Dietary Salt Restriction Research Articles

Using Doppler duplex ultrasound to determine hemodynamic alterations in renal vasculature: Crucial pathophysiological event preceding renal dysfunction in decompensated cirrhosis

BackgroundRenal dysfunction is a watershed event in cirrhosis, often preceded by renal vasoconstriction. However, our reliability on elevated serum creatinine often delays interventions. Measurement of Renal Resistive Index (RI) and Renal Venous Stasis Index (RVSI) by Doppler ultrasound offers insight into renal vasoconstriction. MethodsFifty participants with decompensated cirrhosis with ascites and normal serum creatinine underwent renal Doppler ultrasound for the measurement of RI and RVSI. All patients were compliant with a salt-restricted diet. Individuals aged <18 years, hepatocellular carcinoma, non-cirrhosis-related ascites, pre-existing renal disease, obstructive uropathy, or history of nephrotoxic medication use were excluded. Statistical analyses, including Pearson correlation, regression analysis, and Chi-square/Fisher’s exact tests, were performed to assess the statistical significance between RI, RVSI, and renal parameters. Additionally, the association of RI with the model for end-stage liver disease sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores was also assessed. ResultsMajority were males (88%), average CTP score was 11.7, mean MELD-Na score was 20.92, and mean serum creatinine was 1.05 mg/dL. Renal parameters had varying RI values among renal arteries, with the main right and left arteries at 0.615 [standard deviation (SD): 0.089] and 0.638 (SD: 0.083), respectively. RI and RVSI are significantly correlated with serum creatinine. Further, significant correlation between, RI, RVSI values noted with MELD-Na score even when serum creatinine values are normal. ConclusionStrong correlations between serum creatinine, RI, and MELD-Na scores hints at predictive clinical potential. Future research with larger cohorts and extended follow-up is required to gauge clinical utility and its impact on outcomes.

Multicenter, open label, randomized controlled superiority trial for availability to reduce nocturnal urination frequency: The TOP-STAR study.

Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. This multicenter, open-label, randomized, parallel-group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half-life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time-shift effect of the short half-life tofogliflozin and salt restriction on urinary time. The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half-life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

Apical tubular complement activation and the loss of kidney function in proteinuric kidney diseases.

Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function.

#1526 Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic review and meta-analysis of randomized controlled trials

Abstract Background and Aims To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Method We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN. Literature searching was performed via PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of the reference lists. Systematic reviews and meta-analyses of RCTs that evaluated the effects of any dietary intervention on clinical outcomes of DN were included. Two reviewers evaluated the methodological quality of the included articles through AMSTAR score. In addition, according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as “high”, “moderate”, “low” or “very low” quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories (class I to IV and non-significant (NS)). Results We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles (Fig. 1). Moderate quality evidence suggested that probiotics supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in DN patients. Low quality evidence indicated that probiotics supplementation significantly improved serum creatinine, urinary albumin creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low quality evidence suggested that a salt restriction diet could significantly improve creatinine clearance rate (CrCl) in patients with DN. Low quality evidence suggested that vitamin D supplementation could significantly improve UACR in patients with DN. Besides, low quality evidence indicated that soy isoflavone supplementation could significantly improve BUN, FBG, TC, triglycerides (TG) and LDL-C in patients with DN. Furthermore, low quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low quality evidence suggested supplementation of antioxidant vitamins could significantly improve serum creatinine, systolic blood pressure, and HbA1c in patients with DN. The remaining outcomes were rated as very low quality due to significant risk of bias, significant heterogeneity, imprecision, and publication bias. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence (Fig. 2). Conclusion Moderate to low evidence suggests that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, and salt-restricted diets may significantly improve clinical outcomes in patients with DN.

