Trimetazidine Protects from Mercury-Induced Kidney Injury.

INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.

High Salt Diet Impacts the Risk of Sarcopenia Associated with Reduction of Skeletal Muscle Performance in the Japanese Population.

The World Health Organization has recommended 5 g/day as dietary reference intakes for salt. In Japan, the averages for men and women were 11.0 g/day and 9.3 g/day, respectively. Recently, it was reported that amounts of sodium accumulation in skeletal muscles of older people were significantly higher than those in younger people. The purpose of this study was to investigate whether the risk of sarcopenia with decreased muscle mass and strength was related to the amount of salt intake. In addition, we investigated its involvement with renalase. Four groups based on age and salt intake ("younger low-salt," "younger high-salt," "older low-salt," and "older high-salt") were compared. Stratifying by age category, body fat percentage significantly increased in high-salt groups in both younger and older people. Handgrip strength/body weight and chair rise tests of the older high-salt group showed significant reduction compared to the older low-salt group. However, there was no significant difference in renalase concentrations in plasma. The results suggest that high-salt intake may lead to fat accumulation and muscle weakness associated with sarcopenia. Therefore, efforts to reduce salt intake may prevent sarcopenia.

Sodium and Salt Consumption in Latin America and the Caribbean: A Systematic-Review and Meta-Analysis of Population-Based Studies and Surveys.

Sodium/salt consumption is a risk factor for cardiovascular diseases. Although global targets to reduce salt intake have been established, current levels and trends of sodium consumption in Latin America and the Caribbean (LAC) are unknown. We conducted a systematic review and meta-analysis of population-based studies in which sodium consumption was analyzed based on urine samples (24 hour samples or otherwise). The search was conducted in Medline, Embase, Global Health, Scopus and LILACS. From 2350 results, 53 were studied in detail, of which 15 reports were included, providing evidence for 18 studies. Most studies were from Brazil (7/18) and six collected 24 hour urine samples. In the random effects meta-analysis, 12 studies (29,875 people) were analyzed since 2010. The pooled mean 24 hour estimated sodium consumption was 4.13 g/day (10.49 g/day of salt). When only national surveys were analyzed, the pooled mean was 3.43 g/day (8.71 g/day of salt); when only community studies were analyzed the pooled mean was 4.39 g/day (11.15 g/day of salt). Studies had low risk of bias. The estimated 24 hour sodium consumption is more than twice the World Health Organization recommendations since 2010. Regional organizations and governments should strengthen policies and interventions to measure and reduce sodium consumption in LAC.

Transcriptome Sequencing to Detect the Potential Role of Long Noncoding RNAs in Salt-Sensitive Hypertensive Rats.

BACKGROUNDS: Long noncoding RNAs (lncRNAs) play an important role in various biological processes. However, their functions in salt-sensitive hypertension are largely unknown. In this study, the lncRNA-seq technique was employed to compare the expression profiles of lncRNAs and mRNAs in salt-sensitive hypertensive rats. METHODS: Blood pressure, serum sodium, and urinary creatinine were texted in salt-sensitive and salt-insensitive rats fed with different salt concentrations. High-throughput sequencing was used to detect the expression of lncRNAs and mRNA in the renal medulla of the two groups. RESULTS: Blood pressure and urinary sodium/creatinine of high-salt diets of the sensitive group were significantly higher than that in the control group. Serum sodium has no significant difference between the two groups in high-salt diets. NONRATG007131.2 and NONRATG012674.2 were the most different lncRNAs in the high salt-sensitive group. Correlation analysis reveals that Matn1, Serpinb12, Anxa8, and Hspa5 may play an important role in salt-sensitive hypertension. CONCLUSION: This study analyzed the difference in lncRNA and mRNA between salt-sensitive and salt-insensitive rats with different salt diets by high-throughput sequencing. Salt sensitivity and salt concentration were two key factors for the induction of hypertension. We found some potential genes that play an important role in salt-sensitive hypertension.

Formulas to Estimate Dietary Sodium Intake From Spot Urine Alter Sodium-Mortality Relationship.

