Low Sodium Group Research Articles

Abstract P397: Effects of Dietary Sodium Reduction on Systemic Inflammation: Findings from DASH-Sodium Study

Background: High sodium intake is a significant risk factor for hypertension and cardiovascular disease. Animal studies have demonstrated that high salt diet promotes tissue inflammation and increases systemic inflammation, such that it is plausible that sodium induced inflammation might be another pathway to hypertension. However, whether the link between dietary sodium intake and systematic inflammation in humans remains unclear due to limited human studies, different designs and inconsistent findings. Therefore, we tested the hypothesis that dietary sodium reduction reduces systemic inflammation in humans by leveraging the randomized controlled trial design of the DASH-Sodium study. Methods: DASH-Sodium study was a multicenter, randomized trial comparing the effects on blood pressure (BP) of three levels of sodium intake (3450 mg/d, 2300mg/d, and 1150 mg/d) in two diets (DASH vs American) among US adults. Five systematic inflammatory markers including hs-CRP, IFN-γ, IL-6, IL-10, and TNF-α were measured at each study visit in stored plasma samples from 224 participants. Two-level mixed-effects linear regression models were used to assess the effect of sodium reduction on inflammatory markers with adjustment of covariates. Results: A total of 224 participants (aged 49.4±9.5 yrs, 61% female, 62% black, and 2% other races) from the DASH-Sodium study were included in the analyses. Overall, compared to high sodium group, low sodium group had slightly elevated hs-CRP ( p =0.013), and intermediate sodium group had decreased TNF-α ( p =0.011). Both significances, however, disappeared after adjusting for multiple testing ( p adjust >0.01). Conclusion: Modest dietary sodium reduction as recommended did not induce significant changes in systematic inflammation in humans.

Calcium- and Sodium-Rich Food Intake among Koreans with and without Metabolic Syndrome: Cross-Sectional Analysis of the Korean Genome and Epidemiology Study.

The prevalence of metabolic syndrome (MetS) is increasing. While calcium and sodium are known nutritional factors used for managing MetS, few studies have focused on food-based analyses. This cross-sectional study examined the distribution of calcium- and sodium-rich food intake among Koreans with MetS. This cross-sectional analysis evaluated 130,423 participants from the Health Examinees-Gem cohort study. Foods contributing up to 90% of the calcium and sodium intake were selected from the semi-quantitative food frequency questionnaire, and consumption levels were calculated. MetS was defined as satisfying three or more criteria from the National Cholesterol Education Program Adult Treatment Panel III. The results are presented as odds ratios (OR) with an interquartile range (ORIQR) and 95% confidence interval. Participants with MetS showed a low calcium intake (ORIQR = 0.95 and 0.92 for men and women, respectively), low consumption of dairy products (ORIQR = 0.92 and 0.89), beverages except for coffee or green tea (ORIQR = 0.97 and 0.96), and bread (ORIQR = 0.96 and 0.94). Men with MetS consumed high total sodium (ORIQR = 1.04), and large amounts of Kimchi (ORIQR = 1.03), fermented paste (ORIQR = 1.04), and noodles (ORIQR = 1.07). Women with MetS consumed more Kimchi than those without MetS (ORIQR = 1.04). The odds ratio for the low calcium and high sodium group compared to the high calcium and low sodium group was 1.26. The MetS group consumed less calcium-rich foods and more sodium-rich foods than those without MetS. Patients with MetS might benefit from precise recommendations of high calcium-rich and low sodium-rich foods.

Effect of Salt Substitution on Ambulatory Blood Pressure, Kidney Function and Inflammation in Middle-Aged and Elderly Hypertensive Patients.