POTASSIUM-ENRICHED SALT EFFECTIVELY REDUCES SODIUM INTAKE IN THE NURSING HOME POPULATION OF NORTHERN CHINA: THE CHINA SALT TRIAL

Objective: to explore the promoting effect of long-term consumption of potassium-enriched salt (KCL/NACL=1:1) on dietary salt restriction in the nursing home population. Design and method: In northern China, a total of 29 nursing homes were selected using cluster random sampling. The nursing homes were divided into intervention group (using potassium-enriched salt in the dining room) and control group (using regular salt in the dining room). The usage of salt and high-sodium condiments in the dining room was recorded, including the amount of salt used and the number of diners. The average per capita daily sodium intake from condiments (TNA/PD) in the nursing home was calculated, as well as the average per capita daily sodium intake from dietary salt (SNA/PD). The two values were added together to calculate the total per capita daily sodium intake (ANA/PD). Results: Over 6 years, a total of 18,046 meals were consumed in the dining room. The intervention group demonstrated a significant reduction in per capita daily sodium intake (ANA/PD) compared to the control group (3.0 vs 5.0g). There was no statistically significant difference in per capita daily sodium intake from condiments (TNA/PD) between the two groups, but the intervention group exhibited a significantly lower per capita daily sodium intake from dietary salt (SNA/PD) compared to the control group (2.2 vs 4.1g). Furthermore, the intervention group consistently maintained a lower urine sodium-to-potassium ratio than the control group. By incorporating potassium-enriched salt, the intervention group achieved an average increase of 1.2±0.31g in daily potassium intake. Subgroup analysis of 24-hour urine results indicated that the intervention group had significantly lower urinary sodium excretion and higher potassium excretion. Following one year of using potassium-enriched salt, the estimated dietary salt intake in the intervention group decreased from approximately 15g to around 9g based on urinary sodium excretion. Conclusions: These findings suggest that the utilization of potassium-enriched salt can effectively reduce sodium intake without necessitating alterations in dietary habits.

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Hepatic hydrothorax.

Hepatic hydrothorax (HH) refers to the presence of a pleural effusion that develops in the context of underlying liver cirrhosis and portal hypertension. It carries a high risk of morbidity and mortality, with a median survival of 8-12 months. Diagnosis is usually confirmed by pleural aspiration, demonstrating typical features of a transudative effusion in the absence of co-existent cardio-pulmonary or renal pathology. The clinical presentation is quite variable, with some patients remaining relatively asymptomatic in the presence of small or incidental effusions, while others present with frank respiratory failure requiring pleural intervention. The development of spontaneous bacterial empyema (SBEM) is a significant and not infrequent complication, requiring prompt recognition and treatment. While the mainstay of management is focused on optimising fluid balance through dietary salt restriction and diuretic therapy, liver transplantation remains the definitive treatment option. As such, it is crucial to adopt a multi-disciplinary approach-involving pulmonologists, hepatologists, dieticians, and palliative care physicians-in order to optimise care for this often complex group of patients. This review will discuss the basic pathophysiology of HH, its clinical presentation and diagnosis, as well as the approach to management of HH in clinical practice, focussing on both interventional and non-interventional treatment modalities.

Dietary Salt Restriction and Adherence to the Mediterranean Diet: A Single Way to Reduce Cardiovascular Risk?

The dietary restriction of salt intake and the adhesion to Mediterranean dietary patterns are among the most recommended lifestyle modifications for the prevention of cardiovascular diseases. A large amount of evidence supports these recommendations; indeed, several studies show that a higher adherence to Mediterranean dietary patterns is associated with a reduced risk of cardiovascular disease. Likewise, findings from observational and clinical studies suggest a causal role of excess salt intake in blood pressure increase, cardiovascular organ damage, and the incidence of cardiovascular diseases. In this context, it is also conceivable that the beneficial effects of these two dietary patterns overlap because Mediterranean dietary patterns are typically characterized by a large consumption of plant-based foods with low sodium content. However, there is little data on this issue, and heterogeneous results are available on the relationship between adherence to salt restriction and to Mediterranean dietary patterns. Thus, this short review focuses on the epidemiological and clinical evidence of the relationship between the adherence to Mediterranean dietary patterns and dietary salt restriction in the context of cardiovascular risk.

