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Objective: Current international guidelines recommend home blood pressure (BP) measurement and low sodium and high potassium intakes for the management of hypertension. We hypothesized that increased home BP measurement may result in more effective management of sodium and potassium intakes and BP., Methods: We examined associations of home BP measurement days with changes in the urinary sodium-to-potassium (Na/K) ratio, estimated salt and potassium intakes and BP. We included 209 healthy participants (mean age, 55.9 years; 56.5% women) from a prospective cohort study. We examined 1-year data on self-measured home BP and spot urine samples., Results: Median (interquartile range) days of home BP measurement was 324 (225-358) over 1-year. Baseline mean (SD) Na/K ratio, salt and potassium intakes, morning and evening SBP, and morning and evening DBP were 3.8 (2.3), 8.5 (1.9) g/day, 1833.5 (416.5) mg/day, 120.4 (14.0) mmHg, 118.2 (14.2) mmHg, 79.2 (10.1) mmHg, and 76.2 (10.1) mmHg, respectively. In multivariable-adjusted linear regression , β (standard error) per 10 days increase in number of home BP measurement were -0.031 (0.017) for Na/K ratio, -0.036 (0.015) for salt intake, -1.357 (2.797) for potassium intake, -0.178 (0.064) for morning SBP, -0.079 (0.041) for morning DBP, -0.109 (0.067) for evening SBP and -0.099 (0.045) for evening DBP. Additionally, relationships persisted for men and women, but changes in salt intake were more pronounced among participants taking antihypertensive medication (interaction P = 0.002)., Conclusion: Continuous measurement of home BP may lead not only to self-monitoring of BP, but also to declines in salt intakes and some BP indices., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The spectrum of diseases with overactive renin-angiotensin-aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography-mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m 2 . In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (β: 0.0027; p = 4.2 × 10 -7 ). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (β: 0.0022; p = 2.1 × 10 -5 ). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion., (© 2022. The Author(s).)

Salt intake is often estimated by the amount of sodium excreted in urine, and miso has been reported to increase it. This cross-sectional study investigated the relationship between obesity and high estimated salt intake with and without habitual miso consumption. Estimates of salt intake (g/day) were calculated using urinary sodium excretion, and a high estimated intake was defined as greater than the median amount of 9.5 g/day. Participants were divided into four groups based on estimated salt intake and miso consumption. Among 300 people, the proportions of obesity were 77.8% ( n = 14/18), 40.2% ( n = 53/132), 26.0% ( n = 33/127), and 34.8% ( n = 8/23) in the (+/-), (+/+), (-/+), and (-/-) groups of high estimated salt intake/habitual miso consumption, respectively. Compared with the (+/-) group, the adjusted odds ratios for obesity were 0.07 (95% confidence interval (CI): 0.02-0.26, p < 0.001), 0.16 (95% CI: 0.03-0.76, p = 0.022), and 0.14 (95% CI: 0.04-0.51, p = 0.003) in the (-/+), (-/-), and (+/+) groups, respectively. The presence of obesity was not much higher in people with high estimated salt intake with habitual miso consumption than that in people without. Clinicians should be aware that miso consumption promotes salt excretion, which may lead to an apparently higher estimated salt intake than actual.

Ethnopharmacological Relevance: Lagopsis supina (Steph.) Ik. -Gal. ex Knorr. has been widely used as a remedy treatment for diuresis and edema in China over 2500 years. Our previous results showed that the aqueous soluble fraction from L. supina (LSB) possessed acute diuretic effect., Aim of the Study: The aim of this study was to appraise the acute (6 h) and prolonged (7 d) diuretic effects, underlying mechanisms, and chemical profiling of LSB., Materials and Methods: The chemical profiling of LSB was performed by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS/MS). Then, oral administration of LSB (40, 80, 160 and 320 mg/kg) and furosemide (10 mg/kg) once daily for 7 consecutive days to evaluate the diuretic effects in saline-loaded rats. The body weight, food consumption, and water intake were recorded once daily. The urinary volume, pH and electrolyte concentrations (Na + , K + , Cl - , and Ca 2+ ) were measured after administration drugs for acute and prolonged diuretic effects. In addition, the serum levels of Na + -K + -ATPase, angiotensin II (Ang II), anti-diuretic hormone (ADH), aldosterone (ALD), atriopeptin (ANP), aquaporins (AQPs)-1, 2 and 3 were determined by ELISA kits. The mRNA expressions and protein levels of AQPs-1, 2 and 3 were analyzed by real-time quantitative PCR and Western blot assays, respectively., Results: 30 compounds were identified in LSB based on accurate mass and MS/MS fragmentation compared to literature, among which phenylpropanoids and flavonoids could be partly responsible for the major diuretic effect. Daily administration of LSB (160 or 320 mg/kg) prominently increased urinary excretion volume after the 2 h at the first day of treatment, remaining until the 7th day. LSB did not cause Na + and K + electrolyte abnormalities, and has minor effect on Cl - and Ca 2+ concentrations at 320 mg/kg. Furthermore, LSB observably suppressed renin-angiotensin-aldosterone system (RAAS) activation, including decreased serum levels of Ang II, ADH, and ALD, and prominently increased serum level of ANP in rats. LSB treatment significantly down-regulated the serum levels, mRNA expressions and protein levels of AQP1, AQP2, and AQP3., Conclusion: LSB has a prominent acute and prolonged diuretic effects via suppression of AQP and RAAS pathways in saline-loaded rats, and support the traditional folk use of this plant. Taken together, LSB might be a potential diuretic agent., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Blood Pressure (BP) control is largely unsatisfied in End Stage Kidney Disease (ESKD) principally due to sodium retention. Peritoneal Dialysis (PD) is the most common type of home dialysis, using a peritoneal membrane to remove sodium, though sodium removal remains challenging., Methods: This is a case-study reporting two consecutive ESKD patients treated by a novel peritoneal PD solution with a mildly reduced sodium content (130 mmol/L) to treat hypertension., Results: In the first case, a 78-year-old woman treated by Continuous Ambulatory PD (CAPD) with standard solution (three 4 h-dwells per day 1.36% glucose 132 mmol/L) showed resistant hypertension confirmed by ambulatory blood pressure monitoring (ABPM), reporting 24 h-BP: 152/81 mmHg, day-BP:151/83 mmHg and night-ABP: 153/75 mmHg, with inversion of the circadian systolic BP rhythm (1.01), despite use of three anti-hypertensives and a diuretic at adequate doses. No sign of hypervolemia was evident. We then switched from standard PD to low-sodium solution in all daily dwells. A six-months low-sodium CAPD enabled us to reduce diurnal (134/75 mmHg) and nocturnal BP (122/67 mmHg), restoring the circadian BP rhythm, with no change in ultrafiltration or residual diuresis. Diet and drug prescription were unmodified too. The second case was a 61-year-old woman in standard CAPD (three 5 h-dwells per day) suffering from hypertension confirmed by ABPM (mean 24 h-ABP: 139/84 mmHg; mean day-ABP:144/88 mmHg and mean night-ABP:124/70 mmHg). She was switched from 132-Na CAPD to 130-Na CAPD, not changing dialysis schedule. No fluid expansion was evident. During low-sodium CAPD, antihypertensive therapy (amlodipine 10 mg and Olmesartan 20 mg) has been reduced until complete suspension. After 6 months, we repeated ABPM showing a substantial reduction in mean 24 h-ABP (117/69 mmHg), mean diurnal ABP (119/75 mmHg) and mean nocturnal ABP (111/70 mmHg). Ultrafiltration and residual diuresis remained unmodified. No side effects were reported in either cases., Conclusions: This case-report study suggests that mild low-sodium CAPD might reduce BP in hypertensive ESKD patients.

