Urine sodium to urine creatinine ratio as a marker of total body sodium in infants with intestinal failure.

PURPOSE: Urine sodium (UNa) is a measure of total body sodium in infants with intestinal failure (IF) but can be misleading as it does not reflect volume status. Urine sodium to urine creatinine ratio (UNa:UCr) may offer a more accurate measure, but is not routinely used. This study compares UNa:UCr to UNa as a maker of sodium status in infants with IF. METHODS: A retrospective review of infants with IF, from a single center, from 2018 to 2020 was conducted (REB H20-00,816). IF etiology, intestinal anatomy, nutritional intake, urine electrolytes and anthropometrics were collected. Linear mixed effects models adjusting for repeated measures were used to associate UNa and UNa:UCr with weight gain and sodium intake. RESULTS: Twenty-two infants with a median gestational age of 31 weeks were included. IF etiology included gastroschisis (41%), necrotizing enterocolitis (23%), and intestinal perforation (14%). Infants had an average of 3 paired UNa and UNa:UCr measures for a total of 74 paired measurements. UNa:UCr more strongly correlated with sodium intake compared to UNa (R = 0.25, p = 0.032 vs. R = 0.10, p = 0.38). Overall, neither UNa (p = 0.21) nor UNa:UCr (p = 0.16) were significantly correlated with weight gain. However, for infants receiving ≤50% nutrition enterally, weight gain correlated with UNa (p = 0.01) and UNa:UCr (p = 0.01). UNa:UCr >35 predicted adequate growth regardless of enteral intake (92% sensitivity, 59% specificity). CONCLUSION: UNa:UCr is a measure of total body sodium that correlates with sodium intake in infants with IF. Our study indicates UNa:UCr >35 is associated with adequate growth and can be used to guide further validation studies.

Sodium Intake and Proteinuria/Albuminuria in the Population-Observational, Cross-Sectional Study.

Sodium effects on proteinuria are debated. This observational, cross-sectional, population-based study investigated relationships to proteinuria and albuminuria of sodium intake assessed as urinary sodium/creatinine ratio (NaCR). In 482 men and 454 women aged 35-94 years from the Moli-sani study, data were collected for the following: urinary NaCR (independent variable); urinary total proteins/creatinine ratio (PCR, mg/g), urinary albumin/creatinine ratio (ACR, mg/g), and urinary non-albumin-proteins/creatinine ratio (calculated as PCR minus ACR) (dependent variables). High values were defined as PCR ≥ 150 mg/g, ACR ≥ 30 mg/g, and urinary non-albumin-proteins/creatinine ratio ≥ 120 mg/g. Urinary variables were measured in first-void morning urine. Skewed variables were log-transformed in analyses. The covariates list included sex, age, energy intake, body mass index, waist/hip ratio, estimated urinary creatinine excretion, smoking, systolic pressure, diastolic pressure, diabetes, history of cardiovascular disease, reported treatment with antihypertensive drug, inhibitor or blocker of the renin-angiotensin system, diuretic, and log-transformed data of total physical activity, leisure physical activity, alcohol intake, and urinary ratios of urea nitrogen, potassium, and phosphorus to creatinine. In multivariable linear regression, standardized beta coefficients of urinary NaCR were positive with PCR (women and men = 0.280 and 0.242, 95% confidence interval = 0.17/0.39 and 0.13/0.35, p < 0.001), ACR (0.310 and 0.265, 0.20/0.42 and 0.16/0.38, p < 0.001), and urinary non-albumin-proteins/creatinine ratio (0.247 and 0.209, 0.14/0.36 and 0.09/0.33, p < 0.001). In multivariable logistic regression, higher quintile of urinary NaCR associated with odds ratio of 1.81 for high PCR (1.55/2.12, p < 0.001), 0.51 of 1.62 for high ACR (1.35/1.95, p < 0.001), and of 1.84 for high urinary non-albumin proteins/creatinine ratio (1.58/2.16, p < 0.001). Findings were consistent in subgroups. Data indicate independent positive associations of an index of sodium intake with proteinuria and albuminuria in the population.