Low-sodium (LS) salt substitution is recognized for its potential to reduce blood pressure (BP), but most research relies on office BP measurement (OBPM). There is a lack of data on salt substitution's effect on target organs, such as the kidney as measured by the urine albumin-to-creatinine ratio (UACR), and its impact on inflammatory cytokines, particularly high-sensitivity C-reactive protein (hs-CRP). To evaluate the effect of LS salt substitution on ambulatory BP measurement (ABPM), kidney function, and inflammation in middle-aged and elderly hypertensive patients. In this 12-month prospective, multi-center, randomized, double-blind study, 352 hypertensive patients were randomly assigned to the normal salt (NS) group (n = 176) or the LS group (n = 176) at a 1:1 ratio. ABPM, fasting blood, and morning first spot urine samples were obtained at baseline and the endpoint. Of the 352 patients, 322 completed all follow-up surveys, and 301 underwent ABPM. In the LS roup, significant reductions were observed in 24-hr systolic BP (-2.3 mmHg), 24-hr diastolic BP (-1.5 mmHg), daytime systolic BP (-2.6 mmHg), daytime diastolic BP (-1 mmHg), and nighttime systolic BP (-0.1 mmHg) compared to the NS group (all p 0.05). However, the change in nighttime diastolic BP was not statistically significant (-0.3 vs. 1.1 mmHg, p = 0.063). Additionally, the LS group showed a more substantial decrease in UACR (-2.05 vs. -7.40 µg/mg, p = 0.004) and hs-CRP (-0.06 vs. -0.24 mg/L, p = 0.048) compared to NS. LS salt substitution significantly decreased ABPM, suggesting a notable impact on hypertension. Furthermore, it demonstrated a protective impact on kidney function, as evidenced by changes in UACR. Additionally, LS salt substitution appeared to reduce inflammation, indicated by the decrease in hs-CRP levels. The study was registered in the Chinese clinical trial registry (registration number: ChiCTR1800019727).

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

Lipidomics reveals the relationship between lipid oxidation and flavor formation of basic amnio acids participated Low-Sodium cured large yellow croaker.

The effects of basic amino acids on lipid oxidation and the formation of volatile compound in low-sodium cured large yellow croaker were investigated. Basic amino acids contribute a lot in inhibiting the degradation of phospholipids, especially l-lysine. Lipid oxidation was also inhibited by basic amino acids, and the total oxidation of groups could be sorted as low-sodium (LS)>control (C)>l-Histidine participated LS group (LS-His)>l-Arginine participated LS group (LS-Arg)>l-lysine participated LS group (LS-Lys). PC 18:1/20:5, PC 16:0/18:1, triacylglycerol (TG) 16:1/20:5/22:6, etc., were found to be key differential lipid metabolites, and 1-propanol, 2-methyl, gamma-hexalactone, etc. were recognized as key differential volatile compounds. The results of correlation analysis showed that alcohols and esters were positively correlated with TG molecules composed of saturated fatty acids and monounsaturated fatty acids. These findings provided new insights into the relationship between flavor formation and the degradation and oxidation of lipids.

Effect of Low and High Sodium Dialysate on Functional Capacity and Health Related Quality of Life in Hemodialysis Patients

Abstract Background Patients on dialysis have low health related quality of life (HRQOL) and an annual mortality rate many-fold greater than the general population. There is uncertainty about whether low sodium in dialysis fluid improves overall health and wellbeing for people on haemodialysis, since there are mixtures of probably good and bad effects. Aim To assess the effect of low sodium and high sodium dialysate on functional capacity and HRQOL in hemodialysis patients. Patients and Methods comparative case-control study conducted on 60 ESRD patients on maintenance hemodialysis receiving their treatment at the Nephrology hemodialysis unit in Luxor International Hospital from June 2021 till November 2021. The study population was divided into 2 groups: Group 1: included 30 patients on low sodium dialysate (130 mmol/l). Group 2: included 30 patients on high sodium dialysate (138 mmol/l). Results Our data revealed a significant increase in the percentage of hypertensive patients recruited to be among the low sodium dialysate group as compared with high sodium group (P value &amp;lt;0.001). At the end of the study, there were a significant decrease in DBP, IDWG and UF among low sodium group compared with high sodium group, there were a significant increase in 6MWT and SF-36 in Low sodium group when compared with High sodium group. No statistical significant difference between the studied groups as regard each of the laboratory data, ECG, and ECHO at the end of the study (P value&amp;gt;0 Conclusion Low sodium dialysate is effective in improving the health related quality of life of hypertensive hemodialysis patients, however, it did not reduce left ventricular mass relative to control despite improving fluid status.

