Sodium Restriction Research Articles

A Role for the Gastrointestinal Tract in Sodium Dysregulation Associated with the Salt Sensitive Phenotype in the Dahl S Rat

Introduction: Salt sensitive hypertension in the Dahl S rat (SS) has traditionally been attributed to elevated renal sodium reabsorption, largely mediated by the renal epithelial sodium channel (ENaC). Considering the role of ENaC in the distal colon epithelium in sodium absorption in the gastrointestinal tract, we hypothesized that the salt sensitive phenotype of SS rats may in part be attributable to increased absorption of sodium in the distal colon. Methods: Adult male SS and its control, the SR rats (12-14wo), were administered either low sodium diet (LS; 0.3% NaCl, Teklad) or moderately high sodium diet (HS; 2.0% NaCl, Teklad) ad libitum for two weeks. At endpoint, fecal samples were collected, dried for 72 hours at 70°C, weighed, and homogenized in deionized water. Fecal levels of sodium per gram of dry fecal weight were measured using flame photometry. Segments of distal colon wall were dissected and mounted in the Ussing chamber filled with warm, oxygenated Kreb’s solution containing D-glucose. Amiloride hydrochloride, a selective ENaC inhibitor, was applied to the tissue apical side in increasing concentrations (0-100μM) at 10-minute intervals. Total ionic currents (Isc, A) were measured under voltage clamp and presented as change from baseline. Results: We observed significantly lower fecal sodium levels in the SS compared to SR rats on LS diet (p<0.05), and a similar trend in fecal sodium levels between the SS and SR on HS diet (P=0.1). This was associated with significantly elevated amiloride-sensitive current in the distal colon of SS compared to the SR on LS and HS diets (p<0.01 and p<0.0001, respectively). Conclusion: Elevated amiloride-sensitive sodium current in the distal colon of SS rats is associated with decreased fecal sodium levels. This suggests increased sodium absorption in the SS rats and proposes a role for the gastrointestinal tract in sodium dysregulation associated with the salt sensitive phenotype in Dahl S rats. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex-specific role for the clock protein PER1 in renal ET-1 regulation in salt-sensitive hypertension

Global knockout (KO) of the clock protein PERIOD1 (PER1) in male, but not female, C57BL/6J mice displayed both blunted blood pressure and urinary endothelin-1 (ET-1) rhythms. More recently, we showed that Dahl salt-sensitive (SS) Per1 KO male rats had exacerbated SS hypertension, alongside increased renal injury, renal ET-1 gene ( Edn1) expression, and ET-1 peptide expression from kidneys collected during the rat’s inactive period (2 PM). Additionally, we see increased long non-coding RNA EDN1-AS, which has been suggested to modulate ET-1 production. However, it is unknown whether PER1 regulates rhythms of ET-1 in SS rats and whether PER1 regulates ET-1 in a sex-dependent way. The study objective was to test the hypothesis that PER1 negatively regulates renal EDN1-AS and Edn1 to modulate ET-1 in a sex- and time-dependent manner. To test this hypothesis, kidneys were collected during rat’s active period (2 AM) from male and female SS Per1 KO and SS control rats on a normal salt (0.4% NaCl) or 3 weeks high salt (4% NaCl) diet ( N=5-6). Renal ET-1 protein levels were measured by ELISA and semi- and quantitative PCR was performed to quantify the levels of EDN1-AS and Edn1. Renal ET-1 levels were significantly higher at 2 AM than our previously reported data at 2 PM in both SS Per1 KO and control male rats ( p<0.0001). Renal ET-1 levels were significantly increased in male SS Per1 KO rats following a high salt diet ( p=0.0362) but not in females ( p=0.9522). This was also reflected in the Edn1 mRNA levels (male, p=0.0005; female, p=0.0814). EDN1-AS levels were also increased in males ( p=0.0123) but not in females. Interestingly, significant sex differences were seen in EDN1-AS levels, where EDN1-AS levels were higher in males than females following both low and high salt diets, suggesting a potential novel sex-dependent mechanism for ET-1 regulation. Together, these data suggest sex-specific action of PER1 in the regulation of ET-1 in a model of salt-sensitive hypertension. Future work aims to investigate blood pressure and renal injury in female SS Per1 KO rats and whether this apparent negative regulation of ET-1 by PER1 contributes to the SS hypertensive and renal injury phenotype seen in male SS Per1 KO rats. This work was supported by the National Institutes of Health grants R35 HL135749 (to A.S.), R01 342 DK109570 (to M.G. and A.S.), and Department of Veteran Affairs grants I01 BX004024 (to A.S.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An Ex Vivo Approach to Studying Renin Dynamics