Association of dietary salt intake with diabetes mellitus in the Japanese general population

Abstract Background/Introduction Excess salt intake, one of the most important modifiable factors in our lifestyle, has been reported to be a risk of cardiovascular morbidity and mortality. Several mechanisms underlying the development of cardiovascular disease after excess salt intake are proposed, among which hypertension has been established. Diabetes mellitus (DM) is also a risk factor of cardiovascular disease and, thus, there may be some association between excess salt intake and DM. Purpose The present study was designed to investigate possible relationship between dietary salt intake and DM in the general population. Methods Dietary salt intake was estimated using a spot urine sample in 16018 subjects (male=9642, 52.0±12.3 year-old) who visited our hospital for a yearly physical checkup from July 2008 to March 2019 (baseline). A cross-sectional analysis for the relationship between salt intake and DM was performed at baseline. Then, subjects without DM (n=14715, male=8651, 51.3±12.3 year-old) were followed up until March 2020 (median 2107 days) with the endpoint being the development of DM. DM was defined as fasting plasma glucose (FPG) ≥126mg/dL, HbA1c≥6.5% or the use of antidiabetic medications. Results A cross-sectional analysis revealed that salt intake in subjects was 8.67±1.98 g/day. Salt intake was significantly higher in subjects with (n=1280) than without DM (9.55±2.17 vs. 8.61±1.94 g/day). Multivariate regression analysis adjusted for age, gender, body weight, systolic blood pressure, pulse rate, serum creatinine, uric acid, FPG, LDL-cholesterol, triglyceride, current smoking and frequent alcohol drink showed that salt intake was associated with the presence of DM (r=0.027, p&amp;lt;0.001). In the follow-up study, 861 subjects developed DM (10.1 per 1000 person-year), with the incidence being more frequent in males than in females (11.7 vs. 7.6 per 1,000 person-year). The incidence of DM was increased across the quartiles of salt intake at baseline (7.5, 7.6, 10.5 and 14.8 per 1000 person-year). In analysis where salt intake at baseline was taken as continuous variables, non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the new onset of DM was 1.146 (1.109-1.184). Multivariate Cox-hazard analysis adjusted for possible risk factors showed that salt intake was a significant predictor for the future development of DM (HR: 1.037, 95%CI: 1.001-1.073), while additional adjustment for baseline body weight disappeared the statistical significance (HR: 0.994, 95%CI: 0.958-1.031). Conclusions Salt intake is associated with the development of DM and excess salt intake may predict future development of DM in the general population. Excess food intake which is usually accompanied by excess salt intake in individuals with increased body weight may be responsible for the development of DM. Maintenance of appropriate body weight as well as restriction of dietary salt may lead to the prevention from developing DM.

A Spanish Family with Gordon Syndrome Due to a Variant in the Acidic Motif of WNK1.

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS.

A Rare Presentation of Acute Coronary Syndrome, in a Patient of Amputation of Right Forearm: A Case Study.

A patient presented with sudden onset right-sided chest pain in the emergency department. He had a past history of amputation of his right forearm due to trauma 25 years back. Phantom limb pain was suspected, but on investigations, he was diagnosed with acute coronary syndrome with unstable angina. The patient was treated in ICCU ECG and ECHO were done.ECG report showed T wave inversion in V3-V6 precordial leads with ST elevation (fixed change). A coronary angiogram was done and minor CAD was detected(LAD minor blockage). ECHO report showed mild tricuspid regurgitation, concentric LVH, EF-64%. Blood pressure was 150/90mm Hg, pulse rate-103/minute and Trop T was negative on admission in iccu. The patient’s lipid profile, thyroid function test, kidney function tests, FBS, and PPBS was done and reports were normal.. Patient on discharge was advised oral medications like aspirin. clopidogrel, atorvastatin, angiotensin receptor blocker and nitroglycerine tablets. On discharge salt-restricted diet and two weeks of bed rest were advised. The theory of past experiences, denervation hypersensitivity and cortical plasticity might be the contributors of such atypical angina pain presentation which overruled the dermatomal rule. The study highlighted on atypical presentation of ACS as cardiac pain radiated in the right side in a special scenario of amputation of the right upper limb below the elbow. Differential diagnosis : Costochondral chest pain, Dextrocardia, Pericarditis, pneumonia, esophageal disease. The phantom limb component of referred pain radiates to the right side