Effect of low-sodium compound salt on the taste and volatile flavor of salt-baked chicken

This research was conducted to analyze the effect of low-sodium compound salt (LCS) on the flavor of salt-baked chicken (SBC) by employing instrumental analysis and sensory evaluation. The results illustrated that LCS enhanced the volatile flavor and taste of SBC, predominantly its umami taste. The content of free amino acids, low-molecular-weight water-soluble peptides, fatty acids, and taste nucleotides was higher in the low-sodium group (LS group). The work exhibited that the LS group was comparatively abundant in the variants and the contents of typical volatile flavor compounds, namely, benzaldehyde, 2-butanone, and 1-octen-3-ol. The sensory evaluator was unable to distinguish any substantial variations between different groups of SBC. The results concluded that SBC, albeit composed of LCS, is efficacious in sustaining an enhanced flavor. The findings could constitute a theoretical basis for formulating innovative low-sodium sauce-stewed products and for establishing flavor profiles in low-sodium meat products.

Renal transplant hastalarında idrar sodyum atılımının metabolik sendrom, hipertansiyon ve greft fonksiyonu ile ilişkisinin değerlendirilmesi

Aim: To evaluate the relationship between high sodium intake determined by spot urinary sodium excretion with metabolic syndrome, hypertension, and graft function in renal transplant (RT) recipients.&#x0D; Materials and methods: 152 RT recipients were enrolled. The demographic characteristics, office blood pressure (BP) values, height, weight, body mass index, waist and hip measurements, immunesuppressive drugs, other medications and biochemical parameters of the patients were recorded. Spot urinary sodium and spot urinary protein excretions were measured in the first morning urine in all the RT recipients. The patients were grouped as low sodium excretion (≤57) and high sodium excretion (≥58) based on the median value of 57 in spot urinary sodium.&#x0D; Results: In the low sodium group; creatinine values were found to be significantly lower (p

Analysis and identification of ancient glass components based on qualitative-quantitative data mining

First of all, the data is visualized by grouping the data in the form and drawing a scatter diagram. By observing the distribution of the data in the scatter plot, the classification indexes of high-potassium glass and lead-barium glass were found. Secondly, the Spearman coefficient is used to test these classification indicators. The results show that the constructed classification system is more accurate, the Spearman coefficient is small, and the fitting effect is excellent. Secondly, through the combination of qualitative and quantitative methods, the cultural relics sub-category classification index was double screened, and the chemical composition of the sub-category classification index was determined by combining the law analyzed from the scatter plot and the index weight solved by the entropy weight method. Then, the high-potassium glass was divided into low-calcium and low-copper group and high-calcium and high-copper group by K-means method. The glass was divided into high copper group, low sodium and high calcium group and high sodium and low calcium group. Finally, all the unknown types of cultural relics in the table are divided into subclasses, and the sensitivity and rationality of the classification system of major classes and subclasses are tested one by one by fitting the known data and calculating the contour coefficient. It is concluded that the classification system has a good fit to the data.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial

Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events. SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand). Eligible patients were aged 18 years or older, with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned (1:1), using a standard number generator and varying block sizes of two, four, or six, stratified by site, to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT02012179, and is closed to accrual. Between March 24, 2014, and Dec 9, 2020, 806 patients were randomly assigned to a low sodium diet (n=397) or usual care (n=409). Median age was 67 years (IQR 58-74) and 268 (33%) were women and 538 (66%) were men. Between baseline and 12 months, the median sodium intake decreased from 2286 mg/day (IQR 1653-3005) to 1658 mg/day (1301-2189) in the low sodium group and from 2119 mg/day (1673-2804) to 2073 mg/day (1541-2900) in the usual care group. By 12 months, events comprising the primary outcome had occurred in 60 (15%) of 397 patients in the low sodium diet group and 70 (17%) of 409 in the usual care group (hazard ratio [HR] 0·89 [95% CI 0·63-1·26]; p=0·53). All-cause death occurred in 22 (6%) patients in the low sodium diet group and 17 (4%) in the usual care group (HR 1·38 [0·73-2·60]; p=0·32), cardiovascular-related hospitalisation occurred in 40 (10%) patients in the low sodium diet group and 51 (12%) patients in the usual care group (HR 0·82 [0·54-1·24]; p=0·36), and cardiovascular-related emergency department visits occurred in 17 (4%) patients in the low sodium diet group and 15 (4%) patients in the usual care group (HR 1·21 [0·60-2·41]; p=0·60). No safety events related to the study treatment were reported in either group. In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events. Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Effect of sodium reduction based on the DASH diet on blood pressure in hypertensive patients with type 2 diabetes.

Objectives: to evaluate the effect of sodium reduction based on a modified DASH diet on blood pressure in hypertensive patients with type 2 diabetes. Material and methods: sixty-one hypertensive patients with type 2 diabetes were selected from the community and randomly allocated to a common salt group and low sodium salt group receiving the 8-week dietary intervention, in which weeks 1-2 was the dietary guidance phase, weeks 3-4 was the centralized feeding phase, and weeks 5-8 was the home medical care phase. Participants were followed up in the hospital once a week to collect information on outpatient blood pressure, salt, and drug use. Physical examinations were conducted at 4 weeks and the end of the intervention, as well as at baseline. Results: after the intervention, the blood pressure of both the low sodium group (SBP: -14.32 mmHg, p < 0.001; DBP: -6.32mmHg, p < 0.001) and the common salt group (SBP: -10.98 mmHg, p < 0.001; DBP: -5.24 mmHg, p = 0.001) decreased significantly with a more pronounced decrease in the low sodium group but no statistically significant differences between the two groups (SBP: -0.28 mmHg, p = 0.929; DBP: -3.32 mmHg, p = 0.093). At the end of the intervention, sodium intake was significantly decreased, but potassium intake was increased in the low sodium group (p < 0.05); however, the common salt group had no significant change. Conclusion: reducing sodium intake based on the modified DASH diet had a good effect on systolic and diastolic blood pressure in hypertensive patients with type 2 diabetes. Sodium reduction based on the modified DASH diet is safe and effective, and can be used as a guide for healthy living in hypertensive patients.

A randomized, double-blind clinical trial to evaluate the blood pressure lowing effect of low-sodium salt substitution on middle-aged and elderly hypertensive patients with different plasma renin concentrations.

This study aimed to evaluate the blood pressure (BP) lowing effect of low‐sodium (LS) salt substitution and how the effect influenced by plasma renin concentration (PRC) on middle‐aged and elderly hypertensive patients. Three hundred fifty‐two hypertensives were randomized at a 1:1 ratio into a LS group and a normal salt (NS) group. We compared intergroup changes observed in office blood pressure measurement (OBPM) and home blood pressure measurement (HBPM). Then, all patients in LS group were divided into tertiles according to baseline PRC, aldosterone concentration, and aldosterone/renin ratio (ARR), and changes in OBPM and HBPM were compared across the three tertile subgroups. Follow‐up surveys were completed by 322 patients. The intergroup net reduction in systolic OBPM, systolic HBPM, and diastolic HBPM was −6.6, −4.6, and −2.3 mmHg, respectively (all P < .05), and −1.8 mmHg in diastolic OBPM (P = .068). There was a more significant reduction in OBPM and HBPM among the low baseline PRC subgroup than among the high PRC subgroup. There were no significant differences in the changes in OBPM and HBPM between the three subgroups when grouped according to baseline aldosterone concentration. The reduction in OBPM and HBPM in the high tertile of ARR was larger than that in the low tertile subgroup. LS salt substitution is effective in reducing systolic OBPM, systolic HBPM, and diastolic HBPM in middle‐aged and elderly hypertensive patients. LS salt substitution may offer a non‐pharmaceutical therapy for hypertensive patients. Baseline PRC may be a marker to predict BP response after salt restriction.