The hormone aldosterone is essential for maintaining K + and Na + balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K + diet. Many of these changes were not detectable by analyzing whole kidney samples from the same animals. When comparing responses to high-K + versus low-Na + diets, protein translation, chaperone-mediated protein folding, and protein ubiquitylation were likely to be significantly altered in the DCT subsequent to a high-K + diet. In conclusion, this study defines an in vivo protein landscape of the DCT in male mice following either a low-NaCl or a high-K + diet and acts as an essential resource for the kidney research community. NEW & NOTEWORTHY The mineralocorticoid aldosterone, essential for maintaining body K + and Na + balance, has different effects if secreted due to hypovolemia or hyperkalemia. Here, we used proteomics to profile kidney distal convoluted tubule (DCT) cells isolated by a novel FACS approach from mice fed a low-Na + diet (mimicking hypovolemia) or a high-K + diet (mimicking hyperkalemia). The study provides the first in-depth proteome of the mouse DCT and insights into how it is physiologically regulated.

Arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) are polyunsaturated fatty acids (FA) naturally present in breast milk and added to most North American infant formulas (IF). We investigated the safety and efficacy of novel sodium and potassium salts of arachidonic acid as bioequivalent to support tissue levels of ARA comparable to the parent oil; M. alpina oil (Na-ARA and K-ARA) and including a Na-DHA group. Pigs of both sexes were randomized to one of five dietary treatments ( n = 16 per treatment; 8 male and 8 female) from postnatal day 2 to 23. ARA and DHA were included as either triglyceride (TG) or salt. Target dietary ARA/DHA concentrations as percent of total FA by weight were as follows: TT (0.47 TG/0.32 TG), NaT (0.47 Na-salt/0.32 TG), KT (0.47 K-salt/0.32 TG), and Na0 (0.47 Na-salt/0.00), NaNa (0.47 Na-salt/0.32 Na-salt). The primary outcome in this study was bioequivalence of ARA brain accretion. Growth performance; blood and tissue fatty acid levels; liver histology; complete blood cell counts; and serum chemistries were all evaluated. Overall, diets containing test sources of ARA and DHA did not affect growth performance; liver histology; or substantially influence hematological outcomes as compared with TT. The results confirm that the use of Na and K salt forms of ARA yield bioequivalent ARA accretion in the cerebral cortex and retinal tissue compared to TG-ARA. These findings confirm that use of Na-ARA and K-ARA salts in the young pig was safe and nutritionally bioequivalent to TG-ARA for critical neural tissues.

Background: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa., Methods: We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method., Results: Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI) -1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (β = 1.16, 95% CI 1.06-1.27; P < 0.0001)., Conclusions: A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Rationale: Pituitary tumor apoplexy (PTA) is a rare clinical syndrome which requires urgent diagnosis and treatment due to its life-threatening consequences. Management of undiagnosed pituitary tumor before pregnancy is a problem during pregnancy., Patient Concerns: We reported a case with PTA which was not diagnosed before pregnancy presenting with vomiting associated with hyponatremia during the third trimester. After supplying the sodium the patient presented with dysarthria and hemiplegia., Diagnoses: MRI examination showed PTA accompanied with extrapontine myelinolysis (EPM)., Interventions: The patient was given hydrocortisone according to the symptoms gradually to taper off dose, at the same times oral levothyroxine therapy (25μg/day) was given., Outcomes: The patient delivered a healthy baby via cesarean section at hospital at 38 + 1 week of gestation. We performed MRI examination regularly and the tumor regressed significantly 8 months postpartum., Lessons: We reported a case as PTA associated with EPM. Headache during pregnancy is often nonspecific, so careful medical history inquiry is very important., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Functional variants in genes of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems have already been implicated in blood pressure (BP) modulation, but few studies have focused on a nutrigenetics approach. Thus, the aim of this study is to verify the effects of the interaction between genetic polymorphisms (rs4340-ACE, rs699-AGT, and rs1799722-BDKRB2) and micronutrient consumption (sodium, potassium, calcium, and magnesium) on BP values of normotensive adult individuals. The study included 335 adults, men and women, 25.5 (6.6) years old. Biochemical, anthropometric, BP measurements, and food intake data were assessed for all participants. Gene-nutrient interaction on BP outcome was tested by multiple linear regression with manual backward stepwise modeling. Our results indicated that individuals with G allele for rs699 polymorphism, in the increase of sodium and magnesium consumption, both in the genotypic model (sodium, p = 0.035; magnesium, p = 0.016) and in the dominant model (sodium, p = 0.009; magnesium, p = 0.006) had higher systolic BP (SBP) levels compared to AA homozygotes (sodium, p = 0.001; magnesium, p < 0.001). Also, individuals with the T allele for the rs1799722 polymorphism, with higher calcium intake, had significantly higher levels of SBP and diastolic BP (DBP) when compared to CC homozygotes (p = 0.037). In conclusion, our findings pointed for significant interactions between genetic polymorphisms (rs699-AGT and rs1799722-BDKRB2) and the consumption of micronutrients (sodium, magnesium, and calcium) on the BP variation. These findings contribute to the understanding of the complex mechanisms involved in BP regulation, which probable include several gene-nutrition interactions.

This study investigated the effects of non-phosphate and low-sodium (NPLS) marination on properties of white striping chicken breasts (WSCB). Chicken breasts were collected from slaughterhouse and classified as normal (NCB, n = 24) and severe WS (WSCB, n = 120). Sixty WSCB samples were vacuum-tumbled (30 min, 2 °C) with NPLS solution, containing 2.8% (w/v) potassium bicarbonate, 2.9% (w/v) potassium chloride, and 1.5% (w/v) sorbitol at the ratio of meat-to-marinade of 4 to 1 (w/w). The other 60 WSCB received no marination were assigned as nonmarinated WSCB. Properties of marinated (n = 12) and nonmarinated (n = 12) WSCB samples were determined at 0, 3, 7, 10, and 14 days of the storage at 4 °C. Properties of the NCB were also determined on day 0. Concerning day 0, the marinated WSCB exhibited higher (p < 0.05) pH, moisture content, total cooked yield, protein solubility, hardness, cohesiveness, and chewiness along with lower (p < 0.05) cooked loss, expressible water, and shear force than those of nonmarinated WSCB and NCB. Based on nuclear magnetic resonance spectroscopy, bound, intra-myofibrillar, and extra-myofibrillar water of cooked marinated WSCB were greater (p < 0.05) than those of cooked nonmarinated WSCB. The greater (p < 0.05) weight loss, moisture content, and total cooking yield were observed in marinated samples compared to those of nonmarinated WSCB throughout the storage period. Although microbial stability was reduced (p < 0.05), no difference (p ≥ 0.05) in lipid oxidation was detected between the treatments. The findings suggest the NPLS marination as a promising process for improving water holding capacity of the WSCB. PRACTICAL APPLICATION: This study presents the promising application of non-phosphate, low-sodium (NPLS) marination combined with vacuum-tumbling in improving water holding capacity of chicken breast meat affected with white striping condition. Although microbial stability of the marinated breast was negatively affected, no adverse impacts on lipid oxidation was observed during storage up to 14 days., (© 2021 Institute of Food Technologists®.)