#4797 ASSOCIATION BETWEEN BLOOD PRESSURE AND SALT CONSUMPTION WITH FLUID STATUS USING BIOIMPEDANCE SPECTROSCOPY IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Control of extracellular volume in peritoneal dialysis (PD) patients requires both removal of sodium and water. Hypervolemia occurs more frequently in PD patients and is associated with greater morbidity and mortality. Dietary salt restriction (Na+ &amp;lt; 2g) is recommended in all PD patients. Most patients do not comply with this recommendation (prevalence difficult to assess). Bioimpedance spectroscopy (BIS) devices can help assess volume overload in patients receiving maintenance PD. The aim of our study was to determine the association between fluid status as measured using BIS to BP and salt consumption in continuous ambulatory peritoneal dialysis (CAPD) patients. Method We performed a retrospective, longitudinal study, that included 60 PD patients followed at our unit. Demographic and clinical characteristics, such as age, gender, chronic kidney disease (CKD) etiology, time on PD program, dialytic efficacy (Kt/V), peritoneal equilibration test results, BIS results and episodes of peritonitis were registered from our unit database. We measured total sodium removal and estimated daily sodium intake using dietary recall for one day, during the assessment of dialysis adequacy. Based on a 2017 study of 87 patients on PD that sought a correlation between effective daily sodium intake (memory recollection) and urinary + peritoneal sodium sieving. It allowed, through logistic regression, the creation of equations for patients with and without renal residual function (RRF) (Pearson's 0.6). Statistical analyses were performed using SPSS statistics version 23.0. The statistical hypothesis tests with p-value &amp;lt;0.05 were considered significant. Results Sixty patients (male: 60%) with a mean age of 55,9 ± 9 years were selected. Mean time on dialysis was 24,8 months ± 11,9 (min. 2, max. 63). The most common etiology of CKD was glomerular diseases (n = 16, 26.7%), followed by uncertain etiology (n = 11, 18.3%) and diabetic kidney disease (n = 9, 15%). In total, 71,7% of patients were on continuous ambulatory peritoneal dialysis (CAPD). Mean Kt/V was 2,2 ± 0,6 and the majority of patients were high-average transporters. Previous comorbidities were arterial hypertension (n = 60, 100%), diabetes (n = 16, 26,7%), heart failure (n = 13, 21,7%), body mass index &amp;gt;30 kg/m2 (n = 22, 36,7%) and dyslipidemia (n = 40, 66,7%). According to European Society of Cardiology we define three stages of hypertension: stage 1 (140–159/90–99 mmHg) with 15 patients (25%), stage 2 (160–179/100–109 mmHg) with 14 patients (23,3%) and stage 3 (≥180/≥110 mmHg) with 4 patients (6,7%). In total, we have 27 patients (45%) with hypertension under control. A statistically significant positive correlation was found between a status of overhydration (≥2liters) with salt consumption (Na+ &amp;gt;2g) (p = 0,01) and also of hypertension stages 2 and 3 (p = 0,03). Conclusion In PD patients, BIS is a reliable method for evaluating volume status. We found that stable CAPD patients with uncontrolled BP had higher overhydration and salt consumption compared to patients whose BP was controlled. Control of hypervolemia and blood pressure is associated with better cardiac condition. Thus, it is important to encourage patients on peritoneal dialysis to significantly restrict salt intake.