The Feasibility of Using Computrition Software for Nutrition Research

Abstract Objectives Computrition is a food service software utilized by dieticians in clinical settings to create recipes, design menus, and scale the menus to larger quantities, yet it is underutilized in the research setting. The objective was to determine the practicality of administering two meal plans (low sodium vs typical sodium) designed with Computrition in a double-blind, randomized pilot study in older adult residents of a congregate housing facility. Methods This pilot study included 19 females and 1 male aged ≥65y residing at Jack Satter House, Revere, MA. Participants were randomized to low sodium or typical sodium meals (&amp;lt;0.95 or &amp;gt;2 mg/kcal), designed with Computrition. A base 7-day meal plan (with breakfast, lunch, dinner, and two snacks) was generated. Recipes entered in Computrition were modified to reach three calorie levels (1750, 2000, 2250 kcal/d) and two sodium densities, while keeping potassium levels constant at ∼3500 mg/d. Finally, Computrition labels were generated to execute meals while maintaining blinding. To determine efficacy of these meal plans, compliance was evaluated by comparing change in urinary sodium (mmol/L) over 2-weeks between low sodium vs. typical sodium groups. These comparisons were also assessed in sub-groups by calorie intake (≤1750 kcal/d, n = 12 and ≥2000 kcal/d, n = 8). Results Mean age was 77 ± 6y and calorie intake was 1849 kcal (low sodium group, n = 11) and 80 ± 9y and 1785 kcal (typical sodium group, n = 9). Over 2-weeks, urinary sodium decreased by −30.6 mmol/L in the low sodium diet, compared to 2.4 mmol/L in the typical sodium diet (P = 0.003). In those consuming ≤ 1750 kcal/d on the low sodium diet, urinary sodium decreased non-significantly by −18.3 mmol/L, compared to −2.3 mmol/L in the typical sodium diet (P = 0.16). In those consuming ≥2000 kcal/d on the low sodium diet, urinary sodium decreased non-significantly by −22.0 mmol/L, compared to no change in the typical sodium diet (P = 0.26). Conclusions In this study, two sodium meal plans designed using Computrition altered urinary sodium over 2 weeks. Similar trends in reduction were seen in the sub-groups by calorie intake, although results were not significant due to small sample sizes. Future work should evaluate testing and standardization of this software for a multi-site nutrition intervention study. Funding Sources ISAC, Marcus Institute, Hebrew SeniorLife.

LEFT VENTRICULAR DIASTOLIC FUNCTION IN RELATION TO SODIUM DIETARY INTAKE AND RENAL HANDLING

Objective: Sodium load has been associated with blood pressure (BP) and target organ damage. Sodium sensitivity of BP varies between individuals and may be determined by renal sodium handling. The present study aimed to investigate ambulatory blood pressure and left ventricular diastolic function in relation to interaction between sodium dietary intake and renal handling. Design and method: We recruited 303 (mean age, 46.9 years; 55% women) members from randomly selected families. The 24-hour blood pressure monitoring was assessed. Left ventricular mass index, left atrium (LA) diameter, and the ratio of early (E) and late (A) diastolic peak of transmitral flow velocities (E/A) as well as the ratio of E to tissue doppler early diastolic mitral annular velocity (Em) were assessed by echocardiography (VIVID 7). Serum and urinary sodium concentration was measured using an automatic analyzer while lithium concentration by automatic absorption spectrometry. The median value of urinary sodium excretion (uNa) and median value of fractional urinary lithium excretion (FELi) - marker of sodium reabsorption in proximal tubules and as a consequence sodium sensitivity - were calculated. Results: To evaluate the influence of high sodium diet on parameters of interest we divided participants on two groups: high sodium group (HNa) constituted 86 participants with uNa above the median value (156.6 mmol/day) and FELi below the median value (16.6%), while the low sodium group (LNa) combined 79 persons with uNa below and FELi above the respective median value. 24-hour systolic and diastolic BP, left atrium diameter and E/Em were higher in HNa group in comparison to LNa participants (p < 0.05). After adjusting for relatedness, age, gender, and antihypertensive treatment, significant differences between predefined groups in 24-hour systolic BP (120.2 vs 117.0 (mmHg), p = 0.03) and E/Em (7.3 vs 6.7(%), p = 0.016) ratio persisted. Conclusions: The study may be the basis for an assumption that in participants with a paradoxical high renal sodium retention in case of sodium overload an impairment of cardiac diastolic function develops sooner, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Hyponatremia Predicts Poor Outcomes in Patients With Chronic Kidney Disease Undergoing Heart Operation