Aim to compare the home blood pressure monitoring (HBPM) and visit blood pressure monitoring in a clinical phase I single-arm pilot trial. The 18% sodium substitute salt was used in 43 hypertensives for 8 weeks, and visited once a week, while weekly visit blood (VBP) pressure, daily home blood pressure (HBP) and urine test results before and after intervention were collected. 43 hypertensive patients were recruited, 4 were lost. And enrolled 39 patients for analysis. The VBP were lower than morning HBP and night HBP (P < 0.05). And VBP was good correlated with morning BP (SBP: r = 0.692, P < 0.001, DBP: r = 0.789, P < 0.001) and night BP (SBP: r = 0.571, P < 0.001, DBP: r = 0.738, P < 0.001). The results of mixed linear model analysis showed that patients' visit SBP (- 11.4 mmHg, 95% CI: - 17.0 to - 5.7, P < 0.001), morning home SBP (- 10.0 mmHg, 95% CI: - 16.4 to - 3.6, P = 0.003) and night home SBP (- 10.2 mmHg, 95% CI: - 15.8 to - 4.6, P = 0.001) decreased significantly, after intervention. Both HBP and VBP showed that 18% substitute salt intervention could decrease the blood pressure of hypertensives. Medication led to VBP lower than HBP, but the two still had a good correlation.Trial registration: NCT03226327. Registered 21 July 2017-Retrospectively registered, http://www.clinicaltrials.gov .

Objectives: To investigate the role of sodium in intravesical absorption of water in the bladder and the sodium pathway in the urothelium., Methods: Adult female Sprague-Dawley rats received either saline or a 5% glucose solution injection into their bladders. The changes in intravesical fluid volume; concentrations of sodium and chlorine and osmolality; and expression of aquaporin-2, epithelial sodium channel, and claudins were compared after 3 hours., Results: Intravesical volume decreased significantly in the saline group compared to that in the 5% glucose solution group. The expression of claudin-3 and -6 was higher in the saline group than in the glucose group. There was a significant correlation between changes in the intravesical saline volume and the concentration of sodium and chlorine. Intravesical administration of amiloride did not affect changes in the fluid volume and concentration of sodium., Conclusions: The presence of sodium is important for the absorption of intravesical fluid through aquaporin-2 in the urinary bladders of rats. Claudin-3 and -6 may be associated with the transport of sodium through the bladder urothelium., (© 2020 John Wiley & Sons Australia, Ltd.)

Oxidative stress produced by adjuvant treatments is associated with cell injury; however, a healthy diet can help mitigate it. The aim of this study is to investigate the association between diet quality and oxidative stress parameters in women subjected to adjuvant treatment for breast cancer. The sample comprised 70 women. Oxidative stress biomarkers and diet quality parameters based on the Brazilian Healthy Eating Index-Revised (BHEI-R)-were evaluated at baseline (p0) and after adjuvant treatment (p1). Ferric reducing antioxidant potential (FRAP) was associated with diet quality at p0. BHEI-R scores were not different between p0 and p1; however, scores from total vegetables, total fruits, milk and dairy products, and meat, eggs and legumes were lower during treatment. On the other hand, lower sodium and saturated fat intake observed at p1 counterbalanced the BHEI-R score. Oxidative stress parameters have increased at p1, but they were not associated with diet quality; thus, changes in component intake were not enough to promote changes in oxidative stress during treatment. It appears that diet can enhance patients' antioxidant defense before treatment, which could lead to better outcomes in the long term. Further investigations may help to clarify the association between diet and oxidative stress in women with breast cancer.

This study investigated the efficacy of ingesting an oral rehydration solution (DD) that has a high electrolyte concentration after exercise on fluid balance and cycling performance in comparison with a sports drink (SD) and water (WA). Nine healthy males aged 24 ± 2 years (mean ± SD), with peak oxygen uptake (VO 2 peak) 55 ± 6 mL·kg -1 ·min -1 completed three experimental trials in a randomised manner ingesting WA, SD (carbohydrates: 62 g·L -1 , sodium: 31 ± 3 mmol·L -1 ) or DD (carbohydrates: 33 g·L -1 , sodium: 60 ± 3 mmol·L -1 ). On all trials, fluid was ingested during 75 min cycling at 65% VO 2 peak (temperature: 30.4 ± 0.3 °C, relative humidity: 76 ± 1%, simulated wind speed: 8.0 ± 0.6 m·s -1 ) and during 2 h of recovery (temperature: 23.0 ± 1.0 °C, relative humidity: 67 ± 2%), with the total volume equivalent to 150% of sweat loss during the ride. A 45 min pre-load cycling time trial at a 65% VO 2 peak followed by a 20 km time trial was conducted after a further 3 h of recovery. Fluid retention was higher with DD (30 ± 15%) than WA (-4 ± 19%; p < 0.001) and SD (10 ± 15%; p = 0.002). Mean ratings of palatability were similar among drinks (WA: 4.25 ± 2.60; SD: 5.61 ± 1.79; DD: 5.40 ± 1.58; p = 0.33). Although time trial performance was similar across all three trials (WA: 2365 ± 321 s; SD: 2252 ± 174 s; DD: 2268 ± 184 s; p = 0.65), the completion time was faster in eight participants with SD and seven participants with DD than with WA. Comparing SD with DD, completion time was reduced in five participants and increased in four participants. DD was more effective at restoring the fluid deficit during recovery from exercise than SD and WA without compromising the drink's palatability with increased sodium concentration. Most individuals demonstrated better endurance exercise time trial performance with DD and SD than with WA.

Age-related cataract (ARC) development is associated with loss of crystalline lens transparency related to interactions between genetic and environmental factors. We hypothesized that polygenetic risk scores (PRS) of the selected genetic variants among the ARC-related genes might reveal significant genetic impacts on ARC risk, and the PRS might have gene-gene and gene-lifestyle interactions. We examined the hypothesis in 1972 and 39,095 subjects aged ≥50 years with and without ARC, respectively, in a large-scale hospital-based cohort study conducted from 2004 to 2013. Single nucleotide polymorphisms (SNPs) of the genes related to ARC risk were identified, and polygenetic risk scores (PRS) were generated based on the results of a generalized multifactor dimensionality reduction analysis. Lifestyle interactions with PRS were evaluated. The PRS derived from the best model included the following six SNPs related to crystallin metabolism: ULK4 &#95;rs1417380362, CRYAB &#95;rs2070894, ACCN1 &#95;rs55785344, SSTR2 &#95;rs879419608, PTN &#95;rs322348, and ICA1 &#95;rs200053781. The risk of ARC in the high-PRS group was 2.47-fold higher than in the low-PRS group after adjusting for confounders. Age, blood pressure, and glycemia interacted with PRS to influence the risk of ARC: the incidence of ARC was much higher in the elderly (≥65 years) and individuals with hypertension or hyperglycemia. The impact of PRS on ARC risk was greatest in middle-aged individuals with hypertension or hyperglycemia. Na, coffee, and a Western-style diet intake also interacted with PRS to influence ARC risk. ARC risk was higher in the high-PRS group than in the low-PRS group, and high Na intake, Western-style diet, and low coffee intake elevated its risk. In conclusion, ARC risk had a positive association with PRS related to crystallin metabolism. The genetic impact was greatest among those with high Na intake or hypertension. These results can be applied to precision nutrition interventions to prevent ARC.