To study the effect of formulas on the estimation of dietary sodium intake (sodium intake) and its association with mortality, we analyzed the TOHP (Trials of Hypertension Prevention) follow-up data. Sodium intake was assessed by measured 24-hour urinary sodium excretion and estimations from sodium concentration using the Kawasaki, Tanaka, and INTERSALT (International Cooperative Study on Salt, Other Factors, and Blood Pressure) formulas. We used both the average of 3 to 7 urinary measurements during the trial period and the first measurement at the beginning of each trial. Additionally, we kept sodium concentration constant to test whether the formulas were independently associated with mortality. We included 2974 individuals aged 30 to 54 years with prehypertension, not assigned to sodium intervention. During a median 24-year follow-up, 272 deaths occurred. The average measured sodium intake was 3766±1290 mg/d. All estimated values, including those with constant sodium concentration, were systematically biased with overestimation at lower levels and underestimation at higher levels. There was a significant linear association between the average measured sodium intake (ie, gold standard method) and mortality. This relationship was altered by using the estimated sodium intakes. There appeared to be a J- or U-shaped relationship for the average estimated sodium by all formulas. Despite variations in the sodium-mortality relationship among various formulas, a common pattern was that all estimated values including those with constant sodium appeared to be inversely related to mortality at lower levels of sodium intake. These results demonstrate that inaccurate estimates of sodium cannot be used in association studies, particularly as the formulas per se seem to be related to mortality independent of sodium.

Rapid weight loss with dietary salt restriction in hospitalized patients with chronic kidney disease.

Dietary salt restriction is essential for managing fluid retention in patients with chronic kidney disease (CKD). In this retrospective cohort study, we investigated weight loss from the perspective of fluid status in CKD patients during a 7-day hospitalization period while consuming a low-salt diet (5 g/day). Among 311 patients, the median weight loss (interquartile range, maximum) was 0.7 (0.0-1.4, 4.7) kg on Day 4 and 1.0 (0.3-1.7, 5.9) kg on Day 7. Patients were classified into quartiles based on pre-hospital urinary salt excretion (quartile [Q] 1, 1.2-5.7; Q2, 5.8-8.4; Q3, 8.5-11.3; Q4, 11.4-29.2 g/day). Weight loss was significantly greater in Q3 and Q4 than in Q1. The body mass index (BMI) and urinary salt excretion in the first 24 hours after admission were independently associated with rapid weight loss on Day 4 by multivariate logistic regression analysis. In conclusion, CKD patients with a high salt intake or high BMI exhibit rapid weight loss within a few days of consuming a low-salt diet. Dietary salt restriction is effective for reducing proteinuria in these patients, but long-term observation is needed to confirm the sustained effects.

Superoxide increases surface NKCC2 in the rat thick ascending limbs via PKC.

The apical Na+-K+-2Cl- cotransporter (NKCC2) mediates NaCl reabsorption by the thick ascending limb (TAL). The free radical superoxide ( O2- ) stimulates TAL NaCl absorption by enhancing NKCC2 activity. In contrast, nitric oxide (NO) scavenges O2- and inhibits NKCC2. NKCC2 activity depends on the number of NKCC2 transporters in the TAL apical membrane and its phosphorylation. We hypothesized that O2- stimulates NKCC2 activity by enhancing apical surface NKCC2 expression. We measured surface NKCC2 expression in rat TALs by surface biotinylation and Western blot analysis. Treatment of TALs with O2- produced by exogenous xanthine oxidase (1 mU/ml) and hypoxanthine (500 µM) stimulated surface NKCC2 expression by ~18 ± 5% (P < 0.05). O2- -stimulated surface NKCC2 expression was blocked by the O2- scavenger tempol (50 µM). Scavenging H2O2 with 100 U/ml catalase did not block the stimulatory effect of xanthine oxidase-hypoxanthine (22 ± 8% increase from control, P < 0.05). Inhibition of endogenous NO production with Nω-nitro-l-arginine methyl ester enhanced surface NKCC2 expression by 21 ± 6% and, when added together with xanthine oxidase-hypoxanthine, increased surface NKCC2 by 41 ± 10% (P < 0.05). Scavenging O2- with superoxide dismutase (300 U/ml) decreased this stimulatory effect by 60% (39 ± 4% to 15 ± 10%, P < 0.05). Protein kinase C inhibition with Gö-6976 (100 nM) blocked O2- -stimulated surface NKCC2 expression (P < 0.05). O2- did not affect NKCC2 phosphorylation at Thr96/101 or its upstream kinases STE20/SPS1-related proline/alanine-rich kinase-oxidative stress-responsive kinase 1. We conclude that O2- increases surface NKCC2 expression by stimulating protein kinase C and that this effect is blunted by endogenous NO. O2- -stimulated apical trafficking of NKCC2 may be involved in the enhanced surface NKCC2 expression observed in Dahl salt-sensitive rats.