Preoperative hyponatremia adversely affects outcomes of cardiothoracic operation. However, in patients with chronic kidney disease, the association of sodium levels on postoperative events has never been evaluated. We investigated the impact of preoperative hyponatremia on outcomes after cardiac operation in patients with non-dialysis-dependent chronic kidney disease. Primary end points were operative mortality and acute kidney injury that required dialysis. Secondary end points were major infection and long-term survival. The study is observational and includes all patients with stage III to IV chronic kidney disease (non-dialysis) undergoing cardiac operation between February 2000 and January 2016. Patients were stratified into two groups by preoperative sodium levels: sodium less than 135 mEq/L and sodium of 135 mEq/L or more. There were 1,008 patients (mean estimated glomerular filtration rate [GFR]: 43 ± 14 mL • min-1 • 1.73m-2) with 92 patients (9%) in the low-sodium group. Patients with low sodium had higher operative mortality (p= 0.0004), need for new dialysis (p= 0.0008), and infection (p= 0.002). Predictors of operative mortality were European System for Cardiac Operative Risk Evaluation(EuroSCORE) (hazard ratio [HR] 1.03. 95% confidence interval [CI]: 1.02 to 1.05, p < 0.0001), decreasing values of sodium (HR 1.14. 95% CI: 1.07 to 1.2, p= 0.0002), and decreasing values of GFR (HR 1.01, 95% CI: 1.003 to 1.03, p= 0.007). Sodium less than 135 mEq/L was independently associated with increased need for dialysis (HR 1.3, 95% CI: 1.1 to 1.7, p= 0.0008). By linear regression, decreasing values of preoperative sodium were proportionate to the incidence of operative mortality (p < 0.0001) and need for dialysis (p < 0.0001). Preoperative hyponatremia is a predictor of increased mortality and other adverse events in patients with non-dialysis-dependent chronic kidney disease undergoing cardiac operation. These findings are similar to those in hyponatremic patients without kidney disease.

Intrarenal Mas and AT1 receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats.

What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin-(1-7) [Ang-(1-7)]-induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT1 receptors. What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT1 receptor blockade also had an inhibitory effect on Ang-(1-7)-induced natriuresis and diuresis. Thus, Ang-(1-7)-induced increases in sodium and water excretion are dependent upon functional Mas and AT1 receptors. We investigated whether angiotensin-(1-7) [Ang-(1-7)]-induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensinII type 1 (AT1 ) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93±4mmHg, 46.1±15.7μlmin-1 kg-1 and 1.4±0.3%, respectively, in the normal-sodium group and 91±2mmHg, 19.1±3.3μlmin-1 kg-1 and 0.7±0.2%, respectively, in the low-sodium group. Angiotensin-(1-7) infusion had no effect on mean arterial pressure in rats receiving a normal-sodium diet but decreased it by 4±5% in rats receiving a low-sodium diet (P<0.05). Interstitial Ang-(1-7) infusion increased urine flow twofold and fractional sodium excretion threefold (P<0.05) in rats receiving a normal-sodium diet and to a greater extent, approximately three- and fourfold, respectively, in rats receiving the low-sodium diet (both P<0.05). Angiotensin-(1-7)-induced increases in urine flow and fractional sodium excretion were absent in both dietary groups during intrarenal AT1 or Mas receptor inhibition after either losartan or A-779, respectively. Thus, AT1 receptor activation, as well as Mas receptor activation, plays an essential role in mediating Ang-(1-7)-induced natriuresis and diuresis. Whether this is because Ang-(1-7) partly antagonizes AT1 receptors or whether Ang-(1-7)-induced natriuresis is mediated through AT1 -Mas receptor dimerization remains unclear.