Usefulness of Dietary Salt Restriction in Kidney Transplant Recipients: Analysis of Blood Pressure Levels Depending on the Differences in the Levels of Salt Intake

Sodium retention causes post-transplant hypertension, and sodium restriction is recommended in kidney transplantation recipients. We investigated the changes in salt intake and age-specific differences in salt intake over the post-transplant periods and considered what guidance is important for salt reduction tailored to individual recipients. We calculated salt intake for 38 recipients who underwent kidney transplantation from August 2013 to August 2018 using Tanaka's equation and extracted their blood pressure (BP) levels. The rate of achieving the desired level of salt intake (<6 g/d) was 7.9%. The average salt intake was 7.8 ± 1.4 g. Average BP by salt intake was as follows: <6 g/d, 109/71 mm Hg; 6 to <7 g/d, 127/84 mm Hg; 7 to <8 g/d, 124/79 mm Hg, 8 to <9 g/d, 130/73 mm Hg; 9 to <10 g/d, 133/83 mm Hg; and >10g/d, 137/81 mm Hg. Awareness of the need for salt restriction diminishes as time passes after transplantations, leading to increased salt uptake; therefore, regular guidance for keeping salt intake low is necessary for patients to maintain the awareness of salt restriction. The recipients with higher salt intake had higher blood pressure, suggesting the need for managing salt reduction. Dietary counseling showed a short-term efficacy for reducing sodium intake and clinically relevant BP improvement in renal allograft recipients.

Moderate dietary salt restriction improves blood pressure and mental well-being in patients with primary aldosteronism: The salt CONNtrol trial.

Primary aldosteronism (PA) is a frequent cause of hypertension. Aldosterone excess together with high dietary salt intake aggravates cardiovascular damage, despite guideline-recommended mineralocorticoid receptor antagonist (MRA) treatment. To investigate the antihypertensive impact of a moderate dietary salt restriction and associated physiological changes, including mental well-being. A total of 41 patients with PA on a stable antihypertensive regimen-including MRA-followed a dietary salt restriction for 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24-h urinary sodium excretion and nutrition protocols. Body composition was assessed by bioimpedance analysis and mental well-being by validated questionnaires. Dietary salt intake significantly decreased from 9.1 to 5.2g/d at the end of the study. In parallel, systolic (130 vs. 121mmHg) and diastolic blood pressure (BP) (84 vs. 81mmHg) improved significantly. Patients' aptitude of estimating dietary salt content was refined significantly (underestimation by 2.4 vs. 1.4g/d). Salt restriction entailed a significant weight loss of 1.4kg, improvement in pulse pressure (46 vs. 40mmHg) and normalization of depressive symptoms (PHQD scale, p<0.05). Salt restriction, cortisol after dexamethasone suppression test and dosage of renin-angiotensin-aldosterone-system (RAAS) blockers were independently associated with BP reduction. A moderate restriction of dietary salt intake in patients with PA substantially reduces BP and depressive symptoms. Moreover, the findings underline that a sufficient RAAS blockade seems to augment the effects of salt restriction on BP and cardiovascular risk.

Iodine Deficiency and Iodine Prophylaxis: An Overview and Update.

The thyroid gland requires iodine to synthesize thyroid hormones, and iodine deficiency results in the inadequate production of thyroxine and related thyroid, metabolic, developmental, and reproductive disorders. Iodine requirements are higher in infants, children, and during pregnancy and lactation than in adult men and non-pregnant women. Iodine is available in a wide range of foods and water and is susceptible to almost complete gastric and duodenal absorption as an iodide ion. A healthy diet usually provides a daily iodine consumption not exceeding 50% of the recommended intake. Iodine supplementation is usually necessary to prevent iodine deficiency disorders (IDDs), especially in endemic areas. The community-based strategy of iodine fortification in salt has eradicated IDDs, such as endemic goiter and cretinism, in countries providing adequate measures of iodine prophylaxis over several decades in the 20th century. Iodized salt is the cornerstone of iodine prophylaxis in endemic areas, and the continuous monitoring of community iodine intake and its related clinical outcomes is essential. Despite the relevant improvement in clinical outcomes, subclinical iodine deficiency persists even in Western Europe, especially among girls and women, being an issue in certain physiological conditions, such as pregnancy and lactation, and in people consuming unbalanced vegetable-based or salt-restricted diets. Detailed strategies to implement iodine intake (supplementation) could be considered for specific population groups when iodized salt alone is insufficient to provide adequate requirements.