Hypertension is the leading risk factor for cardiovascular disease and impacts one in three adults globally. One non-coding mechanism that may affect blood pressure regulation and alter hypertension risk in the general population is the disruption of chromatin conformation. CCCTCF-binding factor (CTCF) has many important functions including regulating the conformation of chromatin by binding to specific DNA sequences. Renin has multiple CTCF motifs surrounding the gene and cellular expression of CTCF is critical for proper Renin expression. Using CRISPR-Cas9 in the Dahl salt-sensitive (SS) rat, we have developed three mutant rat models with one or more mutations to the CTCF motif surrounding the Renin gene. CTCF binding was confirmed to be disrupted in all three models at the CRISPR-targeted locations. Plasma renin activity (PRA) was measured in wild-type (WT) and mutant rats fed a 0.1%, 0.4% or 4.0% NaCl diet for four days. PRA in WT males responded as expected to dietary NaCl (17.52±0.81, 12.87±1.00, and 7.13±0.19 ng/mL; p<0.05 for 0.1% and 4.0% vs. 0.4%). Interestingly, two of our male mutant models failed to increase their PRA on the 0.1% NaCl diet (CTCF1=13.87±0.86; CTCF2=13.95±0.59; p<0.05 compared to WT 0.1% NaCl). Despite this, no differences in Renin mRNA were detected. We hypothesize Renin transcriptional response to salt depletion is delayed in the mutant models compared to WT. To test this, we developed an ex vivo approach to culture kidney slices and evaluate Renin expression to a variety of stimuli. Kidneys from SS rats fed low salt (LS; 0.4% NaCl) or high salt (HS) diet (4.0% NaCl) for 24 hours were harvested, sliced, and cultured in basal media or media containing increasing salt. Renin expression was examined at 1, 2, 4, 8 and 24 hrs of incubation. Kidney slices from SS rats fed HS that were incubated basal media stimulated Renin expression as soon as 2 hrs and continued to increase until 8 hrs. This was the first time for establishing an ex vivo approach for motoring the dynamic changes in Renin expression in response to a stimulus by culturing kidney slices. This method could be used to evaluate other stimuli, such as therapeutics, and could decrease the number of animals needed for a study. Funded by NIH 1HL149620. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Salt-Sensitive Hypertension and Renal Damage are Amplified by Adoptive Transfer of CD4+ and Not CD8+ T Cells: A Role of NADPH Oxidase 2 (NOX2)