Moderate salt restriction with or without paricalcitol in type 2 diabetes and losartan-resistant macroalbuminuria (PROCEED): a randomised, double-blind, placebo-controlled, crossover trial

Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. We aimed to assess the albuminuria-lowering effects of salt restriction, paricalcitol therapy, or both, in this population. In this randomised, double-blind, placebo-controlled, crossover trial, we recruited adult patients with type 2 diabetes from six diabetology outpatient clinics in northern Italy, with 24 h albuminuria of more than 300 mg despite 100 mg per day losartan therapy, blood pressure of less than 140/90 mm Hg, serum creatinine concentration of less than 2 mg/dL, stable renal function on stable renin-angiotensin system inhibitor therapy with a fixed dose of losartan, parathyroid hormone concentration of 20 pg/mL to <110 pg/mL, serum calcium concentration of less than 9·5 mg/dL, and serum phosphate concentration of less than 5 mg/dL, who had been more than 80% compliant with placebo treatment during a 1 month placebo run-in. We allocated patients 1:1 with computer-generated randomisation to an open-label 3 month high-sodium (>200 mEq [4·8 g] per day) or low-sodium (<100 mEq [2·4 g] per day) diet and, within each diet group, to a 1 month double-blind treatment period of oral paricalcitol (2 μg per day) or placebo, followed by 1 month of placebo washout and then a further 1 month double-blind treatment period of paricalcitol or placebo in which patients crossed over to the opposite treatment period. The primary outcome was 24 h albuminuria (median of three consecutive measurements). Analyses were modified intention-to-treat (including all randomly allocated patients who took at least one dose of study drug and had an efficacy measurement after the first treatment period). Patients and investigators were masked to paricalcitol and placebo assignment. Those assessing outcomes were masked to both study drug and diet assignment. This study is registered with ClinicalTrials.gov, number NCT01393808, and the European Union Clinical Trials Register, number 2011-001713-14. Between Dec 13, 2011, and Feb 17, 2015, we randomly allocated 57 (50%) patients to a low-sodium diet (28 [49%] to paricalcitol then placebo and 29 [51%] to placebo then paricalcitol) and 58 (50%) to a high-sodium diet (29 [50%] to paricalcitol then placebo and 29 [50%] to placebo then paricalcitol). In the low-sodium group (30 mEq of daily sodium intake reduction, equivalent to approximately 1·7-1·8 g per day), 24 h albuminuria was reduced by 36·6% (95% CI 28·5-44·9) from 724 mg (441-1233) at baseline to 481 mg (289-837) at month 3 (p<0·0001), but no significant change occurred in the high-sodium group (from 730 mg [416-1227] to 801 mg [441-1365]; 2·9% [-16·8 to 16·4] increase; p=0·50). Changes between diet groups differed by 32·4% (17·2-48·8; p<0·0001) and correlated with changes in natriuresis (r=0·43; p<0·0001). On the high-sodium diet, paricalcitol reduced the salt-induced albuminuria increase by 17·8% (3·9-32·3) over the month of treatment compared with placebo (p=0·02), whereas on the low-sodium diet, paricalcitol did not have a significant effect versus placebo (increase of 4·1% [-9·3 to 21·6]; p=0·59). During placebo treatment, albuminuria decreased with the low-sodium diet (p=0·0002) and did not significantly change with the high-sodium diet, but changes were significantly different between diet groups (p=0·0004). Treatment was well tolerated and no patients withdrew from the study because of treatment-related effects. 67 adverse events occurred in 52 (45%) patients during paricalcitol treatment and 44 events occurred in 36 (31%) patients during placebo treatment. During paricalcitol therapy, 14 cases of hypercalciuria, six cases of hypercalcaemia, and five cases of hyperphosphataemia were reported in one patient each, all of which were possibly treatment related. One case of hypercalciuria was reported in one patient during the placebo treatment period. One stroke and one coronary event occurred during paricalcitol therapy. No patients died during the study. In patients with macroalbuminuria and type 2 diabetes, moderate salt restriction enhances the antialbuminuric effect of losartan, an effect that could be nephroprotective and cardioprotective in the long term. The finding that paricalcitol prevents a sodium-induced increase in albuminuria provides support for trials to test the long-term risk-benefit profile of paricalcitol add-on therapy in patients with type 2 diabetes and macroalbuminuria refractory to dietary salt restriction, including patients refractory to even moderate salt restriction. AbbVie.