Parental educational status independently predicts the risk of prevalent hypertension in young adults.

Identification of individuals at risk of hypertension development based on socio-economic status have been inconclusive, due to variable definitions of low socio-economic status. We investigated whether educational status of individuals or their parents predicts prevalent hypertension in young adult population, by analyzing data of more than 37,000 non-institutionalized subjects from Korea National Health and Nutrition Examination Survey 2008 to 2017. Although low educational status of individual subjects was robustly associated with elevation of systolic blood pressure and increased prevalence of hypertension in general population, its impact on prevalent hypertension differed across age subgroups, and was remarkably attenuated in young adults. Parental educational status was significantly associated with prevalent hypertension in young adults, but not or only marginally in elderly population. Low parental educational status was also associated with high sodium intake in young adults, irrespective of subject's own educational status. These collectively indicate that parental educational status, rather than individual's own educational status, better and independently predicts prevalent hypertension in young adults, and that young adults with low parental educational status are prone to intake more sodium, possibly contributing to the increased risk of hypertension development. We expect that our findings could help define young individuals at risk of high sodium intake and hypertension.

Potassium Intake in India: Opportunity for Mitigating Risks of High-Sodium Diets.

INTRODUCTION: Most Indians are vegetarian or eat very little meat, which could imply high potassium intake. Because a high-potassium diet could counterbalance the adverse health effects of high-sodium intake, this study aimed to describe potassium relative to sodium intake and investigate the relationship between blood pressure and potassium intake relative to sodium intake in rural and urban India. METHODS: Investigators collected 24-hour urines from 1,445 participants in a subset of 2 population-based surveys in North India in 2012-2013. Standardized questionnaires were used to collect information on demography, behaviors (tobacco, alcohol consumption, physical activity, and diet [food frequency and 24-hour recall]), and medical history. After evaluating expected versus measured creatinine excretion, the authors calculated median urine potassium excretion and sodium/potassium ratio, according to sex and urban or rural residence, and estimated least square means for the urine measures by participant demographics and comorbidities, after accounting for caloric intake. Two-year blood pressure follow-up data were available in the urban study, and ANCOVA regression was used to determine the association with urine measures. All the statistical analyses of the data were done in January 2019. RESULTS: Acceptable 24-hour urine collections were available in 1,397 participants (rural, n=730). Median urine potassium excretions were 1,492 (IQR=1,012-2,063) and 975 (615-1,497) mg/day; sodium/potassium ratios met the recommended target of <1 in 2.9% rural and 6.6% urban participants. Rural participants did not have higher potassium or lower (better) sodium/potassium ratios when diagnosed with hypertension or other cardiovascular conditions. Higher potassium excretion was associated with lower blood pressure during follow-up among the urban participants (mean systolic blood pressure, 129 vs 133 mm Hg in highest vs lowest potassium excretion tertiles; p=0.029). CONCLUSIONS: Low potassium intake in India warrants dietary policies promoting intake of potassium-rich foods to improve heart health. This approach may be more acceptable than programs focused on sodium reduction alone.

Effect of Dietary Sodium and Potassium Intake on the Mobilization of Bone Lead among Middle-Aged and Older Men: The Veterans Affairs Normative Aging Study.

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.

Comparison of Urinary Sodium and Blood Pressure Relationship From the Spot Versus 24-Hour Urine Samples.

