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The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.
Raimann, JG, Chan, CT, Daugirdas, JT, Depner, T, Greene, T, Kaysen, GA, Kliger, AS, Kotanko, P, Larive, B, Beck, G, et al
Kidney & blood pressure research. 2021;(6):768-776
Abstract
INTRODUCTION The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. METHODS Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. RESULTS In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. DISCUSSION/CONCLUSION In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.
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Comparative analysis of visit and home blood pressure in a pilot trial on the effect of 18% sodium substitute salt on blood pressure.
Liu, T, Rao, H, Wang, M, Xu, H, Wang, W, Li, G, Wang, H, Mu, L
Scientific reports. 2021;(1):907
Abstract
Aim to compare the home blood pressure monitoring (HBPM) and visit blood pressure monitoring in a clinical phase I single-arm pilot trial. The 18% sodium substitute salt was used in 43 hypertensives for 8 weeks, and visited once a week, while weekly visit blood (VBP) pressure, daily home blood pressure (HBP) and urine test results before and after intervention were collected. 43 hypertensive patients were recruited, 4 were lost. And enrolled 39 patients for analysis. The VBP were lower than morning HBP and night HBP (P < 0.05). And VBP was good correlated with morning BP (SBP: r = 0.692, P < 0.001, DBP: r = 0.789, P < 0.001) and night BP (SBP: r = 0.571, P < 0.001, DBP: r = 0.738, P < 0.001). The results of mixed linear model analysis showed that patients' visit SBP (- 11.4 mmHg, 95% CI: - 17.0 to - 5.7, P < 0.001), morning home SBP (- 10.0 mmHg, 95% CI: - 16.4 to - 3.6, P = 0.003) and night home SBP (- 10.2 mmHg, 95% CI: - 15.8 to - 4.6, P = 0.001) decreased significantly, after intervention. Both HBP and VBP showed that 18% substitute salt intervention could decrease the blood pressure of hypertensives. Medication led to VBP lower than HBP, but the two still had a good correlation.Trial registration: NCT03226327. Registered 21 July 2017-Retrospectively registered, http://www.clinicaltrials.gov .
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Low Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children: A Prospective Diagnostic Accuracy Study.
Lindestam, U, Almström, M, Jacks, J, Malmquist, P, Lönnqvist, PA, Jensen, BL, Carlström, M, Krmar, RT, Svensson, JF, Norberg, Å, et al
European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. 2020;(4):350-356
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INTRODUCTION Early differentiation between perforated and nonperforated acute appendicitis (AA) in children is of major benefit for the selection of proper treatment. Based on pilot study data, we hypothesized that plasma sodium concentration at hospital admission is a diagnostic marker for perforation in children with AA. MATERIALS AND METHODS This was a prospective diagnostic accuracy study, including previously healthy children, 1 to 14 years of age, with AA. Blood sampling included plasma sodium concentration, plasma glucose, base excess, white blood cell count, plasma arginine vasopressin (AVP), and C-reactive protein. RESULTS Eighty children with histopathologically confirmed AA were included in the study. Median plasma sodium concentration on admission in patients with perforated AA (134 mmol/L, [interquartile range 132-136]) was significantly lower than in children with nonperforated AA (139 mmol/L, [137-140]). The receiver operating characteristic curve of plasma sodium concentration identifying patients with perforated AA showed an area under the curve of 0.93 (95% confidence interval, 0.87-0.99), with a sensitivity and specificity of 0.82 (0.70-0.90) and 0.87 (0.60-0.98), respectively. Plasma sodium concentrations ≤136 mmol/L resulted in an odds ratio of 31.9 (6.3-161.9) for perforation. The association between low plasma sodium concentration and perforated AA was confirmed in a multivariate logistic regression analysis. Median plasma AVP on admission was higher in patients with perforated (8.6 pg/mL [5.0-14.6]) as compared with nonperforated AA (3.4 pg/mL [2.5-6.6]). CONCLUSION In children with AA, there is a strong association between low plasma sodium concentration and perforation, a novel and not previously described finding.