Infiltration of T cells into the kidney of the Dahl Salt Sensitive (SS) rat model of human disease accompanies the development of salt-sensitive hypertension and renal damage. Deletion of T cells on the Dahl SS genetic background (SSCD247−/−) attenuates hypertension and renal damage, and subsequent replacement of T cells by splenocyte transfer restores the disease phenotype. The present studies were performed to assess if the T cell subtype (CD4+ vs CD8+) is important in Dahl SS hypertension and interrogate the mechanism of action. In initial experiments, adoptive transfer of purified CD4+ or CD8+ T cells (~5 million) from splenocytes isolated from the Dahl SS (CD4+ SS→CD247 or CD8+ SS→CD247) or PBS vehicle (PBS→CD247) into the SSCD247−/− rat was performed on postnatal day 5. Animals were recovered and instrumented with radiotelemeters at 7 weeks of age. After a week of recovery, baseline measurements of blood pressure and albumin excretion were obtained while rats were fed a low salt (LS, 0.4% NaCl) diet. Rats were then switched to a high salt (HS, 4.0% NaCl) diet for 21 days, with continuous blood pressure measurements and urine collections every 7 days. On day 21, the rats were euthanized, and their kidneys were perfused and collected for immune cell analysis by flow cytometry. During the LS baseline period there was no significant difference observed in mean arterial pressure (MAP) between the CD4+ SS→CD247, CD8+ SS→CD247, or PBS→CD247 groups (113±1, 115±1, 114±1 mmHg; n=21, 10, 24, respectively). After three weeks of HS, rats receiving CD4+ T cells from the SS (CD4+ SS→CD247) demonstrated an amplified salt-sensitive hypertension (154±3 mmHg) and albuminuria (184±22 mg/day) compared to blood pressure (140±3 and 145±3 mmHg) and albuminuria (82±9 and 85±8 mg/day) in the CD8+ SS→CD247 or PBS→CD247 groups, respectively. Since the deletion of the p67phox subunit of NADPH oxidase 2 (NOX2) in adoptively transferred splenocytes attenuated Dahl SS hypertension and kidney damage, parallel studies examined the influence of deletion of p67phox in CD4+ (n=14) and CD8+ T cells (n=8). The adoptive transfer of either CD4+ or CD8+ T cells lacking functional NOX2 did not alter the LS or HS blood pressure or albuminuria when compared to the PBS control group. Finally, a flow cytometric analysis at the end of the experiment confirmed the absence of CD3+ T cells in the PBS→CD247 and documented the reconstitution of equal numbers of CD4+ cells in the blood and kidney of the rats receiving CD4+ cells with intact or deficient NOX2. Interestingly, no difference was observed in CD8+ T cells in the kidney and blood of rats receiving CD8+ cells with intact or deficient NOX2, but a significant number of CD4+ T cells were also observed in the SSCD247−/− rats receiving the purified CD8+ T cells. In summary, these studies demonstrate that CD4+ T cells amplify salt-sensitive hypertension and renal damage in the Dahl SS via a NOX2-dependent mechanism while CD8+ T cells do not alter disease phenotypes when compared to PBS control. GRANTS: HL161231, HL166458, Georgia Research Alliance. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lactobacillus plantarum 299v administration prevents high-sodium diet-induced glycocalyx degradation and arterial dysfunction

A central feature of cardiovascular disease (CVD) is arterial dysfunction (i.e., elevated systolic blood pressure [BP], aortic stiffening, and endothelial dysfunction), which may be initiated by a degraded endothelial glycocalyx. The glycocalyx is a negatively charged structure bound to the vascular endothelium that appears to play a critical role in cardiovascular health, particularly by buffering sodium in blood, although excessive sodium degrades the glycocalyx. In the United States, a high-sodium (HS) diet is consumed by ~90% of the population with average sodium intake ~2.3x greater than recommended by the American Heart Association. We have previously shown that HS diet induces glycocalyx degradation and arterial dysfunction in outbred, genetically diverse UM-HET3 mice. Others have shown that HS diet lowers Lactobacillus abundance in mouse gut microbiome. However, it is unknown whether maintaining Lactobacillus would prevent HS diet-induced glycocalyx degradation and arterial dysfunction. To test this concept, male and female UM-HET3 mice (n=21-35/group) were randomized into a low-sodium (LS) diet (1% NaCl), HS diet (4% NaCl), or HS diet with Lactobacillus plantarum 299v (Lp299v) administration (60 million CFU/ml in drinking water) for 12 weeks. Glycocalyx barrier function was determined by assessing perfused boundary region (PBR), which represents red blood cell penetration into the glycocalyx. At week 12, we observed higher PBR in HS mice (2.36±0.04 μm) compared to LS and HS+Lp299v mice (2.09±0.03 and 2.20±0.04 μm, respectively; p<0.05), indicating a worse glycocalyx barrier function in HS mice. PBR was similar between LS and HS+Lp299v mice (P>0.05), indicating a preserved glycocalyx barrier function in HS+Lp299v mice. Systolic BP was higher in HS (127±1 mmHg) compared to LS and HS+Lp299v mice (113±1 and 118±1 mmHg, respectively; p<0.05). Aortic stiffness, determined by aortic pulse wave velocity (PWV), was also higher in HS (345±5 cm/s) compared to LS and HS+Lp299v mice (268±5 and 300±3 cm/s, respectively; p<0.05). However, systolic BP and aortic PWV were higher in HS+Lp299v compared to LS mice (p<0.05). Ex vivo endothelial function, determined by the maximal vasodilatory response to acetylcholine in the carotid artery, was lower in HS (83.9±1.3%) compared to LS and HS+Lp299v mice (89.8±1.3 and 90.1±1.0%, respectively; p<0.05). Endothelial function was similar between LS and HS+Lp299v mice (P>0.05). In summary, Lp299v administration prevents HS diet-induced glycocalyx degradation and endothelial dysfunction, while mitigating HS diet-induced elevations in systolic BP and aortic stiffness. These findings suggest that Lp299v administration may be a novel strategy to lower the risk of CVD in humans that consume a HS diet. This study was funded in part by a grant from the National Institutes of Health (R00 AT010017). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sodium Loading Does Not Induce Oxidative Stress-Mediated Reductions in Vascular Function in Young Adults