Background We compared the relationship between sodium (Na) intake and blood pressure when Na intake was estimated from first- and second-morning spot urine samples using the INTERSALT (International Study on Salt and Blood Pressure) formula, versus directly measured 24-hour samples. Methods and Results We collected 24-hour urine and first- and second-morning voids of 383 participants in coastal Bangladesh for 2 visits. We measured participants' blood pressure using an Omron® HEM-907 monitor. To assess the shape of the relationship between urinary Na and blood pressure, we created restricted cubic spline plots adjusted for age, sex, body mass index, smoking and alcohol consumption, physical activities, religion, sleep hours, and household wealth. To assess multicollinearity, we reported variance inflation factors, tolerances, and Leamer's and Klein's statistics following linear regression models. The mean daily urinary Na was 122 (SD 26) mmol/d for the first; 122 (SD 27) mmol/d for the second; and 134 (SD 70) mmol/d for the 24-hour samples. The restricted cubic spline plots illustrated no association between first-morning urinary Na and systolic blood pressure until the 90th percentile distribution followed by a downward relationship; a nonlinear inverse-V-shaped relationship between second-morning urinary Na and systolic blood pressure; and a monotonic upward relationship between 24-hour urinary Na and systolic blood pressure. We found no evidence of multicollinearity for the 24-hour urinary Na model. Conclusions The urinary Na and systolic blood pressure relationship varied for 3 urinary Na measurements. Twenty-four-hour urinary Na captured more variability of Na intake compared with spot urine samples, and its regression models were not affected by multicollinearity.

Sodium Intake Is associated With Endothelial Damage Biomarkers and Metabolic Dysregulation.

BACKGROUND: Mounting evidence has associated high sodium (HS) intake with hypertension, cardiovascular disease, and stroke. We investigated whether HS intake modulates the parameters of endothelial damage, inflammation, and oxidative stress. METHODS: We used a cross-sectional study design including 223 Chilean subjects (6.9-65.0 years old). We measured aldosterone, renin activity, cortisol, cortisone, adiponectin, leptin, hsCRP, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), metalloproteinase (MMP)-9 and MMP-2 activity, and malondialdehyde. Sodium and creatinine were measured in 24-hour urine samples. The subjects were divided by sodium intake, high sodium (HS): ≥150 mEq/day, n = 118, and adequate sodium (AS): <150 mEq/day, n = 105. RESULTS: We observed a positive correlation between urinary sodium excretion and blood pressure (r = 0.1669, P = 0.0124 for systolic and r = 0.2416, P = 0.0003 for diastolic), glycemia (r = 0.2660, P < 0.0001), and triglycerides (r = 0.1604, P = 0.0175) and a highly significant correlation between sodium excretion and PAI-1 (r = 0.2701, P < 0.0001). An inverse correlation was observed between urinary sodium and HDL-cholesterol (r = -0.2093, P = 0.0018) and adiponectin (r = -0.2679, P < 0.0001). In a linear regression model, urinary sodium excretion remained significantly associated with PAI-1 values even after adjusting for age, gender, and BMI. The HS group had higher blood pressure, glycemia, HOMA-IR, atherogenic index of plasma, and PAI-1 values than the group with AS intake. CONCLUSIONS: HS intake is associated with endothelial damage (high PAI-1) and metabolic dysregulation. On the other hand, inflammation and oxidative stress parameters are not modified by sodium intake.

Association between urinary sodium excretion and coronary heart disease in hospitalized elderly patients in China.

Objective This study was performed to evaluate the association between urinary sodium excretion and coronary heart disease (CHD) in hospitalized elderly patients in China. Methods The 24-h urinary excretion specimens of 541 patients were collected, and the serum creatinine concentration and urinary sodium/potassium ratio were measured. Associations were explored by multivariate logistic regression analysis. Results The mean 24-h urinary sodium excretion was 200.4 mmol, corresponding to 11.7 g of salt intake. Both of these values were higher in men than in women. The salt intake of 80- to 89-year-old patients was significantly lower than that of 70- to 79-year-old patients. The 24-h urinary sodium excretion and spot urine Na/K ratios were significantly higher in overweight/obese and hypertensive patients. The 24-h urinary sodium excretion of men who smoked was significantly higher than that of women. The spot urine Na/K ratio was significantly higher in patients with cerebral thrombosis. The urinary Na/K ratio, smoking status, and hypertension were independent risk factors for CHD. Conclusions This cross-sectional survey suggests that the Na/K ratio may better represent salt loading than Na excretion alone in studying the association between sodium intake and CHD. There was no association between sodium and CHD prevalence.