Twenty-four-hour Urinary Salt Excretion on Admission Predicts Significant Weight Loss with Seven-day Dietary Salt Restriction in Hospitalized Patients with Chronic Kidney Disease: A Single-center Study.

In patients with chronic kidney disease (CKD), restricting dietary salt is recommended to prevent fluid retention. Rapid weight loss is often observed when CKD patients with a high salt intake are hospitalized and started on a low-salt diet. We investigated the effects of 7-day dietary salt restriction on weight loss in hospitalized patients with CKD. During the 7-day hospitalization, a low-salt (6 g/day) and low-protein (0.6-0.8 g/kg/day ideal body weight) diet was served to all patients. Urine samples were collected for the first 24 h after admission, and patients were divided into quartiles (Q1-Q4) by urinary salt excretion. Body weight was measured on days 1 and 7. Weight loss after admission was compared among the groups. Factors associated with weight loss were evaluated by multivariate logistic regression. The mean age of the patients was 70.3 ± 11.7 years, and 73% were male. Mean weight loss was 1.6 ± 1.7 kg on day 7. Weight loss was significantly greater in Q3 and Q4 than in Q1 (P = 0.009 and P <0.001, respectively). In the univariate analysis, weight loss correlated positively with 24-h urinary salt excretion on admission (γ2 = 0.146) and body mass index (γ2 = 0.223). The 24-h urinary salt excretion on admission and BMI were independently associated with weight loss of >2 kg. The adjusted odds ratios (95% confidence interval) were 1.24 (1.13-1.36) and 1.15 (1.07-1.22), respectively. Twenty-four-hour urinary salt excretion on admission is useful for predicting significant weight loss with short-term dietary salt restriction.

PS-BPP06-8: DIETARY SALT INTAKE PREDICTS FUTURE DEVELOPMENT OF METABOLIC SYNDROME IN THE GENERAL POPULATION

Objective: Dietary salt consumption is one of the most important modifiable factors in our lifestyle and restriction of dietary salt results in the reduction of blood pressure in previous studies. Excessive salt intake causes cardiovascular diseases independently of its effects on blood pressure. Since metabolic syndrome also increases a risk of cardiovascular disease, there may be some association between salt intake and metabolic syndrome. Therefore, we investigated a possible relationship between salt intake and future development of metabolic syndrome in the general population. Design and Methods: Consecutive 12,256 subjects without metabolic syndrome (male = 7,053, 52.1 ± 12.3 year-old) who visited our hospital for an annual physical check-up from April 2010 to March 2018 were enrolled. After baseline examination, subjects were followed up until March 2019 (median 1,582 days) with the endpoint being the development of metabolic syndrome. Metabolic syndrome was diagnosed according to the Japanese criteria (2005). Individual salt intake was estimated using a spot urine by a previously reported Tanaka method. Results: Salt intake was 8.7 ± 1.9 and 8.4 ± 1.8 g/day in male and female subjects, respectively, at baseline. During the follow-up period, 1,669 subjects developed metabolic syndrome (29.9 per 1,000 person-year) with the incidence being more frequent in male than female subjects (41.8 vs. 14.2 per 1,000 person-year). Non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the development of metabolic syndrome was 1.192 (1.164–1.221). Kaplan-Meier analysis where subjects were divided into gender-specific quartiles according to the baseline salt intake revealed that the incidence of metabolic syndrome were increased across the quartiles (19.5, 24.2, 33.1, and 43.9 per 1,000 person-years; logrank p &lt; 0.001). Multivariate Cox proportional hazard analysis adjusted for age, gender, body mass index, systolic blood pressure, heart rate, serum creatinine, uric acid, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, hemoglobin and current smoking habit at baseline revealed that salt intake predicted the new onset of metabolic syndrome (HR:1.055, 95%CI:1.028–1.082). Conclusions: Excessive salt intake is significantly associated with the new development of metabolic syndrome in the general population. The results suggest that salt restriction prevents cardiovascular diseases through the prevention of not only hypertension but also metabolic syndrome.