Short-term, high sodium diets decrease dilation responses in conduit arteries and the microvasculature when compared to low sodium diets (e.g., 7000 vs. 500 mg/day). Supraphysiological antioxidant treatment mitigates these effects supporting a role for oxidative stress in sodium-induced vascular impairments. It is unclear whether these effects are present when high sodium conditions are compared to the sodium level of a typical American diet (~3400 mg/day). Therefore, we tested the hypotheses that sodium added to the habitual diet of young adults would reduce flow mediated dilation (FMD) and post-ischemic reactive hyperemia (RH) and that an acute infusion of the antioxidant ascorbic acid (AA) would attenuate the vascular consequences of excess sodium. Methods: Young adults (6M / 8F; age: 26 ± 4 y; BMI: 23.6 ± 2.5 kg/m2) were studied following 10 days of sodium loading (SL) via table salt-filled capsules (3900 mg sodium/day) and 10 days of placebo capsules in addition to their normal diet, in random order. Total sodium intake was estimated via 24-hour urinary sodium content on day 10. On day 11, brachial artery diameter and blood velocity were continuously measured via duplex ultrasound at baseline and after 5 min of forearm ischemia. FMD, the post-ischemic change in brachial artery diameter relative to baseline diameter, provided an index of conduit artery endothelial function. The total RH in the 2 min following ischemia was measured for an index of microvascular function. Within each condition, testing was performed before (pre-AA) and after (post-AA) a 20 min intravenous infusion of 0.06 g of AA/kg lean body mass. Results: Urinary sodium content was increased by SL compared to the placebo (285 ± 94 vs. 160 ± 75 mmol/24 h, p<0.001) indicating approximate sodium intakes of 6600 and 3700 mg/day, respectively. Mean arterial pressure did not differ across conditions pre-AA (SL: 77 ± 7; placebo: 75 ± 5 mmHg, P=0.40) or post-AA (SL: 79 ± 8; placebo: 76 ± 5 mmHg, P=0.17). Brachial artery FMD was not different across time or condition (SL pre-AA: 8.7 ± 3.6, post-AA: 8.8 ± 4.2% vs. placebo pre-AA: 8.8 ± 3.2, post-AA: 8.1 ± 3.5%, time x condition interaction P=0.48). RH was similar following SL and placebo (condition effect: P=0.38) but was reduced in both conditions post AA (SL: Δ-45 ± 44 ml, P=0.01; placebo: Δ-72 ± 59ml, p<0.001). Conclusion: Contrary to our hypothesis, 10 days of sodium loading did not decrease FMD or post- ischemic RH in young adults compared to their habitual diet. Likewise, acute antioxidant treatment did not augment FMD in either condition and paradoxically decreased total RH independent of sodium intake. These data suggest that a short-term increase in dietary sodium intake in healthy young adults does not elicit oxidative stress-induced reductions in vascular function. NIH 5R01HL104106 and 5P20GM113125; AHA 20POST35080171. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Potassium Supplementation Offsets the Effects of a High Sodium Diet on Endothelial Function but Not Blood Pressure Reactivity in Healthy, Normotensive Adults