Study design and baseline characteristics of a combined educational and environmental intervention trial to lower sodium intake in Swiss employees.

BACKGROUND: Blood pressure is a primary cardiovascular disease risk factor. Population-wide governmental strategies aim to reduce lifestyle and dietary risk factors for hypertension, one of which is an unbalanced diet with high sodium and low potassium intakes. Nutrition interventions in the workplace are considered a promising approach in encouraging health-promoting behaviors. We developed and conducted the health promoting sodium reduction trial "Healthful & Tasty: Sure!" in worksites in the German-speaking part of Switzerland from May 2015 to Nov 2016, for which we present the study protocol and baseline characteristics. METHODS: Healthful & Tasty, a cluster nonrandomized single-arm trial with calibration arm, aimed to demonstrate the effectiveness of a combined educational and environmental intervention in the workplace in reducing employees' average daily sodium/salt intake by 15%. To this end, health and food literacy of employees and guideline compliance among the catering facility team needed to be improved. The primary outcome measure was sodium/salt intake estimated from sodium excretion in a 24-h urine sample. Secondary outcome measures included changes in the overall qualitative diet composition, blood pressure, anthropometric indices, and health and food literacy. Of eight organizations with catering facilities, seven organizations took part in the nutrition education and catering salt reduction interventions, and one organization participated as a control. Overall, 145 consenting employees were included in the staggered, one-year four-phase trial, of which 132 participated in the intervention group. In addition to catering surveys and food sampling, the trial included five follow-up health assessments including questionnaires, blood pressure measurements, anthropometrics, and sodium, potassium, and iodine intake measurements obtained from 24-h and spot urine samples, and a food record checklist. Exploratory and hypothesis generating baseline statistical analysis included 141 participants with adequate 24-h urine samples. DISCUSSION: Despite practice-driven limitations to the study design and small cluster and participant numbers, this trial has methodological strength and will provide important insights into the effectiveness of a combined educational and environmental intervention to reduce salt intake among female and male Swiss employees. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006790 . Registered 23 September 2014.

Sodium excretion and associated factors in urine samples of African descendants in Alcântara, Brazil: a population based study.

In most countries, salt intake has been excessive and constitutes one of the main risk factors for disease development, especially hypertension. Factors such as age, gender, sedentary lifestyle, smoking, African descent, obesity, dietary habits and family history of hypertension may be associated with high blood pressure. Studies show a positive association between the excretion of sodium and increased blood pressure. We evaluated the urinary excretion of sodium and associated factors in isolated urine samples of African descendants from remaining Quilombos. We performed a cross-sectional, population-based study with 1162 African descendants living in remaining quilombos in Alcântara, Maranhão, Brazil. Demographic, nutritional, clinical and laboratory data were analyzed. Urinary sodium excretion was estimated using the Kawasaki equation. A multivariate linear regression model was used to identify the variables related to sodium excretion. The average age was 37.6 ± 11.8 years and 51.2% were women. The prevalence of hypertension was 21.3%. The average urinary excretion of sodium was high, especially among the hypertensive (217.9 ± 90.1 vs. 199.2 ± 83.0 mmol/d; p = .002). After an adjusted analysis, only the waist circumference (odds ratios (OR) = 1.16; confidence intervals(CI)95%: 1.03-1.30), triglyceride (OR = 1.13; CI95%: 1.05-1.22), systolic blood pressure (OR = 1.19; CI95%: 1.08-1.32) and Chronic Kidney Disease Epidemiology (CKD-EPI;OR = 1.24; CI95%: 1.15-1.35) remained related to urinary sodium excretion. African descendants had a high rate of sodium excretion, especially among those who had hypertension. Abdominal adiposity, triglyceride and systolic blood pressure levels and renal function by CKD-EPI equation were associated to urinary sodium excretion.