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Dynamic Adjustments of Parenteral Support in Early Adult Intestinal Failure-Essential Role of Sodium.
Jacob, T, Glass, A, Witte, M, Reiner, J, Lamprecht, G
Nutrients. 2020;(11)
Abstract
Intestinal failure (IF) requires parenteral support (PS) substituting energy, water, and electrolytes to compensate intestinal losses and replenish deficits. Convalescence, adaptation, and reconstructive surgery facilitate PS reduction. We analyzed the effect of changes of PS on body mass index (BMI) in early adult IF. Energy, volume, and sodium content of PS and BMI were collected at the initial contact (FIRST), the time of maximal PS and BMI (MAX) and the last contact (LAST). Patients were categorized based on functional anatomy: small bowel enterostomy-group 1, jejuno-colic anastomosis-group 2. Analysis of variance was used to test the relative impact of changes in energy, volume, or sodium. Total of 50 patients were followed for 596 days. Although energy, volume, and sodium support were already high at FIRST, we increased PS to MAX, which was accompanied by a significant BMI increase. Thereafter PS could be reduced significantly, leading to a small BMI decrease in group 1, but not in group 2. Increased sodium support had a stronger impact on BMI than energy or volume. Total of 13 patients were weaned. Dynamic PS adjustments are required in the early phase of adult IF. Vigorous sodium support acts as an independent factor.
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Serum sodium levels and related treatment-emergent adverse events during eslicarbazepine acetate use in adults with epilepsy.
Wechsler, RT, Radtke, RA, Smith, M, Vossler, DG, Strom, L, Trinka, E, Cheng, H, Grinnell, T, Blum, D, Vieira, M, et al
Epilepsia. 2019;(7):1341-1352
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OBJECTIVE To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal- (partial-) onset seizures. METHODS This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400-1200 mg once daily), two phase 3 trials of ESL monotherapy (1200-1600 mg once daily), and their open-label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+ ]), incidences of hyponatremia-related treatment-emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. RESULTS The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open-label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+ ] measurement ≤125 mEq/L, <9% had a >10 mEq/L decrease in [Na+ ] from baseline, <6% had a hyponatremia-related TEAE, and <2% discontinued the controlled trials due to a hyponatremia-related TEAE. Hyponatremia appeared to be more frequent in the monotherapy (vs adjunctive therapy) trials; in the controlled trials of adjunctive ESL and ESL monotherapy, incidence generally increased with increasing ESL dose. The majority of patients with an investigator-reported TEAE of "hyponatremia" or "blood sodium decreased" did not have a corresponding laboratory [Na+ ] measurement ≤125 mEq/L. Some symptoms potentially related to hyponatremia (including nausea and vomiting) were more frequent in patients with a minimum postdose [Na+ ] measurement ≤125 mEq/L. SIGNIFICANCE Reductions in serum sodium concentrations and hyponatremia-related TEAEs occurred in a small number of patients taking ESL. Suspected hyponatremia should be confirmed and monitored via [Na+ ] measurements.
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SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial.
