over time. Methods We conducted a retrospective cohort study of 41 adult patients with recurrent cystine stones treated at a tertiary kidney stone clinic between 2004 and 2023. All patients underwent five 24-hour urine collections at intervals of 6–12 months. Urinary sodium and urea excretions were used as surrogates for salt and protein intake, respectively. Mixed-effects linear regression models assessed within-person associations between dietary intake and urinary cystine excretion, adjusting for age, sex, and time. Results Cystine excretion showed considerable intra-individual variability (intraclass correlation coefficient: 0.457). An increase in urinary urea of 3.5 g/24 h (reflecting ∼10 g/day higher protein intake) was associated with a 164 µmol/24 h increase in cystine excretion (95% CI: 57 to 271, p = 0.003). In contrast, a 17 mmol/24 h increase in urinary sodium (∼1 g/day salt intake) was associated with a non-significant 46 µmol/24 h increase in cystine excretion (95% CI: −5 to 97, p = 0.081). Conclusions Protein intake is moderately associated with urinary cystine excretion, whereas salt intake has minimal effect. These findings suggest that, while protein moderation may contribute to cystine reduction, fluid intake and urine alkalinization remain the primary determinants of urinary cystine levels.

Background: Reducing salt in bread is considered a straightforward, cost-effective public health intervention and is implemented in several countries, either voluntarily or through legislation. A Memorandum of Understanding (MoU) was signed in Greece in 2016, setting a voluntary maximum salt content of 1.2% in artisanal bread. This study aimed to evaluate the effectiveness of the MoU and assessed the potential impact of reducing salt in bread on overall salt intake, using the MoU target and the relevant WHO global sodium benchmark. Methods: Artisanal bread samples (n = 253) randomly collected from different parts of Greece in 2024 were analyzed for salt content and compared with samples collected in 2012 (n = 220). Salt intake from bread was estimated using data from the Hellenic National Nutrition and Health Survey (HNNHS), and modeling scenarios were conducted. Results: The MoU and related voluntary awareness activities were ineffective as a strategy to reduce salt in bread. The mean salt content in bread in 2024 was 1.41 (0.30)%, representing a 6.8% increase compared to 1.32 (0.31)% in 2012. Only 19.4% of samples in 2024 contained ≤1.2% salt, compared to 31.8% in 2012. Full MoU compliance would enable an additional 3.1% of Greek bread consumers, currently exceeding 5 g in their daily salt intake from foods alone, to reduce their intake to below 5 g. This would rise to 6.2% if the WHO sodium benchmark was implemented. Conclusions: A mandatory salt limit, aligned with the WHO global benchmark, is urgently needed to support national reformulation strategies. This work can contribute to European and international discussions on food reformulation.

High-salt intake exacerbates endolymphatic hydrops and alters aldosterone regulation in a Ménière's disease animal model.

Background/Objectives: Idiopathic edema (IE) in women is characterized by swelling of hands and face followed by increasing abdominal and truncal girth, bloating, edema, >1.4 kg weight gain when in upright posture, and nocturia that eliminates the retained fluid. A capillary leak is the primary pathophysiologic abnormality that induces different clinical presentations that were considered untreatable. Methods: We utilized different aspects of Starling forces of edema formation and treated four uncomplicated cases of IE by reducing salt intake with or without diuretics and two cases of life-threatening cases due to seizures and coma induced by acute hyponatremia in one and postural dizziness, fainting, and fractures and dislocations of joints in another. Results: All four uncomplicated cases of IE were treated by reducing salt intake with or without diuretics that eliminated the weight gain and nocturia. The patient with hyponatremia never developed hyponatremia by reducing water intake and signs and symptoms of IE by salt restriction and diuretic therapy and eliminated the postural hypotension, falls, and fainting by use of support hose that increased interstitial hydrostatic pressure to eliminate fluid shifting from intravascular to interstitial spaces. Conclusions: A leaky capillary induces pathophysiologic changes that activate different metabolic pathways. IE is now a treatable condition, following: 1. Salt restriction with or without diuretics for the cyclical weight gain, and 2. Water restriction for hyponatremia, hyponatremic seizures, and coma and 3. support hose for postural hypotension, postural dizziness, and fainting. IE is unrecognized and probably more common than it is perceived.