Background: Aging is associated with a progressive difficulty to maintain ion regulation, which might impair the capacity for muscle contraction. Thus, the aim of this study was to examine the association between 5-year changes in dietary intake of sodium and potassium and changes in physical performance among older adults., Methods: We performed a prospective study with 868 participants from the Seniors-ENRICA cohort. Diet was measured with a validated diet history and physical performance was measured with the Short Physical Performance Battery (SPPB), both in 2012 and 2017. Analyses were performed with linear regression models adjusted for sociodemographic variables, lifestyle, and morbidity, using changes in the intake of sodium and potassium and changes in the sodium/potassium ratio during follow-up as independent variables, and the continuous change in the SPPB score as the dependent variable., Results: Over 5 years of follow-up, a 1 SD increase in sodium intake (ie, 0.73 g/d) was associated with a 0.13 (95% confidence interval [CI]: 0.26-0.01) points reduction in the SPPB score, while a 1 SD increase in potassium intake (ie, 0.70 g/d) was associated with a 0.19 (0.05-0.34) points increment in the score. In addition, a 1 SD increase in the sodium-to-potassium ratio (ie, 0.30) was associated with worse SPPB (-0.58 [-0.95 to -0.21]). Participants who adhered to dietary recommendations for minerals at baseline but became noncompliant during follow-up decreased their result in the SPPB., Conclusion: An increase of dietary sodium intake, a decrease of potassium intake and the resulting increment in the sodium-to-potassium ratio were prospectively associated with worse physical performance in older adults., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dietary sodium intake has received considerable attention as a potential risk factor of cardiovascular disease. However, evidence on the dose-response association between dietary sodium intake and cardiovascular disease risk is unclear. Embase and PubMed were searched from their inception to 17 August 2020 and studies that examined the association between sodium intake and cardiovascular disease in adolescents were not included in this review. We conducted a meta-analysis to estimate the effect of high sodium intake using a random effects model. The Newcastle-Ottawa Scale assessment was performed. A random-effects dose-response model was used to estimate the linear and nonlinear dose-response relationships. Subgroup analyses and meta-regression were conducted to explain the observed heterogeneity. We identified 36 reports, which included a total of 616,905 participants, and 20 of these reports were also used for a dose-response meta-analysis. Compared with individuals with low sodium intake, individuals with high sodium intake had a higher adjusted risk of cardiovascular disease (Rate ratio: 1.19, 95% confidence intervals = 1.08-1.30). Our findings suggest that there is a significant linear relationship between dietary sodium intake and cardiovascular disease risk. The risk of cardiovascular disease increased up to 6% for every 1 g increase in dietary sodium intake. A low-sodium diet should be encouraged and education regarding reduced sodium intake should be provided.

Objectives: Amphotericin-B (d-AmB) has a broader anti-fungal spectrum and is used for neonatal invasive-fungal-infections especially invasive-candidiasis (IC). To prevent d-AmB-induced nephrotoxicity, renal protective effect of fluid and electrolyte management has been established among adults; in this study, the authors determined this effect among neonates., Methods: In this retrospective cohort study, the authors reviewed neonatal medical records, admitted to neonatal intensive care unit and received d-AmB therapy. Patients were divided into, renal-insufficiency-group (RIG) and the non-renal-insufficiency-group (NIG)., Results: A total of 90 cases were analyzed, 41 composed RIG and 49 NIG. Renal insufficiency (RI) was developed on 1.7 (0.84) and 7.8 (1.21) days of d-AmB therapy in 26 (63%) and 15 (37%) cases respectively. Bivariate and multivariate analysis demonstrate that >4 m Eq/kg/d sodium intake across all-time points was significantly ( p < 0.0001) associated with reduced risk of RI [(phase-I: AOR: 0.96; 95% CI: 0.91-0.99), (phase-II: AOR: 0.84; 95% CI: 0.68-0.92) and (phase-III: AOR: 0.90; 95% CI: 0.86-0.95)]. While adequate fluid intake reduced the likelihood of RI if started before and initial 2 days of d-AmB therapy., Conclusions: Adequate hydration before and 48 hours after d-AmB therapy and >4 mEq/kg/day sodium intake before and through d-AmB therapy may protect neonatal RI.

Background: National drug shortages of essential medications for childhood cancer have increasingly posed a challenge in the treatment of patients. The efficacy of standardized supportive care practices to avoid treatment-related toxicities may be limited during these drug shortages. High-dose methotrexate (HDMTX) plays a critical role in modern treatment protocols for acute lymphoblastic leukemia and requires stringent supportive care measures to mitigate toxicity. As the result of a national intravenous (IV) sodium bicarbonate shortage, institutional standard HDMTX supportive care guidelines had to be modified. We describe the unanticipated consequences on HDMTX clearance., Methods: We performed a retrospective chart review assessing the impact of alternative compositions of IV fluids on the mean 24-h methotrexate levels (Cp ss ) of 25 patients receiving 76 total HDMTX infusions at Texas Children's Hospital Cancer Center from March to October 2017. During the sodium bicarbonate drug shortage, all patients received IV hydration consisting of either dextrose 5%, 0.45% normal saline (D5 ½ NS-Group A) or dextrose 5%, 0.2% normal saline (D5 ¼ NS-Group B)., Results: Patients receiving a higher total sodium dose demonstrated significantly lower Cp ss (25.36 ± 16.6 μMol) compared to patients receiving less sodium (53.9 ± 37.9 μMol; P < .001)., Conclusions: Our report shows that in the setting of IV sodium bicarbonate shortage, the composition of hydration IV fluids may affect methotrexate clearance. Patient who received a higher sodium load had a lower 24-h methotrexate level. This demonstrates the potential for unanticipated outcomes resulting from national drug shortages., (© 2020 Wiley Periodicals, Inc.)