Mean Dietary Salt Intake in Vanuatu: A Population Survey of 755 Participants on Efate Island.

Non-communicable diseases are responsible for 63% of global deaths, with a higher burden in low- and middle-income countries. Hypertension is the leading cause of cardiovascular-disease-related deaths worldwide, and approximately 1.7 million deaths are directly attributable to excess salt intake annually. There has been little research conducted on the level of salt consumption amongst the population of Vanuatu. Based on data from other Pacific Island countries and knowledge of changing regional diets, it was predicted that salt intake would exceed the World Health Organization's (WHO) recommended maximum of 5 g per day. The current study aimed to provide Vanuatu with a preliminary baseline assessment of population salt intake on Efate Island. A cross-sectional survey collected demographic, clinical, and urine data from participants aged 18 to 69 years in rural and urban communities on Efate Island in October 2016 and February 2017. Mean salt intake was determined to be 7.2 (SD 2.3) g/day from spot urine samples, and 5.9 (SD 3.6) g/day from 24-h urine samples, both of which exceed the WHO recommended maximum. Based on the spot urine samples, males had significantly higher salt intake than females (7.8 g compared to 6.5 g; p < 0.001) and almost 85% of the population consumed more than the WHO recommended maximum daily amount. A coordinated government strategy is recommended to reduce salt consumption, including fiscal policies, engagement with the food industry, and education and awareness-raising to promote behavior change.

An expert recommendation on salt intake and blood pressure management in Chinese patients with hypertension: A statement of the Chinese Medical Association Hypertension Professional Committee.

The occurrence of hypertension is influenced by combined actions of genetic and environmental factors. Among environmental factors, high salt intake is considered as one of the most important and critical dietary factors. High salt intake is closely related to the incidence and mortality of cardiac and cerebrovascular events, as well as ventricular hypertrophy, renal damage, and other target organ damages. The existing data show that the daily sodium salt intake of Chinese population is significantly higher than that of European and American populations, and it generally exceeds the standard. Therefore, sodium and potassium intake in patients with hypertension should be actively assessed to carry out targeted treatment, which is an important strategy in blood pressure management. According to the characteristics of high prevalence of hypertension, high sodium salt intake, and low blood pressure control rate in China, Chinese Medical Association Hypertension Professional Committee believes that it is necessary to promote salt restriction and formulate the assessment of salt intake and clinical process of blood pressure management according to the current status of sodium intake.

Sex-specific patterns in the association between salt intake and blood pressure: The ELSA-Brasil study.

Blood pressure (BP) is a strong cardiovascular risk factor, predicting cardiovascular mortality in the general population. High salt consumption is a major contributor of increased BP and hypertension. However, there is a controversy on whether BP response to salt intake would be sex-specific. Thus, we aimed to verify the changes in BP according to different salt intake in men and women in a large sample of adults. The present analysis refers to 12 813 participants (from 35 to 64 years) with a validated 12-hour overnight urine collection in which salt intake was estimated. A set of questionnaires, clinical examination, and laboratory tests were carried out during a single visit to one of the six investigation centers involved. Salt intake was 12.9 ± 5.9 g/d in men and 9.3 ± 4.3 g/d in women. BP increases as salt intake increases, regardless of using BP-lowering medication. The slope of increase in BP elicited by salt intake was significantly higher in women than in men. Thus, the increase in BP by salt intake was stepper in women even after controlling for confounders, regardless of using BP-lowering medication or being hypertensive. In conclusion, salt intake is elevated in this large sample of Brazilian adults in which only a few participants are compliant with the recommendation. Also, women have a higher responsiveness of BP according to salt intake than men, and it is not associated with age, BP level, or the use of BP-lowering medication.

Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease.

Background Excessive sodium intake is a risk factor for hypertension, cardiovascular disease and the risk for kidney failure in chronic kidney disease (CKD) patients. Methods We tested the diagnostic performance and the feasibility of an inexpensive method based on urine chloride strips for self-monitoring sodium intake in a series of 72 CKD patients. Results Twenty-four hour urinary chloride as measured by the reactive strips and 24 h urinary sodium were interrelated (r=0.59, p<0.001). Forty-nine out of 72 patients (78%) had a 24 h urinary sodium >100 mmol/24 h, i.e. the upper limit recommended by current CKD guidelines. The strip method had 75.5% sensitivity and 82.6% specificity to correctly classify patients with urine sodium >100 mmol/24 h. The positive and the negative predictive values were 90.2% and 61.3%, respectively. The overall accuracy (ROC curve analysis) of urine chloride self-measurement for the >100 mmol/24 h sodium threshold was 87% (95% CI: 77%-97%). The large majority of patients (97%) perceived the test as useful to help compliance with the prescribed dietary sodium and considered the test as simple and of immediate application (58%) or feasible but requiring attention (39%). Conclusions A simple and inexpensive test for urine chloride measurement has a fairly good performance for the diagnosis of excessive sodium intake. The test is feasible and it is perceived by CKD patients as helpful for enhancing compliance to the dietary sodium recommendations. The usefulness of this test for improving hypertension control in CKD patients will be tested in a clinical trial (Clinicaltrials.gov RF-2010-2314890).

Sodium intake and blood pressure in children with clinical conditions: A systematic review with meta-analysis.

Little is known on the effect of sodium intake on BP of children with clinical conditions. Our objective was therefore to review systematically studies that have assessed the association between sodium intake and BP in children with various clinical conditions. A systematic search of several databases was conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies assessing the association between sodium intake and BP and involving children or adolescents between 0 and 18 years of age with any clinical condition were included. Out of the 6861 records identified, 51 full texts were reviewed, and 16 studies (10 experimental and 6 observational), involving overall 2902 children and adolescents, were included. Ten studies were conducted in children with elevated BP without identifiable cause, two in children with familial hypertension, one in children with at least one cardiovascular risk factor, one in children with chronic renal insufficiency, one in children with urolithiasis, and one in premature infants. A positive association between sodium intake and BP was found in all studies, except one. The meta-analysis of six studies among children with elevated BP without identifiable cause revealed a difference of 6.3 mm Hg (95% CI 2.9-9.6) and 3.5 mm Hg (95% CI 1.2-5.7) in systolic and diastolic BP, respectively, for every additional gram of sodium intake per day. In conclusion, our results indicate that the BP response to salt is greater in children with clinical conditions, mainly hypertension, than in those without associated clinical conditions.

High sodium intake increases blood pressure and risk of kidney disease. From the Science of Salt: A regularly updated systematic review of salt and health outcomes (August 2016 to March 2017).

The purpose of this review was to identify, summarize, and critically appraise studies on dietary salt and health outcomes that were published from August 2016 to March 2017. The search strategy was adapted from a previous systematic review on dietary salt and health. Studies that meet standards for methodological quality criteria and eligible health outcomes are reported in detailed critical appraisals. Overall, 47 studies were identified and are summarized in this review. Two studies assessed all-cause or disease-specific mortality outcomes, eight studies assessed morbidity reduction-related outcomes, three studies assessed outcomes related to symptoms/quality of life/functional status, 25 studies assessed blood pressure (BP) outcomes and other clinically relevant surrogate outcomes, and nine studies assessed physiologic surrogate outcomes. Eight of these studies met the criteria for outcomes and methodological quality and underwent detailed critical appraisals and commentary. Five of these studies found adverse effects of salt intake on health outcomes (BP; death due to kidney disease and initiation of dialysis; total kidney volume and composite of kidney function; composite of cardiovascular disease (CVD) events including, and risk of mortality); one study reported the benefits of salt restriction in chronic BP and two studies reported neutral results (BP and risk of CKD). Overall, these articles confirm the negative effects of excessive sodium intake on health outcomes.