ObjectivesThis study aims to identify the key factors driving excessive alcohol and salt consumption in Ghana, both of which are modifiable risk factors for diseases such as cardiovascular conditions and cancers. Using the socio-ecological model (SEM), we qualitatively examine stakeholder perspectives to gain a comprehensive understanding of the influences contributing to these unhealthy consumption patterns.Design and methodsA qualitative study was conducted using semi-structured interviews. Transcripts were analysed thematically, with identified drivers mapped onto the corresponding levels of influence within the SEM.ParticipantsThe study included 21 purposively sampled stakeholders from government and academic institutions in Ghana, including policymakers, practitioners and researchers.ResultsDrivers of excessive salt and alcohol consumption were identified across all five levels of the SEM. At the intrapersonal level, disregard for health risks was a key factor. Community-level drivers included easy access to unhealthy foods and cultural norms promoting alcohol use at social events and salt in traditional dishes. At the societal and policy levels, inadequate regulation of the alcohol and food industries was found to reinforce lower-level drivers, further encouraging unhealthy consumption.ConclusionsThis study highlights the multilevel influences on alcohol and salt consumption, emphasising the interactions across SEM levels. It highlights that addressing unhealthy consumption is not solely a matter of personal responsibility, demonstrating that societal and policy factors play a significant role in shaping health and dietary behaviours. The findings underscore the need for comprehensive public health strategies that address influences at multiple levels to effectively reduce excessive alcohol and salt intake.

To evaluate to which extent patients with cardiovascular disease (CVD) report a diet in line with the Healthy Diet Characteristics recommended by the 2021 European Society of Cardiology guidelines on CVD prevention. To quantify the relationship between these diet characteristics and risk of cardiovascular events in patients with established CVD. Data from 2,553 patients with established CVD included in the UCC-SMART-cohort was used. Diet, except for salt intake, was quantified using a food frequency questionnaire. Cox regression adjusted for age, sex, lifestyle and energy-intake quantified the relationship between the Healthy Diet Characteristics and the risk of non-fatal vascular events (stroke and myocardial infarction). Patients (aged 59 ±9 years; 22% female; median body mass index 26kg/m2[25-75th percentile:24-29kg/m2] reported a diet which was in line with a median of 4 out of 11 Healthy Dietary Characteristics (25-75th percentile: 3-5). Fifty-eight percent reported eating at least 100 grams of fish per week. Sixteen percent reported a vegetable intake ≥200 grams/day, 12% a saturated fat intake below 10 energy-percent and 19% a more plant-based diet. Higher compliance with the Healthy Diet Characteristics was associated with a lower risk of non-fatal vascular events (209 events per 24,212 person-years; HR 0.89, 95%CI: 0.82-0.98) on average for each additional Healthy Dietary Characteristic. Patients with established CVD reported adhering to a median of 4 out of 11 Healthy Diet Characteristics and adhering to these was related to a lower risk of combined non-fatal stroke and myocardial infarction.

Disclosure: M. Kometani: asken.inc. Y. Oiwa: None. K. Aiga: None. Y. Noda: None. S. Konishi: None. D. Aono: None. M. Kadono: None. T. Yoneda: None.Background: Nutritional management for the elderly is essential for extending healthy life expectancy and improving quality of life (QOL). An appropriate nutrition intake particularly plays an important role in the prevention and management of chronic diseases. In recent years, the development of digital technology has made it possible to monitor nutrition intake using tools such as meal recording applications, and accumulate variety of evidence. However, detailed data on seasonal fluctuations in the nutritional intake of the elderly and deviations from nutritional intake standards are limited, and the impact of insufficient or excessive intake of salt or minerals on health risks has not been fully investigated. The aim of this study is to evaluate the nutrition intake status of people aged 65 years or older based on information obtained from diet and health management applications. Methods: This study analyzed users of a diet and health management application who were 65 years or older. Data were collected from November 2021 to November 2023. The evaluation criteria was set by nutrition intake and the rate of achievement of nutritional intake standards. The distribution of intake was also analyzed using box-and-whisker plots, and comparisons were made with the National Health and Nutritional Survey in Japan. The National Health and Nutrition Survey in Japan is an annual nationwide survey by the Ministry of Health, Labour and Welfare, assessing the health and nutritional intake of approximately 5,000 households. Results: A total of 9,385 participants met the criteria and were included in the final analysis. The analysis revealed seasonal fluctuations in the intake of major nutrients. Salt intake peaked in February, with a difference of 0.6g from August. In the analysis of the rate of achievement of nutritional intake standards in Japan, deficiencies in zinc and magnesium were particularly noticeable, at 15% for men and 21% for women, and 22% for men and 29% for women, respectively. Excessive salt intake was particularly noticeable, with 88% of men and 80% of women exceeding the standard. Conclusion: This study revealed seasonal fluctuations in nutrient intake and nutrient deficiencies through data analysis using an application. Of note, the increase in salt intake in winter and the deficiencies of magnesium and zinc are likely to be important issues for the elderly. These results could provide a basis for designing new approaches to the nutritional intake of the elderly using digital technology.Presentation: Monday, July 14, 2025