Karg, MV, Bosch, A, Kannenkeril, D, Striepe, K, Ott, C, Schneider, MP, Boemke-Zelch, F, Linz, P, Nagel, AM, Titze, J, et al
Cardiovascular diabetology. 2018;(1):5
Abstract
BACKGROUND AND AIMS Sodium tissue content by 23Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action. MATERIALS AND METHODS In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7.6 years) with type 2 diabetes were randomized to either dapagliflozin 10 mg or placebo once daily for 6 weeks each. In addition to metabolic parameters and ambulatory blood pressure (BP) we analysed the sodium content in the skin and muscles of the lower leg by Na-MRI. RESULTS Compared to baseline 6 weeks treatment with the SGLT-2 inhibitor dapagliflozin decreased fasting (132 ± 28 vs. 114 ± 19 mg/dl, p < 0.001), postprandial blood glucose (178 ± 66 mg/dl vs. 153 ± 46 mg/dl, p < 0.001), body weight (87.6 vs. 86.6 kg, p < 0.001) and systolic (129 ± 12 vs. 126 ± 11 mmHg, p = 0.010), and diastolic (77.4 ± 9 vs. 75.6 ± 8 mmHg, p = 0.024), 24-h ambulatory BP. Tissue sodium content in the skin was reduced after 6 weeks treatment with dapagliflozin compared to baseline [24.1 ± 6.6 vs. 22.7 ± 6.4 A.U.(arbitrary unit) p = 0.013]. No significant reduction of tissue sodium content was observed in the muscle (M. triceps surae: 20.5 ± 3.5 vs. 20.4 ± 3.7 A.U. p = 0.801). No clear significant difference in tissue water content of muscle and skin was observed after 6 weeks of treatment with dapagliflozin, compared to baseline. CONCLUSION SGLT-2 inhibition with dapagliflozin resulted in a significant decrease in tissue sodium content of the skin after 6 weeks. This observation point to a decrease of total sodium content in patients with type 2 diabetes prone to cardiovascular complications, that might be mitigated by SGLT-2 inhibition. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT02383238) retrospectively registered.
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Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study.
Kuwabara, M, Hisatome, I, Roncal-Jimenez, CA, Niwa, K, Andres-Hernando, A, Jensen, T, Bjornstad, P, Milagres, T, Cicerchi, C, Song, Z, et al
PloS one. 2017;(1):e0169137
Abstract
BACKGROUND Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD. METHODS This study was a large-scale, single-center, retrospective 5-year cohort study at Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects (age 35 to 85) without DM and/or CKD were enrolled. This analysis evaluated age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, hyperuricemia, fasting glucose, BUN, serum sodium, potassium, chloride and calculated serum osmolarity. RESULTS Elevated serum sodium was an independent risk factor for development of CKD (OR: 1.03, 95% CI, 1.00-1.07) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium. Calculated serum osmolarity was also an independent risk factor for CKD (OR: 1.04; 95% CI, 1.03-1.05) as was BUN (OR: 1.08; 95% CI, 1.06-1.10) (independent of serum creatinine). CONCLUSIONS Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD. This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD.
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Sodium balance, circadian BP rhythm, heart rate variability, and intrarenal renin-angiotensin-aldosterone and dopaminergic systems in acute phase of ARB therapy.
Isobe-Sasaki, Y, Fukuda, M, Ogiyama, Y, Sato, R, Miura, T, Fuwa, D, Mizuno, M, Matsuoka, T, Shibata, H, Ito, H, et al
Physiological reports. 2017;(11)
Abstract
We have revealed that even in humans, activated intrarenal renin-angiotensin-aldosterone system (RAAS) enhances tubular sodium reabsorption to facilitate salt sensitivity and nondipper rhythm of blood pressure (BP), and that angiotensin receptor blocker (ARB) could increase daytime urinary sodium excretion rate (UNaV) to produce lower sodium balance and restore nondipper rhythm. However, the sympathetic nervous system and intrarenal dopaminergic system can also contribute to renal sodium handling. A total of 20 patients with chronic kidney disease (61 ± 15 years) underwent 24-h ambulatory BP monitoring before and during two-day treatment with ARB, azilsartan. Urinary angiotensinogen excretion rate (UAGTV, μg/gCre) was measured as intrarenal RAAS; urinary dopamine excretion rate (UDAV, pg/gCre) as intrarenal dopaminergic system; heart rate variabilities (HRV, calculated from 24-h Holter-ECG) of non-Gaussianity index λ25s as sympathetic nerve activity; and power of high-frequency (HF) component or deceleration capacity (DC) as parasympathetic nerve activity. At baseline, glomerular filtration rate correlated inversely with UAGTV (r = -0.47, P = 0.04) and positively with UDAV (r = 0.58, P = 0.009). HF was a determinant of night/day BP ratio (β = -0.50, F = 5.8), rather than DC or λ25s During the acute phase of ARB treatment, a lower steady sodium balance was not achieved. Increase in daytime UNaV preceded restoration of BP rhythm, accompanied by decreased UAGTV (r = -0.88, P = 0.05) and increased UDAV (r = 0.87, P = 0.05), but with no changes in HRVs. Diminished sodium excretion can cause nondipper BP rhythm. This was attributable to intrarenal RAAS and dopaminergic system and impaired parasympathetic nerve activity. During the acute phase of ARB treatment, cooperative effects of ARB and intrarenal dopaminergic system exert natriuresis to restore circadian BP rhythm.