Background: Methionine is an essential amino acid (AA) with many fundamental roles. Humans often supplement l-Met, whereas dl-Met and dl-2-hydroxy-4-(methylthio)butanoic acid (dl-HMTBA) are more frequently used to supplement livestock., Objectives: The study aimed to investigate whether dietary Met source alters the absorptive capacity for Met isomers in the small intestine of piglets., Methods: A total of 27 male 10-wk-old piglets in 3 feeding groups received a diet supplemented with 0.21% dl-Met, 0.21% l-Met, or 0.31% dl-HMTBA to meet the Met + cystine requirement. After ≥10 d, absorptive fluxes of d-Met or l-Met were measured at a physiological concentration of 50 μM and a high concentration of 5 mM in duodenum, middle jejunum, and ileum ex vivo. Data were compared by 2-factor ANOVA., Results: Across diets, fluxes of both Met isomers at both tested concentrations increased from duodenum to ileum by a factor of ∼2-5.5 (P < 0.05). Pigs supplemented with dl-Met had greater (P < 0.085) absorptive fluxes at 50 μM l-Met (0.50, 2.07, and 3.86 nmol · cm-2 · h-1) and d-Met (0.62, 1.41, and 1.19 nmol · cm-2 · h-1) than did pigs supplemented with dl-HMTBA (l-Met: 0.28, 0.76, and 1.08 nmol · cm-2 · h-1; d-Met: 0.34, 0.58, and 0.64 nmol · cm-2 · h-1) in duodenum, jejunum, and ileum, respectively. Only in jejunum of dl-Met-fed pigs, fluxes at 50 μM l-Met were reduced by the omission of luminal Na+ (from 3.27 to 0.86 nmol · cm-2 · h-1; P < 0.05) and by a cocktail of 22 luminal AAs (to 1.05 nmol · cm-2 · h-1; P < 0.05)., Conclusions: Dietary supplementation of dl-Met increases the efficiency of l-Met and d-Met absorption at physiologically relevant luminal Met concentrations along the small intestine of pigs, including a very prominent induction of an Na+-dependent transport system with preference for l-Met in the mid-jejunum. Dietary supplementation with dl-Met could be a promising tool to improve the absorption of Met and other AAs., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

The suprachiasmatic nucleus (SCN) serves as the body's master circadian clock that adaptively coordinates changes in physiology and behaviour in anticipation of changing requirements throughout the 24-h day-night cycle 1-4 . For example, the SCN opposes overnight adipsia by driving water intake before sleep 5,6 , and by driving the secretion of anti-diuretic hormone 7,8 and lowering body temperature 9,10 to reduce water loss during sleep 11 . These responses can also be driven by central osmo-sodium sensors to oppose an unscheduled rise in osmolality during the active phase 12-16 . However, it is unknown whether osmo-sodium sensors require clock-output networks to drive homeostatic responses. Here we show that a systemic salt injection (hypertonic saline) given at Zeitgeber time 19-a time at which SCN VP (vasopressin) neurons are inactive-excited SCN VP neurons and decreased non-shivering thermogenesis (NST) and body temperature. The effects of hypertonic saline on NST and body temperature were prevented by chemogenetic inhibition of SCN VP neurons and mimicked by optogenetic stimulation of SCN VP neurons in vivo. Combined anatomical and electrophysiological experiments revealed that osmo-sodium-sensing organum vasculosum lamina terminalis (OVLT) neurons expressing glutamic acid decarboxylase (OVLT GAD ) relay this information to SCN VP neurons via an excitatory effect of γ-aminobutyric acid (GABA). Optogenetic activation of OVLT GAD neuron axon terminals excited SCN VP neurons in vitro and mimicked the effects of hypertonic saline on NST and body temperature in vivo. Furthermore, chemogenetic inhibition of OVLT GAD neurons blunted the effects of systemic hypertonic saline on NST and body temperature. Finally, we show that hypertonic saline significantly phase-advanced the circadian locomotor activity onset of mice. This effect was mimicked by optogenetic activation of the OVLT GAD → SCN VP pathway and was prevented by chemogenetic inhibition of OVLT GAD neurons. Collectively, our findings provide demonstration that clock time can be regulated by non-photic physiologically relevant cues, and that such cues can drive unscheduled homeostatic responses via clock-output networks.

Background: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload., Methods: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging., Results: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake., Conclusions: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status., Clinical Trial Registry Name and Registration Number: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998., (Copyright © 2020 by the American Society of Nephrology.)

Objective: Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure., Methods: We studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression., Results: Baseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson's r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98-1.06)., Conclusion: UCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone., Competing Interests: This work was supported by a research grant from Astellas to JvdL and MBR. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In the past, ultramarathon runners have commonly believed that consuming sodium supplements, as capsules or tablets, will prevent exercise-associated hyponatremia (EAH), dehydration, muscle cramping, and nausea, but accumulating evidence indicates that sodium supplementation during ultramarathons is not necessary and may be potentially dangerous. In this work, beliefs about whether sodium supplements should be made available at ultramarathons were assessed during 2018 among 1152 participants of the Ultrarunners Longitudinal TRAcking (ULTRA) study, of which 85.2% had completed an ultramarathon during 2014-2018. Two-thirds (66.4%) of study participants indicated that sodium supplements should be made available at ultramarathons, supported by beliefs that they prevent EAH (65.5%) and muscle cramping (59.1%). Of those indicating that sodium supplements should not be made available, 85.0% indicated it is because runners can provide their own, 27.9% indicated it is because they are not necessary, and 12.1% indicated they could increase thirst drive and cause overhydration. In general, there was a tendency for those who were older, less active in running ultramarathons in recent years, and with a longer history of ultramarathon running to be less likely to know that sodium supplements do not help prevent EAH, muscle cramping, and nausea. Novelty Ultramarathon runners continue to have misunderstandings about the need for sodium supplementation during ultramarathons. Few ultramarathon runners recognize that supplementing sodium intake beyond that in food and drink is generally not necessary during ultramarathons or that it could result in overhydration. Continued educational efforts are warranted to help ensure safe participation in the sport.

The relationship between salt intake and cardiovascular diseases is a contemporary scientific controversy, which has been attributed to the limits of the measures of salt intake used in the studies. Thus, this article sought to systematically review the literature on the methods used to estimate salt intake in different study designs. Of the 124 articles, 60.5% used only biochemical measures, 26.6% only self-report measures and 12.9% reported the combined use of both methods. The 24-hour urinary sodium excretion was the predominant biochemical method (79.1%) and the Food Frequency Questionnaire was the predominant self-report measure (36.4%). Interventional studies used mostly 24-hour urinary sodium excretion; while longitudinal studies used self-report measures. The question guiding the study and its design, as well as constraints related to costs, sample size and feasibility seems to influence the choice of the type of measurement.

Objective: Pleurex catheters are a form of palliative therapy for patients, offering relief from symptomatic ascites while also affording greater independence and flexibility; however, aggressive drainage can lead to significant total body sodium losses. We describe the course of patients with "Pleurex desalination," an under-appreciated cause of hypovolemic hyponatremia, highlighting its unique pathophysiology and providing recommendations on how to manage these complex patients., Patients and Methods: We included representative patients with "Pleurex desalination" who were evaluated and treated by the renal consult service at Brigham and Women's between 2017 and 2019., Results: We identified 3 patients who were hospitalized with "Pleurex desalination" and had complete data on serum and urine studies, as well as treatment course. We demonstrate that patients with "Pleurex desalination" were removing up to 1 to 2 L of ascitic fluid a day and were admitted with signs and symptoms of profound hypovolemia and hyponatremia. Patients worsened with administration of diuretics and salt restriction and improved with aggressive fluid resuscitation in the form of hypertonic saline, normal saline, and/or intravenous albumin., Conclusion: "Pleurex desalination" is an under-recognized cause of hyponatremia; at-risk patients require close observation and periodic resuscitation with intravenous, volume-expanding fluids.

Background: While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking., Objectives: We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms., Methods: We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger)., Results: Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01)., Conclusions: These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555., (Copyright © American Society for Nutrition 2019.)