Chronic kidney disease (CKD) is a global health problem with a high economic burden and significant mortality. In Indonesia, the prevalence of CKD continues to rise, while cardiometabolic factors such as hypertension and diabetes, as well as certain infections (e.g., hepatitis B), are thought to contribute to disease progression in young adults. To determine the association between age, sex, hypertension, diabetes mellitus, and hepatitis B with CKD stage, and to identify the most influential factors in young adult patients. This was a retrospective study of medical records from patients aged 19-44 years at Rasyida Kidney Specialty Hospital, Medan, in 2024 (total sampling; n = 121). The dependent variable was CKD stage (stages 4-5). Univariate analysis was performed to describe patient characteristics; bivariate analysis (Fisher’s exact test) was used to assess the association between each factor and CKD stage; and multivariate logistic regression was used to determine independent predictors of advanced CKD. Of the 121 patients, 57% (69) were male, and the majority were aged 33-44 years (62.8%, n = 76). Stage 2 hypertension was present in 55.4% (67) of patients. A history of diabetes was found in 22.3% (27), with 18.2% (22) classified as prediabetic. Hepatitis B was identified in 10.7% (13). Bivariate analysis showed significant associations between CKD stage and hypertension (p < 0.001), diabetes (p < 0.001), and hepatitis B (p = 0.004), but no significant associations for sex (p = 0.052) or age (p > 0.05). Multivariate regression confirmed hypertension (p < 0.001), diabetes (p < 0.001), and hepatitis B (p= 0.033) as independent predictors of advanced CKD. In young adults, CKD stage is strongly associated with hypertension particularly stage 2 as well as diabetes mellitus and hepatitis B, while age and sex show no significant association. These findings highlight the importance of blood pressure screening and control, strict glycemic management, and hepatitis B treatment to slow CKD progression. Further studies are recommended to include lifestyle and metabolic factors such as BMI, dyslipidemia, salt intake, smoking, family history, and treatment adherence.

Abstract Background and Aims In 90%–95% of reported high blood pressure (BP) cases, the underlying cause cannot be determined. While textbook theory suggests that arterial hypertension is caused by sodium and water retention, pre-clinical evidence suggests that elevated blood pressure is part of a physiological-adaptive body response designed to prevent under-hydration, which occurs largely independent of salt intake level. To test whether this hypothesis also holds true in humans, we have quantified the effect of 24 h Na+ balance compared to the effect of 24 h water balance on morning systolic BP levels in healthy participants living in a controlled environment for 205 days, and then assessed the physiological parameters of body water conservation (plasma and urine osmolality, plasma solute distribution, free water clearance and urea metabolism) and tissue Na+ storage in patients with hypertension compared to healthy participants in a daily-life, observational setting. Method Mars500 was a mechanistic, ultra-long term balance study in which 6 healthy men living in an enclosed habitat for 205 days, who received a controlled diet with different salt intake levels (12 g/d, 9 g/d, 6 g/d) at constant energy intake, and collected 24 h urine daily. Sodium storage in Singaporeans (SSIS) is a clinical, cross-sectional study to study the association between tissue sodium storage, body water conservation and hypertension. Tissue Na+ (23 NaMRI), electrolytes, body hydration status and the nitrogen-driven water conservation (in blood and 24 h urine samples) were assessed and compared between healthy participants (n =79) and patients with essential hypertension (n =47). Results In participants living in a controlled environment, BP increased by 8 ± 1 mmHg when urine osmolality was high, and fluid intake or urine volume was low. This BP-increasing water conservation response was not caused by body Na+ retention. Similarly, participants living under daily-life conditions showed large variability in individual 24 h Na+ excretion, which was uncoupled from blood pressure levels. Instead, hypertensive participants showed adaptive body water conservation with increased plasma solute concentration (300.7 ± 4.8 vs 298.4 ± 4.5 mmol/l, p < 0.01) and reduced renal free-water clearance (−8.1 ± 2.1 vs −3.1 ± 1.2 ml/kg/d, p < 0.05) at similar urine volume level. This increase in plasma osmolality was explained by an increase in urea and glucose solutes (p < 0.05), while the contribution of Na+ solutes was decreased. Metabolomics analysis in the 24 h urine showed increased levels of urea cycle metabolites citrulline (18.9 ± 20.0 vs 8.7 ± 7.3 mmol/d, p < 0.001), ornithine (29.3 ± 26.1 vs 17.1 ± 12.1 mmol/d, p < 0.001) and arginine (27.4 ±21.3 vs 21.1 ± 14.8 mmol/d, p < 0.05), as well as arginino-succinate (13.2 ± 5.8 vs 9.9 ± 3.9 mmol/d, p < 0.001), confirming increased urea production in hypertensive participants. Higher BP levels were accompanied by increased skin Na+ storage (19.1 ± 4.6 vs 16.8 ± 3.9 mmol/l tissue, p < 0.01), without changes in plasma Na+ concentration or 24 h Na+ excretion. Conclusion BP increase in humans is part of a systemic, nitrogen-driven body water conservation response designed to prevent dehydration, which occurs largely independent of body Na+ balance. These findings provide a novel pathophysiological view on the relationship between body fluid homeostasis and the development of essential hypertension. Trial registration number: ClinicalTrials.gov (NCT04319068).