High sodium diets are linked to endothelial dysfunction and increased blood pressure reactivity (BPR) to physiological stimuli, which are both notable cardiovascular disease (CVD) risk factors. High potassium diets are shown to lower blood pressure (BP) and improve endothelial function; however, previous interventions often increased potassium intake using food, making it diffcult to attribute these effects to potassium alone. The interactive effects of sodium and potassium on pre-clinical CVD risk factors remains unclear. The objective of this study was to determine if potassium can independently counteract the effects of a high sodium diet on endothelial function and BPR in healthy, normotensive adults. We hypothesized that endothelial function and BPR would be impaired with a high sodium diet compared to a low sodium diet but would improve with the addition of potassium supplements. Nineteen participants (13W/6M, age 26±4 y, BP 108±11/71±9 mmHg, BMI 25.1±2.7 kg/m2) completed three 10-day controlled diets in random order: a moderate potassium/low sodium (MK/LS; 55 mmol K/50 mmol Na) diet, a moderate potassium/high sodium (MK/HS; 55 mmol K/300 mmol Na) diet, and a high potassium/high sodium (HK/HS; 120 mmol K/300 mmol Na) diet. Potassium intake was increased using potassium chloride supplements. Dietary compliance was confirmed by urinalysis. On day 10, endothelial function was assessed by brachial artery flow-mediated dilation (FMD), and BPR was assessed by measuring ΔMAP in response to an isometric handgrip exercise (IHG) with post-exercise ischemia (PEI) and the cold pressor test (CPT). Differences across diets were assessed by repeated-measures ANOVA. Twenty-four-hour ambulatory mean arterial pressure (MAP), which was measured on day 9, was not different across diets (MK/LS: 81±5 mmHg; MK/HS: 79±4 mmHg; HK/HS: 80±6 mmHg; p=0.15), indicating our participants were salt-resistant. FMD was significantly lower on the MK/HS diet compared to the MK/LS diet (MK/HS: 5.8±2.8% vs. MK/LS: 8.2±3.7%; p=0.004) and was rescued with the addition of potassium supplements (HK/HS: 8.9±3.2; p=0.009 compared to MK/HS). FMD on MK/LS and HK/HS diets were similar (p>0.05). There were no differences across diets in ΔMAP in response to the IHG (p=0.73), the PEI (p=0.67), or the CPT (p=0.94). Our findings suggest that, while sodium and potassium may not affect BPR, potassium supplementation effectively counteracts sodium-induced endothelial dysfunction in healthy, normotensive, salt-resistant adults. AHA/VIVA 23POST1009835; NHLBI R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic Kidney Disease Risk Awareness, Dietary Intake, and Food Security Among Black Male College Students

ObjectivesNutrition, lifestyle factors, and awareness of chronic kidney disease (CKD) risk are vital tools for preventing or delaying its development and progression in Black American (BA) males. Few published studies assess awareness of CKD risk in BA male college students despite being at high risk. This study aimed to 1) assess the awareness of CKD risk among BA male college students and 2) identify dietary and lifestyle habits related to CKD risk. MethodsThis was a cross-sectional online survey utilizing a network sampling technique. Inclusion criteria were self-identification as a Black American male and current enrollment in a university. Participants were recruited through publicly available social media sites and emails. The online questionnaire contained demographic, health status, and food security items. Pearson’s correlations explored associations between continuous variables; independent samples t-tests compared mean scores of responses between perceived risk of disease groups. ResultsSixty-seven participants completed the survey. Only 22.4% perceived they were at increased risk for kidney disease, while 49.3% felt at increased risk for developing hypertension (HTN). More respondents (32.8%) also felt at increased risk for developing diabetes than kidney disease. Dietary sodium restriction was reported by 34.3%, while only 14.9% had been advised to do so by a healthcare provider. Half of the respondents were deemed food insecure, and 17.86% were categorized as experiencing very low food security. ConclusionAwareness of CKD risk is low for BA male college students and lags behind awareness of HTN and diabetes risk. There may be a lack of knowledge regarding CKD as a long-term complication of HTN and diabetes. Dietary sodium restriction is marginal, and food security is a significant challenge in this high-risk group. Educational initiatives are needed to increase awareness of CKD risk among BA male college students.