Gitelman syndrome is an inherited tubulopathy characterized by renal salt wasting from the distal convoluted tubule. Defects in the sodium chloride cotransporter (encoded by SLC12A3) underlie this autosomal recessive condition. This article focuses on the specific challenges of diagnosing and treating Gitelman syndrome, with use of an illustrative case report. Symptoms relate to decreased serum potassium and magnesium levels, which include muscle weakness, tetany, fatigue and palpitations. Sudden cardiac deaths have been reported. Making a diagnosis may be difficult given its rarity but is important. A knowledge of the serum and urine biochemical picture is vital to distinguish it from a broad differential diagnosis, and application of genetic testing can resolve difficult cases. There is a group of Gitelman syndrome heterozygous carriers that experience symptoms and electrolyte disturbance and these patients should be managed in a similar way, though here genetic investigations become key in securing a difficult diagnosis. Potassium and magnesium replacement is the cornerstone of treatment, though practically this can be hard for patients to manage and often does not fully relieve symptoms even when serum levels are normalized. Challenges arise due to the lack of randomized controlled trials focussing on treatment of this rare disease; hence, clinicians endorse strategies in line with correction of the underlying pathophysiology such as sodium loading or pharmacological treatments, which seem to help some patients. Focussed dietary advice and knowing the best tolerated preparations of potassium and magnesium medications are useful tools for the physician, as well as an awareness of the specific burdens that this patient group face in order to signpost appropriate support., (© 2019 John Wiley & Sons Ltd.)

Accurately estimating nutrient intake can be challenging, yet it is important for informing policy. This cross-sectional validation study compared the use of three methods for estimating the intake of sodium, potassium, and iodine in children aged 9-11 years in New Zealand. Over the same 24 hour period, participants collected duplicate diets ( n = 37), weighed food records ( n = 84), and 24 hour urine samples ( n = 82). Important differences were found between dietary estimates of sodium, potassium, and iodine using the three methods of dietary assessment, suggesting that different methods of assessment have specific limitations for the measurement of these nutrients in children. Bland Altman plots show relatively wide limits of agreement for all measures and nutrients. These results support the World Health Organization's (WHOs) recommendations to use urinary assessment to measure population sodium and iodine intake, while dietary assessment appears to be more accurate for estimating potassium intake. Compared to reference values, our results suggest that the children in this study consume inadequate iodine, inadequate potassium, and excess dietary sodium. Public health measures to reduce sodium intake, increase intake of fruit and vegetables, and iodine-rich foods are warranted in New Zealand.

Background: Hypotonic maintenance i.v. fluids (IVF) pose a higher risk of hyponatremia than isotonic maintenance IVF, but isotonic maintenance IVF can result in excess sodium (Na) load in children. This study analyzed the incidence and risk factors for hyponatremia in children given hypotonic fluids with different Na concentrations and different maintenance rates., Methods: We performed a retrospective analysis using medical charts of children aged 3 months-15 years. The children were normonatremic (Na ≥135 mmol/L and <145 mmol/L) before IVF, and given IVF containing 35 mmol/L Na at a 100% maintenance rate (Na 35) or fluids containing 84 mmol/L Na at a 70% maintenance rate (Na 84) for 24-48 h., Results: Of a total of 463 children, hyponatremia (Na <135 mmol/L) occurred in 46/275 children (17%) given Na 35, and 16/188 (9%) given Na 84 (P = 0.01). On multivariate logistic regression analysis, Na 35 (OR, 2.19; 95%CI: 1.04-4.62), low clinical dehydration scale (CDS) score before IVF (OR, 0.17; 95%CI: 0.06-0.49), and high body temperature 24-48 h after maintenance IVF (OR, 2.39; 95%CI: 1.79-3.18) were independent risk factors for hyponatremia., Conclusions: Maintenance IVF with low Na concentration at a 100% maintenance rate, low CDS before IVF, and a high body temperature 24-48 h after maintenance IVF are independent risk factors for hyponatremia., (© 2019 Japan Pediatric Society.)

Bone is a major storage site as well as an endogenous source of lead in the human body. Dietary sodium and potassium intake may play a role in the mobilization of lead from bone to the circulation. We examined whether association between bone lead and urinary lead, a marker of mobilized lead in plasma, was modified by dietary intake of sodium and potassium among 318 men, aged 48-93 years, in the Veterans Affairs (VA) Normative Aging Study. Dietary sodium and potassium were assessed by flame photometry using 24-h urine samples, and a sodium-to-potassium ratio was calculated from the resulting measures. Patella and tibia bone lead concentrations were measured by K-shell-x-ray fluorescence. Urinary lead was measured by inductively coupled plasma mass spectroscopy in 24-h urine samples. Linear regression models were used to regress creatinine clearance-corrected urinary lead on bone lead, testing multiplicative interactions with tertiles of sodium, potassium, and sodium-to-potassium ratio, separately. After adjustment for age, body mass index, smoking, vitamin C intake, calcium, and total energy intake, participants in the highest tertile of sodium-to-potassium ratio showed 28.1% (95% CI: 12.5%, 45.9%) greater urinary lead per doubling increase in patella lead, whereas those in the second and lowest tertiles had 13.8% (95% CI: -1.7%, 31.7%) and 5.5% (95% CI: -8.0%, 21.0%) greater urinary lead, respectively ( p -for-interaction = 0.04). No statistically significant effect modification by either sodium or potassium intake alone was observed. These findings suggest that relatively high intake of sodium relative to potassium may play an important role in the mobilization of lead from bone into the circulation.

Purpose: To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders., Methods: We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints., Findings: We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601-2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI - 0.2-30.4%, p = 0.05)., Conclusions: In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.

This study aimed to evaluate the potential of two new fat-protected butyrate or heptanoate salts to improve gut health and control post-weaning colibacillosis in weaning piglets challenged with enterotoxigenic Escherichia coli (ETEC) F4 + , particularly focusing on their impact on intestinal microbiota and fermentative activity along the gastrointestinal tract (GIT). Seventy-two 21-d-old pigs were fed a plain diet (CTR) or supplemented with sodium butyrate (BUT) or sodium heptanoate (HPT), both at 0.3%. After a week of adaptation, animals were orally challenged at days 8 and 9 with 5.8 · 10 9 and 6.6 · 10 10 cfu, respectively, and were euthanised on d 4 and d 8 post-inoculation (PI) ( n = 8) to collect blood, digesta and tissue samples and characterise microbial groups, pathogen loads (qPCR), fermentation, ileal histomorphometry and immune markers. Colonic microbiota was analysed by 16S rRNA gene MiSeq sequencing. Supplementing both acid salts did not compensate clinical challenge effects nor performance impairments and neither histomorphometry nor serum biomarkers. Changes in the gastric fermentative activity were registered, BUT reducing lactic acid concentrations (day 8 PI), and with HPT fewer animals presenting detectable concentrations of propionic, butyric and valeric acids. At ileum BUT increased acetic acid concentration (day 8 PI), and both additives reduced short-chain fatty acids (SCFA) in the colon. Increases in enterobacteria and coliforms counts in ileal digesta (day 4 PI, p < 0.10) and mucosa scrapes ( p < 0.05) were registered although E. coli F4 gene copies were unaffected. Regarding changes in the colonic microbiota (day 4 PI), Prevotellaceae and Prevotella were promoted with BUT supplementation whereas only minor groups were modified in HPT-treated animals. Summarising, although the pathogen loads or inflammatory mediators remained unresponsive, butyrate and heptanoate showed a significant impact on microbial fermentation along the whole GIT, being able to modify different bacterial groups at the colon. It could be hypothesised that these effects might be mediated by a carry-over effect of the changes observed in gastric fermentation, but possibly also to a better nutrient digestion in the foregut as a result of the reduced colonic SCFA concentrations.