Diuretic state affects ascending thin limb tight junctions.

The nephron segments in the inner medulla are part of the urine concentrating mechanism. Depending on the diuretic state, they are facing a large range of extracellular osmolality. We investigated whether water homeostasis affects tubular transport and permeability properties in inner medullary descending thin limb (IMdTL) and ascending thin limb (IMaTL). Three experimental groups of rats under different diuretic states were investigated on metabolic cages: waterload, furosemide-induced diuresis, and control (antidiuresis). Urine production and osmolalities reflected the 3-day treatment. To functionally investigate tubular epithelial properties, we performed experiments in freshly isolated inner medullary thin limbs from these animals. Tubular segments were acutely dissected and investigated for trans- and paracellular properties by in vitro perfusion and electrophysiological analysis. IMdTL and IMaTL were distinguished by morphological criteria. We confirmed absence of transepithelial electrogenic transport in thin limbs. Although diffusion potential measurements showed no differences between treatments in IMdTLs, we observed increased paracellular cation selectivity under waterload in IMaTLs. NaCl diffusion potential was -5.64 ± 1.93 mV under waterload, -1.99 ± 1.72 mV under furosemide-induced diuresis, and 0.27 ± 0.40 mV under control. The corresponding permeability ratio PNa/Cl was 1.53 ± 0.21 (waterload), 1.22 ± 0.18 (furosemide-induced diuresis), and 0.99 ± 0.02 (control), respectively. Claudins are main constituents of the tight junction responsible for paracellular selectivity; however, immunofluorescence did not show qualitative differences in claudin 4, 10, and 16 localization. Our results show that IMaTLs change tight junction properties in response to diuretic state to allow adaptation of NaCl reabsorption.

Excreción urinaria de iodo y sal en población de Buenos Aires, Argentina / Iodine and salt urinary excretion in Buenos Aires population, Argentina / Excreção urinária de iodo e sal na população de Buenos Aires, Argentina

El iodo es un micronutriente esencial escaso en la dieta. Su deficiencia se asocia con bocio y deterioro cognitivo, entre otras manifestaciones. Desde 1967, la sal de mesa es enriquecida en 33 μg de iodo/g de sal. Recientemente, bajo la propuesta "Menos sal, más vida" se ha legislado para reducir la ingesta de los habituales 10-12 g a 5 g de sal por día. Resulta de interés determinar si la ingesta de sal y la de iodo han disminuido y si están relacionadas. Se evaluó la ingesta reciente de iodo y de sal a través de su excreción urinaria (Reacción de Sandel-Kolthoff y de Mohr, respectivamente), en 514 muestras de orina, agrupadas por sexo y grupo etáreo (<20 años, 20-30 años, 30-60 años y >60 años). Se emplearon los criterios recomendados por la OMS para el análisis de los resultados. La mediana en la excreción de iodo para adultos fue 83 μg/L a la vez que el 18% de las muestras presentaron concentraciones de iodo urinario menores de 50 μg/L, valores indicativos de ingesta deficiente. Un muy bajo porcentaje de muestras (3%) mostró valores de iodo urinario excesivos. El promedio de valores urinarios de sal en adultos fue 5,0 g/L. La correlación global entre ambos parámetros fue de 0,76, pero se encontró un valor más alto de correlación dentro de algunos grupos etarios (hasta 0,91).