Associations between dietary salt, potassium and blood pressure in South African adults: WHO SAGE Wave 2 Salt & Tobacco.

BACKGROUND & AIMS: In June 2016, South Africa implemented legislation mandating maximum sodium levels in a range of processed foods with a goal of reducing population salt intake and disease burden from hypertension. Our aim was to explore the relationship between salt and blood pressure (BP) in a subsample of the World Health Organization Study on global AGEing and adult health (SAGE) Wave 2 before implementation of legislation in South Africa. METHODS & RESULTS: Blood pressure (BP) was measured in triplicate (n = 2722; median age 56 years; 33% male) and 24-h urine collected in a nested subsample (n = 526) for sodium, potassium and creatinine analysis. Hypertension prevalence was 55% in older adults (50-plus years) and 28% in younger adults (18-49 years). Median salt intake (6.8 g/day) was higher in younger than older adults (8.6 g vs 6.1 g/day; p < 0.001), and in urban compared to rural populations (7.0 g vs 6.0 g/day; p = 0.033). Overall, 69% of participants had salt intakes above 5 g/day. Potassium intakes were generally low (median 35 mmol/day) with significantly lower intakes in rural areas and older adults. Overall, 91% of adults failed to meet the daily potassium recommendation of 90 mmol/d. Salt intakes above 5 g/day, and to a greater extent, a dietary sodium-to-potassium (Na:K) ratio above 2 mmol/mmol, were associated with significantly steeper regression slopes of BP with age. CONCLUSION: These preliminary results indicate that high dietary Na:K ratio may lead to a greater increase in BP and hypertension risk with age. Interventions to increase potassium intakes alongside sodium reduction initiatives may be warranted.

Simple questions in salt intake behavior assessment: comparison with urinary sodium excretion in Japanese adults.

BACKGROUND AND OBJECTIVES: To clarify whether six conventional 'high-risk' behaviors toward excess salt intake captured by simple questions such as frequency of salty food consumption are related to actual salt intake. Also, to examine the relationship of nutrition knowledge, food label use, and food preparation with actual salt intake. METHODS AND STUDY DESIGN: Study participants were 742 subjects (370 men and 372 women) aged 20-69 years from 20 areas of Japan. Salt intake and dietary knowledge/behavior were evaluated with two 24-hour urine collections and a questionnaire, respectively. Multivariable linear regression analyses by sex included sodium excretion as a dependent variable, each knowledge/behavior item as an independent variable, and with age, body mass index, education, and smoking as covariates. RESULTS: Four 'high-risk' behaviors (frequency of miso soup and salty foods consumption, proportion of consumed noodle soup, and amount of seasoning/condiment use) were associated with higher sodium excretion in men (p for trend <=0.04) and were marginally associated in women (p for trend <=0.06). Combination of these behaviors elevated the odds ratios for excess salt intake (sodium excretion: >136 mmol/day). Most of the other nine dietary factors were not associated with sodium excretion. Interestingly, women who decided to purchase foods after referring to the salt/sodium content information on food label, had significant lower sodium excretion than other women (p for trend=0.03). CONCLUSIONS: High-risk behaviors toward excess salt intake captured by simple questions were actually related to excess salt intake. Specific and practical advice based on answers to these questions might contribute to salt reduction in Japanese population.

Formula to detect high sodium excretion from spot urine in chronic kidney disease patients / Fórmula para detectar elevada excreção de sódio a partir de amostra isolada de urina de pacientes com doença renal crônica pré-dialítica