Sodium and chloride are the key factors maintaining normal osmotic pressure (OSM) and volume of the extracellular fluid, and influencing the acid-base balance of body fluids. The experiment was conducted to investigate the effects of dietary Na+ and Cl- level on growth performance, excreta moisture, blood biochemical parameters, intestinal Na+-glucose transporter 1 (SGLT1) messenger RNA (mRNA), and Na+-H+ exchanger 2 (NHE2) mRNA, and to estimate the optimal dietary sodium and chlorine level for yellow-feathered chickens from 22 to 42days. A total of 900 22-day-old Lingnan yellow-feathered male chickens were randomly allotted to five treatments, each of which included six replicates of 30 chickens per floor pen. The basal control diet was based on corn and soybean meal (without added NaCl and NaHCO3). Treatments 2 to 5 consisted of the basal diet supplemented with equal weights of Na+ and Cl-, constituting 0.1%, 0.2%, 0.3% and 0.4% of the diets. Supplemental dietary Na+ and Cl- improved the growth performance (P<0.05). Average daily gain (ADG) showed a quadratic broken-line regression to increasing dietary Na+ and Cl- (R2=0.979, P<0.001), and reached a plateau at 0.1%. Supplemental Na+ and Cl- increased (P<0.05) serum Na+ and OSM in serum and showed a quadratic broken-line regression (R2=0.997, P=0.004) at 0.11%. However, supplemental Na+ and Cl- decreased (P<0.05) serum levels of K+, glucose (GLU) and triglyceride. Higher levels of Na+and Cl- decreased duodenal NHE2 transcripts (P<0.05), but had no effect on ileal SGLT1 transcripts. The activity of Na+ /K+-ATPase in the duodenum decreased (P<0.05) with higher levels of dietary Na+ and Cl-. In conclusion, the optimal dietary Na+ and Cl- requirements for yellow-feathered chickens in the grower phase, from 22 to 42 days of age, to optimize ADG, serum Na+, OSM, K+ and GLU were 0.10%, 0.11%, 0.11%,0.17% and 0.16%, respectively, by regression analysis.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder characterised by orthostatic intolerance and a rise in heart rate by at least 30 bpm or an absolute heart rate value of at least 120 bpm within 10 min of standing or during a tilt table test. Overwhelmingly, POTS affects young Caucasian women, which can lead physicians to miss the diagnosis in men or non-white patients. We describe a case of 29-year-old African-American man who developed lightheadedness, generalised weakness, tachycardia and palpitations and was subsequently diagnosed with POTS. We review its clinical features, differential diagnosis, pathophysiology and treatment options. We also emphasise that POTS should be considered as a differential diagnosis in any patient presenting with typical clinical features, who may not be in the usual demographics of the disorder., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

In lifestyle intervention trials, where the goal is to change a participant's weight or modify their eating behavior, self-reported diet is a longitudinal outcome variable that is subject to measurement error. We propose a statistical framework for correcting for measurement error in longitudinal self-reported dietary data by combining intervention data with auxiliary data from an external biomarker validation study where both self-reported and recovery biomarkers of dietary intake are available. In this setting, dietary intake measured without error in the intervention trial is missing data and multiple imputation is used to fill in the missing measurements. Since most validation studies are cross-sectional, they do not contain information on whether the nature of the measurement error changes over time or differs between treatment and control groups. We use sensitivity analyses to address the influence of these unverifiable assumptions involving the measurement error process and how they affect inferences regarding the effect of treatment. We apply our methods to self-reported sodium intake from the PREMIER study, a multi-component lifestyle intervention trial., (© 2019 International Biometric Society.)

The objective of this study was to evaluate the association between sodium intake and blood pressure (BP) control in hypertensive patients taking antihypertensive medications by using 24-hour urine collection and 24-hour ambulatory BP. This is a cross-sectional community-based study and conducted in 2011 and 2012. A total of 1128 participants were recruited from five cities in Korea. Among them, 740 participants who had complete 24-hour urine collection and valid 24-hour ambulatory BP data were included in this study. Participants were divided into four groups: normotensives (NT, n = 441), untreated hypertensive patients (UTHT, n = 174), controlled hypertensive patients (CHT, n = 62), and uncontrolled hypertensive patients (UCHT, n = 63). UCHT and CHT groups showed higher mean age than NT and UTHT groups. UCHT and UTHT groups showed higher 24-hour systolic BP (SBP) and diastolic BP (DBP) than NT and CHT groups. UCHT group had the highest level of 24-hour urine sodium. Multivariate analysis adjusted with age, gender, body mass index, estimated glomerular filtration rate, and use of diuretics showed higher level of 24-hour urine sodium in UCHT group than that in CHT group. Multivariate logistic regression analysis revealed independent association of the amount of 24-hour urine sodium with uncontrolled BP in hypertensive patients on antihypertensive drug treatment. Higher level of 24-hour urine sodium excretion in uncontrolled hypertensive patients suggests that excessive sodium intake could be associated with blunted BP lowering efficacy of antihypertensive medications., (©2019 Wiley Periodicals, Inc.)