Iodine is an essential micro-nutrient in the diet. Its deficiency is associated with goiter and cognitive impairment, among other manifestations. Since 1967, salt has been enriched in 33 μg of iodine/g of salt. Recently, under the proposed "Less salt, more life" regulations tend to reduce the daily salt intake from the usual 10-12 g to 5 g. The aim of this study was to determine if salt, and therefore iodine intakes have declined and whether they are related or not. Recent iodine and salt intakes were assessed through urinary excretion (Sandel-Kolthoff reaction and Mohr method respectively), in 514 urine samples, grouped by sex and age range (<20 years, 20-30 years, 30-60 years y >60 years). The criteria recommended by WHO were used to analyze the results. Medium excretion of iodine for adults was 83 ug/L and 18% of the samples presented urinary iodine concentrations lower than 50 μg/L, indicative of poor iodine intake. A very low percentage of samples (3%) showed excessive urinary iodine values. Medium urinary salt values in adults were 5.0 g/L. The global correlation between both parameters, resulted 0.76, but better correlation was found for some age groups (up to 0.91).

O iodo é um micronutriente essencial escasso na dieta. Sua deficiência está associada com bócio e deterioração cognitiva, entre outras manifestações. Desde 1967, o sal é enriquecido em 33 μg de iodo/g de sal. Recentemente sob a proposta "Menos sal, mais vida" legislou-se para reduzir a ingestão de sal dos habituais 10-12 g para 5 g por dia. É de interesse para determinar se a ingestão de sal e a de iodo diminuíram e se estão relacionados. A ingestão recente de iodo e sal foi avaliada através da excreção urinária (Reação de Sandel-Kolthoff e Mohr respectivamente), em 514 amostras de urina, agrupadas por sexo e idade (<20 anos, 20-30 anos, 30-60 anos e>60 anos). Foram utilizados os critérios recomendados pela OMS para a análise dos resultados. A mediana na excreção de iodo para adultos foi 83 ug/L ao mesmo tempo que 18% das amostras apresentaram concentrações de iodo urinário menores de 50 μg/L, valores indicativos da ingestão deficiente. Uma percentagem muito baixa de amostras (3%) mostrou valores de iodo urinário excessivos. A média de valores de sal urinários em adultos foram 5.0 g/l. A correlação global entre os dois parâmetros foi de 0,76, mas se encontrou um valor mais alto de correlação dentro de alguns grupos etários (até 0,91).

Alteration of Tight Junction Protein Expression in Dahl Salt-Sensitive Rat Kidney.

BACKGROUND/AIMS: Altered pressure natriuresis is an important mechanism of hypertension, but it remains elusive at the molecular level. We hypothesized that in the kidney, tight junctions (TJs) may have a role in pressure natriuresis because paracellular NaCl transport affects interstitial hydrostatic pressure. METHODS: To assess the association of salt-sensitive hypertension with altered renal TJ protein expression, Dahl salt-sensitive (SS) and salt-resistant (SR) rats were put on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood pressure (SBP) and urine NaCl excretion were measured weekly, and kidneys were harvested for immunoblotting and quantitative PCR analysis at the end of the animal experiments. RESULTS: SBP was significantly higher in SS rats than in SR rats during the first to fourth weeks of the animal experiments. During the first and second week, urinary NaCl excretion was significantly lower in SS rats as compared with SR rats. However, the difference between the two groups vanished at the third and fourth weeks. In the kidney, claudin-4 protein and mRNA were significantly increased in SS rats as compared with SR rats. On the other hand, occludin protein and mRNA were significantly decreased in SS rats as compared with SR rats. The expression of claudin-2, claudin-7, and claudin-8 did not vary significantly between the two groups. CONCLUSIONS: In SS rats, SS hypertension was associated with differential changes in renal TJ protein expression. Both upregulation of claudin-4 and downregulation of occludin might increase paracellular NaCl transport in the kidney, resulting in impaired pressure natriuresis in SS rats.

Treatment of Disorders of Sodium Balance in Chronic Kidney Disease.

Extracellular fluid volume expansion is nearly universal in patients with CKD. Such volume expansion has features similar to the syndrome of heart failure with preserved ejection fraction, which not only leads to symptoms but can also lead to further organ damage. Unique treatment challenges are present in this patient population, including low glomerular filtration, which limits sodium chloride filtration, intrinsic tubule predisposition to sodium chloride retention, and proteinuria. In addition, pharmacokinetic considerations alter the disposition of diuretics in patients with CKD and nephrotic syndrome. Maintaining extracellular fluid volume near to normal is often necessary for hypertension treatment in this population, but it may also help prevent progressive cardiovascular and kidney damage. Although powerful diuretics can often accomplish this goal, this often comes at a cost of competing adverse effects. An approach to reduce extracellular fluid volume while avoiding adverse effects, therefore, requires a nuanced yet aggressive therapeutic approach.