Abstract Introduction: Excessive sodium intake is related to adverse renal and cardiovascular outcomes in patients with chronic kidney disease (CKD) and assessment of sodium intake is complex and not evaluated very often in clinical practice. Objective: To develop a new formula to estimate 24h sodium excretion from urine sample (second void) of patients with CKD. Methods: We included 51 participants with CKD who provided 24-hour urine collection and a sample of the second urine of the day to determine the sodium excretion. A formula to estimate the 24-hour sodium excretion was developed from a multivariate regression equation coefficients. The accuracy of the formula was tested by calculating the P30 (proportion of estimates within 30% of measured sodium exection) and the ability of the formula to discriminate sodium intake higher than 3.6 g/day was evaluated by ROC curve. Results: Correlation test between measured and estimated sodium was significant (r = 0.57; p < 0.001), but P30 test identified a low accuracy (61%) of the formula. Different cutoff points were tested by performance tests and a ROC curve was generated with the cutoff that showed better performance (3.6 g/day). An area under the curve of 0.69 with a sensitivity of 0.91 and specificity of 0.53 was obtained. Conclusion: A simple formula with high sensitivity in detecting patients with sodium consumption higher than 3.6 g/day from isolated urine sample was developed. Studies with a higher number of participants and with different populations are necessary to test formula´s validity.

Resumo Introdução: O consumo excessivo de sódio está relacionado a piores desfechos renais e cardiovasculares em pacientes com doença renal crônica (DRC), mas a avaliação deste consumo é complexa e mensurada com baixa frequência na prática clínica. Objetivo: Desenvolver uma nova fórmula para estimar a excreção de sódio de 24h a partir da concentração de sódio em amostra isolada da segunda urina do dia em pacientes com DRC pré-dialítica. Métodos: 51 participantes com DRC forneceram coleta de urina de 24h e uma amostra da segunda urina do dia para determinação da excreção de sódio. Uma fórmula para estimar a excreção de sódio de 24h foi desenvolvida a partir dos coeficientes da equação de regressão. A acurácia da fórmula foi testada por meio do cálculo do P30. A habilidade da fórmula em discriminar consumo de sódio superior a 3,6 g/dia foi avaliada pela curva ROC. Resultados: O teste de correlação entre sódio mensurado e estimado pela fórmula foi r = 0,57; p < 0,001, porém o resultado do P30 identificou baixa acurácia (61%). Diferentes pontos de corte foram testados por meio de testes de performance e uma curva ROC foi gerada com o ponto de corte de melhor performance (3,6 g/dia). Foi obtida uma área sob a curva de 0,69 com sensibilidade 0,91 e especificidade 0,53. Conclusão: Foi desenvolvida uma fórmula simples com elevada sensibilidade em detectar pacientes com consumo de sódio superior a 3,6 g/dia a partir de amostra de urina isolada. Estudos que testem a fórmula com um maior número de participantes e com outras populações são necessários.

Interplay between renal endothelin and purinergic signaling systems.

Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeostasis, will fill a significant knowledge gap and may provide novel antihypertensive treatment options. Therefore, this review focuses on the cross talk between endothelin and purinergic signaling as it relates to the renal regulation of sodium and blood pressure homeostasis.

Early oxytocin inhibition of salt intake after furosemide treatment in rats?

Body fluid homeostasis requires a complex suite of physiological and behavioral processes. Understanding of the role of the central nervous system (CNS) in integrating these processes has been advanced by research employing immunohistochemical techniques to assess responses to a variety of body fluid challenges. Such techniques have revealed sex/estrogen differences in CNS activation in response to hypotension and hypernatremia. In contrast, it has been difficult to conclusively identify specific CNS areas and neurotransmitter systems that are activated by hyponatremia using these techniques. In part, this difficulty is due to the temporal disconnect between the physiological effects of treatments commonly used to deplete body sodium and the behavioral response to such depletion. In some methods, sodium ingestion is delayed in association with increased oxytocin (OT), suggesting an inhibitory role for OT in sodium intake. Urinary sodium loss increases within an hour after treatment with furosemide, a natriuretic-diuretic, but sodium intake is delayed for 18-24h. Accordingly, we hypothesized that acute furosemide-induced sodium loss activates centrally-projecting OT neurons which provide an initial inhibition of sodium intake, and tested this hypothesis in ovariectomized Sprague-Dawley rats with or without estrogen using immunohistochemical methods. Neuronal activation in the hypothalamic paraventricular nuclei (PVN) after administration of furosemide corresponded to the timing of the physiological effects. The activation was not different in estrogen-treated rats, nor did estrogen alter the initial suppression of sodium intake. However, virtually no fos immunoreactive (fos-IR) neurons in the parvocellular PVN were also immunolabeled for OT. Thus, acute sodium loss after furosemide produces neural activation and an early inhibition of sodium intake that does not appear to involve activation of centrally-projecting OT neurons and is not influenced by estrogen.