JS-NG-7: ASSOCIATION BETWEEN PLASMA ALDOSTERONE CONCENTRATION AND AMBULATORY BLOOD PRESSURE PROFILE IN PATIENTS WITH PRIMARY ALDOSTERONISM

Background: Primary aldosteronism (PA) is a major cause of curable hypertension with its morbidity rate 5–10% in hypertensive patients reported, and thus is highly prevalent in patients with hypertension, a cause of resistant hypertension, and closely associated with target organ damage compared with essential hypertension. Although an altered circadian blood pressure (BP) rhythm estimated by ambulatory blood pressure monitoring (ABPM) has been highlighted as a major contributor of CVD in essential hypertension, there would be very few reports investigating clinical significance of ABPM in PA patients. Therefore, we aimed to examine a possible association between plasma aldosterone concentration (PAC) and ABPM profile in PA patients. Methods: Consecutive 27 PA patients, who had been diagnosed by the functional tests and underwent adrenal venous sampling (AVS) from April 2015 to March 2020, were included in this study. All clinical indexes including 24-hour ABPM were measured during the hospitalization, and all participants received dietary salt restriction with 6 g/day of salt. The 24-hour ABPM was performed from the first day of hospitalization to the next day, and AVS was performed on the third day in the morning. Regarding PAC measurement, we collected blood samples during AVS. After resting for 30 minutes in a supine position, blood samples were collected from inferior vena cava by catheterization. During AVS, we also performed ACTH stimulation, and blood samples were collected essentially 1 hour after the stimulation. Results: We firstly analyzed a correlation between PAC and ABPM profile and found that PAC measured after ACTH stimulation (post-PAC) was negatively correlated with nocturnal dipping rate in both systolic and diastolic BPs (SBP and DBP) (R = -0.430, P = 0.025, and R = -0.431, P = 0.025, respectively), while PAC measured before ACTH stimulation (pre-PAC) was not. Thus, according to the median of post-PAC, we divided participants into lower PAC and higher PAC groups and compared clinical characteristics between the two groups. Compared to the lower PAC group, nocturnal SBP and DBP dipping rates and serum potassium levels were significantly decreased in the higher PAC group (SBP dipping 10.3 ± 6.4 vs 3.5 ± 7.7 %, P = 0.02; DBP dipping 13.6 ± 7.7 vs 5.5 ± 6.3 %, P = 0.01; serum potassium 4.1 ± 0.3 vs 3.7 ± 0.4 mEq/L, P = 0.03). Conclusions: In this cross-sectional study, higher PAC was significantly associated with a non-dipper circadian BP profile characterized by lower nocturnal BP dipping rates in PA patients. Prospective longitudinal study is warranted to seek for a causal relationship between hyperaldosteronism and ABPM profile.