The Science of Salt: A regularly updated systematic review of the implementation of salt reduction interventions (September 2016-February 2017).

This periodic review aims to identify, summarize, and appraise studies relating to the implementation of salt reduction strategies that were published between September 2016 and February 2017. A total of 41 studies were included as relevant to the design, assessment, and implementation of salt reduction strategies, and a detailed appraisal was conducted on the seven studies that evaluated the impact of salt reduction strategies. Of these, three were national studies or included large populations and four were conducted in communities with small participant sample sizes. Each study used a different strategy for reducing salt intake varying from category-specific sodium targets for packaged food to use of a low-sodium salt substitute to behavior change interventions. Four studies found statistically significant decreases in dietary salt intake and one study showed statistically significant decreases in mean sodium density of packaged food products. Four of the seven studies used either spot or 24-hour urine samples to measure dietary salt intake and five were conducted in East or Southeast Asia-two of which were in low- and middle-income countries. Study quality varied among the seven studies and all except one had one or more risks related to bias.

The SONG (Salt intake and OrigiN from General foods) Study - A Large-scale Survey of the Eating Habits and Dietary Salt Intake in the Working-age Population.

Objective Dietary salt reduction is important for the prevention and treatment of lifestyle-related diseases, including hypertension. Thus, in order to follow a strict low-salt diet, it is necessary to assess one's salt intake and to become aware of the importance of salt reduction. Methods More than 2,000 employees of a company, who received a periodic health checkup, participated in the present study. They assessed their day-to-day diet-related lifestyle, using the Salt Check Sheet, and we analyzed the correlations among the Salt Check Sheet scores, the daily salt intake (as estimated by a spot urine sample), and the results of the periodic health checkup. Results In the overall survey population, we only found a weak correlation between the salt check scores and the salt intake. In a subgroup analysis, significant correlations between these two variables were observed among untreated hypertensive participants, but not among treated hypertensive participants. We examined the association between 13 individual questionnaire items and the estimated daily salt intake using a multivariate linear regression model and found that only 5 of the 13 questionnaire items were correlated with the daily salt intake. Conclusion We found that a Salt Check Sheet composed of the 5 items that showed a strong correlation with the salt intake might be more useful for periodic health checks of the working-age population.

Seasonal Variation in the Daily Urinary Sodium Excretion in Outpatients from the Morioka Region of Northern Japan.

Objective Although the daily urinary sodium excretion (UNaV) is considered to provide the most reliable estimate of the daily sodium intake, it may be affected by salt loss due to sweating in summer. However, the seasonal variation in the daily UNaV associated with a normal lifestyle is unknown. Methods This study was performed in 348 outpatients from the Morioka region during three seasons: summer (summer 1), winter, and the following summer (summer 2). The daily UNaV (g salt/day) was estimated by the second morning urine method three times during each season. Seasonal variation was defined as a significant trend across the three seasons together with a significant difference between winter and both summers. Results In women, the daily UNaV was higher in winter (11.8±3.0 g salt/day) than in summer 1 (11.2±2.9 g salt/day) or summer 2 (11.0±2.9 g salt/day). In contrast, there was no marked seasonal variation in men. An analysis stratified by age (4 quartiles) identified seasonal variation in the older 2 quartiles of women (aged ≥68 years). In these women, the mean seasonal difference in the daily UNaV was 0.9 g of salt/day for both winter vs. summer 1 and winter vs. summer 2, while it was 0.1-0.8 g of salt/day in the other groups. Conclusion Seasonal variation in the daily UNaV only occurred in older female patients and was relatively small. This is evidence for restricting salt intake throughout the year and should reassure patients who are anxious about salt loss due to sweating in summer.