Background: Symptoms of dizziness, syncope, and palpitations are common presentations in outpatient and emergency care, frequently attributed to stress and anxiety when conventional neurological and cardiac evaluations are normal. Joint hypermobility (JH) syndromes including hypermobile Ehlers–Danlos syndrome (hEDS), and hypermobility spectrum disorders (HSD) are under-recognised as potential causes. Methods: Our retrospective cohort study examined the clinical features, diagnostic findings, and responses to treatment in patients with JH syndromes, who are referred to a specialised syncope clinic within a UK teaching hospital. It involved 218 patients with joint hypermobility, predominantly young females (median Beighton score: 6), reporting chronic orthostatic intolerance, dizziness, and palpitations. Common comorbidities included joint pain, chronic fatigue, gastrointestinal dysmotility, and psychiatric conditions. Prevalence of symptoms, cardiovascular abnormalities on investigation (ECG, echocardiography, and tilt-table testing), and treatment responses were analysed. Results: History and examination were often diagnostic. Standard cardiac tests rarely provided diagnostic value except to exclude alternate conditions. Tilt-table testing was abnormal in 82.0% of cases, revealing orthostatic hypotension, reflex syncope, or postural tachycardia syndrome (POTS). Conservative measures (hydration, salt intake, and exercise) were effective in over half of the cases; pharmacological treatments (ivabradine, fludrocortisone) were considered for refractory cases. Conclusions: This study emphasises that JH syndromes are a common cause of palpitations, dizziness, and syncope in young females. They are multi-system conditions affecting both physical and mental health, which remain under-recognised and are often dismissed as ‘functional’, particularly in women—highlighting gender bias in diagnosis. A structured diagnostic approach with routine joint assessments for JH and increased awareness can facilitate early recognition and management in general medical settings, reducing reliance on emergency services and improving patient outcomes.

Excess salt intake is a major modifiable risk factor for hypertension and cardiovascular disease. Personalized interventions using genetic information and digital tools, such as smartphone applications, may enhance sodium reduction, but evidence remains limited. To evaluate the effectiveness of a sodium reduction program incorporating a genetic profile and an artificial intelligence (AI)-based mobile app among adults with elevated blood pressure and a sodium-sensitive genotype. A 3-arm randomized clinical trial, conducted at a Japanese electronics company from September 17 to December 16, 2024, included employees aged 20 to 65 years with elevated blood pressure and the sodium-sensitive AGT M235T genotype. Participants were randomized on a 1:1:0.2 basis to (1) a treatment group receiving a genetic profile and an AI-based app incorporating sodium-specific information; (2) a control group receiving no intervention; or (3) an app-only group using the app without a genetic profile or information. The primary outcome was daily salt intake, estimated from spot urine samples using the INTERSALT (International Study of Electrolyte Excretion and Blood Pressure) formula. Secondary outcomes included self-reported body mass index, behavior change intentions, and systolic and diastolic blood pressure. Analysis was performed on an intention-to-treat basis. Of 312 randomized participants, 289 completed follow-up (mean [SD] age, 51.3 [8.3] years; 252 of 279 men [90.3%]). The mean (SD) baseline salt intake was 11.3 (2.0) g/d. At 3 months, no significant difference in salt intake was observed between the treatment and control groups (mean difference, -0.2 g/d; 95% CI, -0.7 to 0.3 g/d) or between the treatment and app-only groups (mean difference, -0.04 g/d; 95% CI, -0.9 to 0.8 g/d). No significant differences were observed between groups in any secondary outcomes. In this randomized clinical trial conducted among individuals with elevated blood pressure and a sodium-sensitive genotype, a sodium reduction program combining a genetic profile and an AI-based app with sodium-specific information did not significantly reduce salt intake. These findings highlight the challenges of achieving dietary behavior change through genetic personalized plus digital interventions. http://umin.ac.jp/ctr Identifier: UMIN000052685.