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The prognostic significance of serum sodium in a population undergoing cardiac resynchronisation therapy.
Guha, K, Spießhöfer, J, Hartley, A, Pearse, S, Xiu, PY, Sharma, R
Indian heart journal. 2017;(5):613-618
Abstract
PURPOSE To determine the prognostic implications of changes towards hyponatremia at varying time-points in the treatment of patients undergoing cardiac resynchronisation therapy (CRT). METHODS A retrospective series of 249 patients was studied from 2002 to 2013. The population was categorized on the basis of serum sodium profile at baseline, at 1 month and at 6 month follow up visits following successful CRT implantation. The composite endpoint was all-cause mortality and heart failure hospitalisation (defined by the need for intravenous diuretic therapy) following CRT implantation. RESULTS A total of 249 patients (67.8±12.5 years; NYHA class III/IV 75; LVEF 27.2±8.8%) were followed up for a median of 5.5 years. Hyponatremia at baseline, 1 month or 6 months follow up did not predict the composite endpoint. 26% of patients showed hyponatremia at baseline prior to CRT implantation, while it was present in 19.9% of patients 1 month (p=0.003) and in 16% (p<0.001) 6 months after CRT implantation. There was a significantly worse outcome for those patients who developed hyponatremia 6 months after CRT implantation. In multivariate analysis, the intake of loop diuretics (HR 1.76 [1.04-2.95], p=0.03) and renal impairment (urea>7.0mmol/l) (HR 1.61 [1.05-2.46], p=0.03) at baseline were associated with an increased risk of unplanned heart failure hospitalisation and all-cause mortality after CRT implantation. CONCLUSIONS A change towards hyponatremia when observed 6 months after CRT implantation may predict a worse clinical outcome. Additionally, renal impairment and higher diuretic doses are associated with an increased risk of mortality in the population analysed.
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Urinary Sodium-to-Potassium Ratio Tracks the Changes in Salt Intake during an Experimental Feeding Study Using Standardized Low-Salt and High-Salt Meals among Healthy Japanese Volunteers.
Yatabe, MS, Iwahori, T, Watanabe, A, Takano, K, Sanada, H, Watanabe, T, Ichihara, A, Felder, RA, Miura, K, Ueshima, H, et al
Nutrients. 2017;(9)
Abstract
The Na/K ratio is considered to be a useful index, the monitoring of which allows an effective Na reduction and K increase, because practical methods (self-monitoring devices and reliable individual estimates from spot urine) are available for assessing these levels in individuals. An intervention trial for lowering the Na/K ratio has demonstrated that a reduction of the Na/K ratio mainly involved Na reduction, with only a small change in K. The present study aimed to clarify the relationship between dietary Na intake and the urinary Na/K molar ratio, using standardized low- and high-salt diets, with an equal dietary K intake, to determine the corresponding Na/K ratio. Fourteen healthy young adult volunteers ingested low-salt (3 g salt per day) and high-salt (20 g salt per day) meals for seven days each. Using a portable urinary Na/K meter, participants measured their spot urine at each voiding, and 24-h urine was collected on the last day of each diet period. On the last day of the unrestricted, low-salt, and high-salt diet periods, the group averages of the 24-h urine Na/K ratio were 4.2, 1.0, and 6.9, while the group averages of the daily mean spot urine Na/K ratio were 4.2, 1.1, and 6.6, respectively. The urinary Na/K ratio tracked changes in dietary salt intake, and reached a plateau approximately three days after each change in diet. Frequent monitoring of the spot urine Na/K ratio may help individuals adhere to an appropriate dietary Na intake.