Sodium and potassium intake estimated using two methods in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) / Consumo de sódio e potássio estimado por dois métodos no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

ABSTRACT CONTEXT AND OBJECTIVE: Sodium and potassium intake from different food sources is an important issue regarding cardiovascular physiology. Epidemiological assessment of the intake of these electrolytes intake is done through food frequency questionnaires or urinary excretion measurements. Our aim was to compare these methods using a sample of Brazilian civil servants. DESIGN AND SETTING: Cross-sectional baseline evaluation from the Brazilian Longitudinal Study of Adult Health. METHODS: Sodium and potassium intake was obtained using two methods: a semi-quantitative questionnaire including 114 food items; and overnight 12-hour urinary excretion measurement. Sodium and potassium estimates obtained through the questionnaire were adjusted for energy intake using the residual method. Urinary excretion measurements were considered valid if they met three adequacy criteria: collection time, volume and total creatinine excretion. Mean nutrients were estimated, and Spearman correlations were calculated. Sodium and potassium intake was categorized into quintiles, and weighted kappa coefficients and percentage agreement were calculated. The significance level for all tests was 0.05. RESULTS: Data from 15,105 participants were analyzed, and significant differences between mean intakes of sodium (questionnaire: 4.5 ± 1.7 g; urine: 4.2 ± 2.1 g) and potassium (questionnaire: 4.7 ± 1.8 g; urine: 2.4 ± 1 g) were found. Weak agreement was found for sodium (K = 0.18) and potassium (K = 0.16). The percentage disagreement between methods ranged from 41.8 to 44.5%, while exact concordance ranged from 22.1% to 23.9%. CONCLUSIONS: The agreement between the food frequency questionnaire and urinary excretion measurements for assessment of sodium and potassium intakes was modest.

RESUMO CONTEXTO E OBJETIVO: O consumo de sódio e potássio de diferentes fontes alimentares é uma questão importante para a fisiologia cardiovascular. A avaliação epidemiológica do consumo desses eletrólitos é feita pelo questionário de frequência alimentar ou pela excreção urinária. O objetivo deste estudo é comparar esses métodos em uma amostra de servidores públicos brasileiros. TIPO DE ESTUDO E LOCAL: Avaliação transversal da linha de base do Estudo Longitudinal de Saúde do Adulto. MÉTODOS: O consumo de sódio e potássio foi obtido por dois métodos: questionário semi-quantitativo com 114 itens alimentares e excreção urinária de 12 horas noturnas. Estimativas de sódio e potássio obtidas pelo questionário foram ajustadas pela energia utilizando o método residual. A excreção urinária foi considerada válida se atendesse a três critérios: tempo de coleta, volume e excreção total de creatinina adequados. Foram estimadas médias dos nutrientes e calculada a correlação de Spearman. O consumo de sódio e potássio foi categorizado em quintis e foram calculados o kappa ponderado e o percentual de concordância. O nível de significância para todos os testes foi de 0,05. RESULTADOS: Foram analisados dados de 15,105 participantes e encontradas diferenças significativas entre médias de sódio (questionário: 4,5 ± 1,7 g; urina: 4,2 ± 2,1 g) e potássio (questionário: 4,7 ± 1,8 g; urina: 2,4 ± 1 g). Foi encontrada fraca concordância para sódio (K = 0,18) e potássio (K = 0,16). Percentuais de discordância entre métodos variaram de 41,8-44,5%; concordâncias exatas de 22,1-23,9%. CONCLUSÃO: A concordância entre o questionário de frequência alimentar e excreção urinária para avaliação do consumo de sódio e potássio foi modesta.