Background and Objective: Recent studies have related the consumption of ultra-processed foods with the development of cardiovascular diseases and have considered this relation with excessive sodium intake. While Brazilian studies have analysed that this consumption may have no direct relationship with the processing, but rather with the addition of salt. The purpose of this study is to investigate the contribution of the consumption of processed products in the daily intake of sodium ingestion by atherosclerotic disease patients., Methods: A sub study, conducted with data from 630 cardiopathic patients who take part in "Effect of Brazilian Cardioprotective Food Program study on the reduction of events and risk factors in secondary prevention of cardiovascular disease part". Food was classified as: unprocessed or minimally processed foods, processed culinary ingredients, processed foods, ultra-processed food and beverages. Twenty-four-hour food recall (R24h) was collected from patients, and the estimation of total calories and sodium intake were calculated, as well as the percentage of sodium contribution according to the categories already mentioned. For the adequacy ratio analysis, the daily values of sodium intake were used to compared to the recommendations of the World Health Organization (<2000 mg / day)., Results: The average sodium intake was 1970.87 mg for women and 2642.86 mg for men, being higher for males' patients aged 60-79. It was observed that 64% of the studied population demonstrated sodium intake > 2000 mg. When considered levels > 3001 mg, a higher incidence of consumption was observed in the male group. Only 21.1% were intaking sodium within the recommended amount. Industrialized foods contributed to 33% of the mineral intake., Conclusion: These findings have demonstrated that the majority of the studied patients exceeded the dietary sodium recommendation. It has also indicated that patient's male, have presented increased consumption of the mineral. Consequently, warning for the necessity of greater investments in the nutritional re-education of these patients., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Osmotic demyelination syndrome is an acute demyelination process that usually occurs several days following an osmotic stress. This syndrome is rare in adults (0.4% to 0.56%) and even more uncommon in children. We performed a review of all reported pediatric osmotic demyelination syndrome patients from 1960 to 2018. Among all 106 cases, 49 presented with isolated central pontine myelinolysis, 30 with isolated extrapontine myelinolysis, and 27 with combined central pontine myelinolysis and extrapontine myelinolysis. There was no gender preponderance, and the highest prevalence was noted between the ages one and five years. Magnetic resonance imaging remains the diagnostic modality of choice, and diffusion tensor imaging is now increasingly used for prognostication in osmotic demyelination syndrome. Sixty percent of the children had a complete neurological recovery. Current management of osmotic demyelination syndrome in children consists of supportive medical care, steroids, and intravenous immunoglobulin. Our review of the literature supports the hypothesis that steroids and immunoglobulins are potentially helpful, although additional controlled studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Reduction of salt intake is a public health priority and necessitates the surveillance of salt intake in the population. The validity of salt intake assessed by dietary surveys is generally low. We, therefore, aimed to estimate salt intake by 24-h urine collection and to assess the usefulness of spot urine collection for surveillance purposes. In the population-based Tromsø Study 2015-2016, 493 men and women aged 40-69 years collected 24-h urine, of whom 475 also collected spot urine. Sodium and potassium excretions were calculated by multiplying respective urinary concentrations by the total volume of urine. Based on the sodium concentration in spot urine, we also estimated 24-h sodium excretion by three different equations. Mean sodium excretion was 4.09 ± 1.60 and 2.98 ± 1.09 g/24-h in men and women, respectively, corresponding to a calculated salt intake of 10.4 and 7.6 g. The sodium to potassium molar (Na/K) ratio was approximately 1.8 in both genders. Of the three equation utilizing spot urine, estimated mean 24-h sodium excretion was closest for the INTERSALT formulae (4.29 and 2.96 g/24-h in men and women, respectively). In this population-based study, the estimated salt intake was higher than the recommended intake. However, urine potassium excretion was rather high resulting in a favorable Na/K ratio. Mean sodium excretion calculated from spot urine by the INTERSALT equation predicted the mean sodium excretion in 24-h urine reasonably well., Competing Interests: L.J. is a member of Mills Scientific Council H.E.M., A.E.E., H.J., and K.H. declare no conflict of interest.

The study aimed to analyse the intake of Na with cereal products by the population of Poland. In addition, based on available literature, changes in the content of Na in bread sold in the Polish market from 2009 to 2018 were analysed with regard to Na intake reduction campaigns held in Poland since 2009 popularising information about the adverse effect of sodium on the human cardiovascular system. The results led to the conclusion that the analysed products contained 3.042 ± 3.4 g of Na per 1 kg of fresh product. The content of Na in the analysed products was bread > bread rolls > grains > pasta > rice. Cereal products provide 48.3 % of an adult's intake of Na, where as much as 48.2 % is covered by bread, with only 0.04 % by grains, 0.04 % by pasta, and 0.01 % by rice. According to information available in reference literature from 2009-2017 the content of Na in baked goods has not been subject to significant modifications. In Poland, with regard to an excessive consumption of Na, efficient strategies must be developed to increase the awareness of consumers and to reduce the use of table salt in the most popular products, and in particular in baked goods. One of the ways to reduce the intake of Na would be consumers' selection of an adequate range of foodstuffs naturally poor in this element or having its content reduced by means of a suitable technology. This can be a significant component of practices preventing the development of hypertension. However, the fact that information about the content of Na in cereal products is often missing from product labels makes consumer choice difficult.

Objective: To evaluate the effects of intravenous infusion of fluids and sodium on the first day of admission on infusion of enteral nutrition in the first 5 days in intensive care patients., Methods: A prospective cohort study was conducted with critical nonsurgical patients admitted for at least 5 days who were on mechanical ventilation and receiving enteral nutrition. The amount of intravenous fluids and sodium infused on the first day and the volume of enteral nutrition infused in the first 5 days were investigated. The volume of intravenous fluids > 35mL/kg or ≤ 35mL/kg of body weight and sodium (above or below the 25th percentile) infused on the first day was compared with infused enteral nutrition., Results: A total of 86 patients were studied, with a mean (± standard deviation) of 65 ± 17 years, of which 54.7% were female. On the first day, 3,393.7 ± 1,417.0mL of fluid (48.2 ± 23.0mL/kg) and 12.2 ± 5.1g of sodium were administered. Fifty-eight (67.4%) patients received more than 35mL/kg of fluids. In 5 days, 67 ± 19.8% (2,993.8 ± 1,324.4mL) of the prescribed enteral nutrition was received. Patients who received > 35mL/kg of intravenous fluids also received less enteral nutrition in 5 days (2,781.4 ± 1,337.9 versus 3,433.6 ± 1,202.2mL; p = 0.03) versus those who received ≤ 35mL/kg. Patients with intravenous sodium infusion above the 25th percentile (≥ 8.73g) on the first day received less enteral nutrition volume in 5 days (2,827.2 ± 1,398.0 versus 3,509.3 ± 911.9mL; p = 0.02)., Conclusion: The results of this study support the assumption that the administration of intravenous fluids > 35mL/kg and sodium ≥ 8.73g on the first day of hospitalization may contribute to the lower infusion of enteral nutrition in critically ill patients.

Background: Although salt taste preference is malleable in adults, no research to date has focused on children, whose dietary sodium intake exceeds recommended intake and whose salt taste preferences are elevated., Objective: This proof-of-principle trial determined whether 8-wk exposure to low-sodium cereal (LSC) increased children's acceptance of its taste and changed their salty and sweet taste preferences., Methods: Children (n = 39; ages 6-14 y; 67% female) were randomly assigned to ingest LSC or regular-sodium cereal (RSC) 4 times/wk for 8 wk. The cereals, similar in sugar (3 g/cup compared with 2 g/cup) and energy content (100 kcal/cup) yet different in sodium content (200 mg sodium/cup compared with 64 mg sodium/cup), were chosen based on taste evaluation by a panel of children. Mothers completed daily logs on children's cereal intake. At baseline and after the exposure period, taste tests determined which cereal children preferred and measured children's most preferred amount of salt (primary outcomes), and most preferred amount of sucrose and salt taste detection thresholds (secondary outcomes). Repeated measures ANOVAs were conducted on primary and secondary outcomes, and generalized estimating equations were conducted on amount of cereal ingested at home over time., Results: Both treatment groups accepted and ate the assigned cereal throughout the 8-wk exposure. There were no group × time interactions in salt detection thresholds (P = 0.32) or amount of salt (P = 0.30) and sucrose (P = 0.77) most preferred, which were positively correlated (P = 0.001). At baseline and after the exposure, the majority in both groups preferred the taste of the RSC relative to LSC (P > 0.40)., Conclusions: Children showed no change in salt preference but readily ate the LSC for 8 consecutive weeks. Findings highlight the potential for reducing children's dietary salt intake by incorporating low-sodium foods in the home environment without more preferred higher-salt versions of these foods. This trial was registered at clinicaltrials.gov as NCT02909764., (Copyright © American Society for Nutrition 2019.)

Background: The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies., Objectives: The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population., Methods: Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed., Results: In study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4)., Conclusions: Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension. This study was registered at PROSPERO 2015 as CRD42015017773., (Copyright © American Society for Nutrition 2019.)