Is dietary sodium restriction superior to regular diet in hospitalized patients with heart failure to decrease length of stay?

Is dietary sodium restriction superior to regular diet in hospitalized patients with heart failure to decrease length of stay?

Thyroid function and iodine intake: global recommendations and relevant dietary trends.

Iodine is a micronutrient that is essential for thyroid hormone production. Adequate iodine intake is especially important during pregnancy and early life, when brain development is dependent on thyroid hormones. Iodine intake recommendations vary around the world, but most recommendations generally reflect the increased requirements during pregnancy and lactation, although adequate iodine intake before pregnancy is also important. Tremendous progress has been made in improving iodine intake across the world over the past 30 years, mainly through salt-iodization programmes. However, in countries without strong iodine fortification programmes, and with shifts in dietary patterns, a need has arisen for health organizations, governments and clinicians to ensure that adequate iodine is consumed by everyone in the population. For example, in countries in which adequate iodine intake depends on individual food choice, particularly of iodine-rich milk and dairy products, intake can be highly variable and is also vulnerable to changing dietary patterns. In this Review, iodine is considered in the wider context of the increasing prevalence of overweight and obesity, the dietary trends for salt restriction for cardiovascular health and the increasing uptake of plant-based diets.

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.

Restricted Daily Sodium Intake as Heart Failure Management: A Systematic Review

Objective: To evaluate mortality and morbidity in HF patients receiving sodium restriction. Study Design: Systematic Literature Review (SLR) of RCTs and Cohort studies worldwide published between Jan 2013 to Jan 2023. Methodology: We systematically selected RCTs and Cohort studies with sodium restriction as an intervention published within the last decade from five databases (PubMed, Scopus, Cochrane Library, Embase, and Medline). The full texts retrieved were assessed for risk of bias, and then a systematic review was performed. The endpoints analyzed were mortality and morbidity. Result: Five RCTs and two cohort studies were included in this study, with 2,505 participants. The endpoints retrieved were mortality and morbidity (hospitalization, NYHA functional class, BNP or NT-proBNP level, quality of life, and congestion). No improvement was seen in mortality and hospitalization, but sodium restriction improved the rest of the morbidity indicators. Over-restricted and overconsumption of sodium intake might worsen HF presentation. When analyzed based on the HF groups, there was not enough evidence to recommend sodium dose based on ejection fraction; however, there was potentially more benefit for patients with higher NYHA classes. However, more evidence is still needed. Conclusion: Sodium restriction did not benefit mortality and hospitalization but improved quality of life, systolic blood pressure, and BNP or NT-pro BNP levels in all HF classes.

An educational intervention for improving knowledge, attitude, and practice of dietary salt intake among individuals with hypertension in public sector secondary care facilities, Agra, India, 2021.

We conducted a pre-post intervention study to determine knowledge, attitude, and practice toward dietary salt intake before, immediately, and 1-month after nurse-led one-on-one counseling. We purposively selected three public health facilities in Agra, India, and enrolled all eligible hypertensive patients aged 18-60 under treatment for ≥6 months. Of the 153 patients at the 1-month follow-up, counseling improved knowledge (4%vs. 42%, p<.001), a greater prioritization of a low salt diet (34%vs. 52%, p<.001), and practice of adding less salt to the dough (48% to 41%, p<.001). The counseling intervention improved knowledge, attitude, and practice toward dietary salt intake.

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.

Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation.

Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.

Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure. Dahl salt-sensitive rat model was used for chronic, continuous observation of blood pressure. Rats were fed a high salt diet to induce hypertension, and then the diet was switched back to normal sodium content. We found that developed hypertension was irreversible by salt cessation: after a short period of reduction, blood pressure grew even higher than in the high-salt phase. Notably, the self-sustaining phase of hypertension was sensitive to benzamil treatment due to sustaining epithelial sodium channel hyperactivity, as shown with patch-clamp analysis. Glomerular damage and proteinuria were also irreversible. In contrast, some mechanisms, contributing to the development of salt-sensitive hypertension, normalized after salt restriction. Thus, flow cytometry demonstrated that dietary salt reduction in hypertensive animals decreased the number of total CD45+, CD3+CD4+, and CD3+CD8+ cells in renal tissues. Also, we found tubular recovery and improvement of glomerular filtration rate in the postsalt period versus a high-salt diet. Based on earlier publications and current data, poor response to salt restriction is due to the differential contribution of the factors recognized in the developmental phase of hypertension. We suggest that proteinuria or electrolyte transport can be prioritized over therapeutic targets of inflammatory response.

Effect of Low-Level Tragus Stimulation on Cardiac Metabolism in Heart Failure with Preserved Ejection Fraction: A Transcriptomics-Based Analysis.

Abnormal cardiac metabolism precedes and contributes to structural changes in heart failure. Low-level tragus stimulation (LLTS) can attenuate structural remodeling in heart failure with preserved ejection fraction (HFpEF). The role of LLTS on cardiac metabolism is not known. Dahl salt-sensitive rats of 7 weeks of age were randomized into three groups: low salt (0.3% NaCl) diet (control group; n = 6), high salt diet (8% NaCl) with either LLTS (active group; n = 8), or sham stimulation (sham group; n = 5). Both active and sham groups received the high salt diet for 10 weeks with active LLTS or sham stimulation (20 Hz, 2 mA, 0.2 ms) for 30 min daily for the last 4 weeks. At the endpoint, left ventricular tissue was used for RNA sequencing and transcriptomic analysis. The Ingenuity Pathway Analysis tool (IPA) was used to identify canonical metabolic pathways and upstream regulators. Principal component analysis demonstrated overlapping expression of important metabolic genes between the LLTS, and control groups compared to the sham group. Canonical metabolic pathway analysis showed downregulation of the oxidative phosphorylation (Z-score: -4.707, control vs. sham) in HFpEF and LLTS improved the oxidative phosphorylation (Z-score = -2.309, active vs. sham). HFpEF was associated with the abnormalities of metabolic upstream regulators, including PPARGC1α, insulin receptor signaling, PPARα, PPARδ, PPARGC1β, the fatty acid transporter SLC27A2, and lysine-specific demethylase 5A (KDM5A). LLTS attenuated abnormal insulin receptor and KDM5A signaling. HFpEF is associated with abnormal cardiac metabolism. LLTS, by modulating the functioning of crucial upstream regulators, improves cardiac metabolism and mitochondrial oxidative phosphorylation.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.

Edukasi Diet Rendah Garam dan Pembatasan Cairan terhadap Self Efficacy dan Motivasi untuk Sembuh pada Pasien Hemodialysis

This study aims to determine low salt diet education and fluid restriction on self-efficacy in controlling fluid salt intake and motivation to recover in haemodialysis patients. The method used in this research is quasi-experimental research. This quasi-experimental uses a Non Equivalent Control Group design or often called Non Randomised Control Group Pretest And Posttest Design. The results showed that based on the results of the Dependent T Test there was a difference in Self Efficacy before and after education in the intervention group with a p-value of 0.001 &lt;0.05 with a t value of 4.661 there was a difference in motivation to recover before and after education in the intervention group with a p-value of 0.001 &lt;0.05 with a t value of 4.001. The conclusion of this study is that low salt diet education and fluid restriction have an effect on Self Efficacy and motivation to recover in haemodialysis patients. Keywords: Education, Haemodialysis, Self Efficacy, Motivation