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake.

BACKGROUND AND OBJECTIVES: Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Baseline plasma 25(OH)D and 1,25(OH)2D were measured by liquid chromatography tandem mass spectrometry, and sodium intake was assessed by 24-hour urine collections in the general population-based Prevention of Renal and Vascular End-Stage Disease cohort (n=5051). Two primary outcomes were development of urinary albumin excretion >30 mg/24 h and eGFR (creatinine/cystatin C-based CKD Epidemiology Collaboration) <60 ml/min per 1.73 m(2). Participants with CKD at baseline were excluded. In Cox regression analyses, we assessed associations of vitamin D with developing increased albuminuria or reduced eGFR and potential interaction with sodium intake. RESULTS: During a median follow-up of 10.4 (6.2-11.4) years, 641 (13%) participants developed increased albuminuria, and 268 (5%) participants developed reduced eGFR. Plasma 25(OH)D was inversely associated with increased albuminuria (fully adjusted hazard ratio [HR] per SD higher, 0.86; 95% confidence interval [95% CI], 0.78 to 0.95; P=0.003) but not reduced eGFR (HR, 0.99; 95% CI, 0.87 to 1.12; P=0.85). There was interaction between 25(OH)D and sodium intake for risk of developing increased albuminuria (P interaction =0.03). In participants with high sodium intake, risk of developing increased albuminuria was inversely associated with 25(OH)D (lowest versus highest quartile: adjusted HR, 1.81; 95% CI, 1.20 to 2.73, P<0.01), whereas this association was nonsignificant in participants with low sodium intake (HR, 1.29; 95% CI, 0.94 to 1.77; P=0.12). Plasma 1,25(OH)2D was not significantly associated with increased albuminuria or reduced eGFR. CONCLUSIONS: Low plasma 25(OH)D is associated with higher risk of developing increased albuminuria, particularly in individuals with high sodium intake, but not of developing reduced eGFR. Plasma 1,25(OH)2D is not associated with risk of developing increased albuminuria or reduced eGFR.

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population.

BACKGROUND: Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. METHODS AND RESULTS: We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. CONCLUSIONS: Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population.

LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone.

BACKGROUND: LCZ696, an angiotensin receptor-neprilysin inhibitor, has recently been demonstrated to exert more beneficial effects on hypertensive or heart failure patients than conventional renin-angiotensin system blockers. However, the mechanism underlying the benefit of LCZ696 remains to be understood. The present study was undertaken to examine the effect of LCZ696 compared with valsartan on hypertension and cardiovascular injury. METHODS: (i) Using telemetry, we compared the hypotensive effect of LCZ696 and valsartan in spontaneously hypertensive rats (SHR) that were fed a high-salt diet followed by a low-salt diet. (ii) We also examined the comparative effect of LCZ696 and valsartan on salt loaded SHRcp, a model of metabolic syndrome. RESULTS: (i) LCZ696 exerted a greater blood pressure (BP) lowering effect than valsartan in SHR regardless of high-salt or low-salt intake. Additive BP reduction by LCZ696 was associated with a significant increase in urinary sodium excretion and sympathetic activity suppression. (ii) LCZ696 significantly ameliorated cardiac hypertrophy and inflammation, coronary arterial remodeling, and vascular endothelial dysfunction in high-salt loaded SHRcp compared with valsartan. CONCLUSIONS: LCZ696 caused greater BP reduction than valsartan in SHR regardless of the degree of salt intake, which was associated with a significant enhancement in urinary sodium excretion and sympathetic activity suppression. Furthermore, an additive BP lowering effect of LCZ696 led to greater cardiovascular protection in hypertensive rats.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass.

BACKGROUND/OBJECTIVES: High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. SUBJECTS/METHODS: A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. RESULTS: Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. CONCLUSIONS: High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.