Ototoxicity associated with topical administration of diclofenac sodium as an otic drop: An experimental animal study

ObjectivesThe aim of the study is to evaluate the ototoxicity of topical diclofenac sodium in comparison to positive and negative controls prior to the investigation of analgesic and anti-inflammatory efficacy of the agent in otic administration. MethodsTwenty four ears of 12 guinea pigs were included in the study. Wide myringotomy was performed on all tympanic membranes under general anesthesia and auditory brainstem responses (ABR) were evaluated. The subjects were separated into four groups, two groups received diclofenac sodium at low and high doses, positive controls received gentamicin and negative controls received isotonic sodium chloride topically for 14 days and ABRs were reevaluated. ResultsNo significant difference were observed between the pre and post-treatment click response, 1 kHz and 8 kHz response threshold levels after isotonic sodium chloride administration. All threshold levels were elevated in the positive control group. In the low and high dose diclofenac sodium groups, click response, 1 kHz and 8 kHz response threshold levels were significantly higher compared to the baseline values. Pre and post-treatment mean threshold level changes were not significantly different between the low and high dose diclofenac sodium groups. Pre and post-treatment mean threshold level changes in the gentamicin group were not significantly different from low or high dose diclofenac sodium groups. ConclusionDiclofenac sodium, considered as an analgesic and anti-inflammatory otic preparation, is shown to be as ototoxic as gentamicin in chronic use which may lead to loss of hearing especially when used topically in chronic otitis cases with tympanic membrane damage.

Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial.

Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+ per day in the combined RS groups and 108±61 mmol Na+ per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.

Hyponatraemia In Cerebral Malaria And Association With Outcome

Cerebral malaria is a severe and potentially fatal neurological manifestation of malaria. Hyponatremia is observed in the majority of adult and pediatric patients with severe malaria. The importance of correcting the hyponatremia that complicates severe malaria is debated. A total of 60 cases of Cerebral Malaria studied in the Department of Paediatrics, Bal Chikitsalaya, MB Hospital, RNT Medical College, Udaipur, Rajasthan in between March 2015 to February 2016 for a period of one year. Total 40 (66.7%) was positive for P. falciparum, 11 (18.3%) for P. vivax and 9 (15%) for both P. falciparum and P. vivax. Total 44 (73.3%) patients were hyponatremic (<135 Meq/L), 28 (46.7%) had sodium level < 130 Meq/L and 2 (3.3%) patients had very low sodium (< 120 Meq/L). Total 30 patients of P.falciparum positive had low sodium (< 135 Meq/L). All patients had GCS < 11 and out of them maximum patients i.e. 42 (70%) belonged to low sodium group (121-134 Meq/L). 23 (38.3%) patients had deep coma (GCS ? 7) and out of them 13 (21.6%) were from low sodium group (121-134 Meq/L). Mortality was 7 (11.7%) and 6 were from low sodium group (< 135 Meq/L). In conclusion, this study showed that hyponatremia is a common feature in children presenting with Cerebral Malaria and it is associated with increased mortality. There is direct relationship between serum sodium and GCS. Thus, early detection, prompt management and adequate supportive therapy are key steps to reduce morbidity and mortality due to Cerebral Malaria.