PS-BPC08-10: IMPORTANCE OF DIETARY SALT RESTRICTION IN PRIMARY ALDOSTERONISM DURING TREATMENT WITH MINERALOCORTICOID RECEPTOR ANTAGONISTS: ROLE OF POSTTREATMENT PLASMA RENIN LEVELS

Objective: The purpose of this study is to measure the estimated dietary salt intake (eU-NaCl) when primary aldosteronism (PA) is treated with mineralocorticoid receptor antagonists (MRAs) and to evaluate whether it is important to reduce salt intake even while on MRA medications. Design and method: The eU-NaCl values were investigated in 26 PA patients who were treated with MRAs at pre-treatment and 6-month treatment. The eU-NaCl was calculated as follows: eU-NaCl (g/day) = 21.98 * {urinary sodium (mmol / L) / &lt;urinary creatinine (mg / dL) * 10&gt; * (Body Weight (kg) × 14.89 + Height (cm) × 16.14 - age × 2.043 - 2244.45)}. Results: Data are shown as median {first quartile - third quartile}. Various clinical parameters of 26 PA patients were compared between pre-treatment and 6 months MRA treatment; Systolic blood pressure (138 mmHg {124.5–157.7} vs 125 mmHg {117.8–130.8}, p &lt; 0.01) and diastolic blood pressure (86 mmHg {80.5–95.0} vs 78 mmHg {74.5–86.3}, p = 0.02) were decreased, serum potassium (3.9 mmol/L {3.8–4.3} vs 4.3 mmol/L {4.0–4.6}, p &lt; 0.01) and active renin concentration (ARC) (2.6 pg/mL {1.2–3.8} vs 6.1 pg/mL {3.5–10.3}, p &lt; 0.01) were increased significantly. The eU-NaCl (8.9 g/day {8.0–10.2} vs. 10.0 g/day {7.8–12.0}, p = 0.27) did not change. The correlation between the difference in eU-NaCl (ΔeU-NaCl) and the difference in ARC (ΔARC) before and after MRA treatment showed a significant inverse correlation (r = -0.418, p = 0.03). Furthermore, when the 26 patients were divided into 2 groups of ARC &gt;5 pg/mL and ARC &lt; 5 pg/mL after MRA treatment, ΔeU-NaCl and ΔARC showed no significant correlation in 16 patients with ARC ≧ 5 pg/mL (r = -0.481, p = 0.11), whereas a strong inverse correlation in 10 patients with ARC &lt; 5 pg/mL (r = -0.7599, p = 0.01). Conclusions: The present data indicate that post-MRA treatment ARC of less than 5pg/mL reflects insufficient improvement of salt sensitivity, suggesting the importance of dietary salt restriction even in the presence of MRA treatment.

TSPAN12 (Tetraspanin 12) Is a Novel Negative Regulator of Aldosterone Production in Adrenal Physiology and Aldosterone-Producing Adenomas.

Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a condition of low-renin hypertension, in which aldosterone overproduction is usually driven by a somatic activating mutation in an ion pump or channel. TSPAN12 is differentially expressed in different subgroups of APAs suggesting a role in APA pathophysiology. Our objective was to determine the function of TSPAN12 (tetraspanin 12) in adrenal physiology and pathophysiology. APA specimens, pig adrenals under dietary sodium modulation, and a human adrenocortical cell line HAC15 were used for functional characterization of TSPAN12 in vivo and in vitro. Gene ontology analysis of 21 APA transcriptomes dichotomized according to high versus low TSPAN12 transcript levels highlighted a function for TSPAN12 related to the renin-angiotensin system. TSPAN12 expression levels in a cohort of 30 APAs were inversely correlated with baseline plasma aldosterone concentrations (R=-0.47; P=0.009). In a pig model of renin-angiotensin system activation by dietary salt restriction, TSPAN12 mRNA levels and TSPAN12 immunostaining were markedly increased in the zona glomerulosa layer of the adrenal cortex. In vitro stimulation of human adrenocortical human adrenocortical cells with 10 nM angiotensin II for 6 hours caused a 1.6-fold±0.13 increase in TSPAN12 expression, which was ablated by 10 μM nifedipine (P=0.0097) or 30 μM W-7 (P=0.0022). Gene silencing of TSPAN12 in human adrenocortical cells demonstrated its inverse effect on aldosterone secretion under basal and angiotensin II stimulated conditions. Our findings show that TSPAN12 is a negative regulator of aldosterone production and could contribute to aldosterone overproduction in primary aldosteronism.