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[Sodium metabolism: An update in 2019].
Robert, A, Cheddani, L, Ebel, A, Vilaine, E, Seidowsky, A, Massy, Z, Essig, M
Nephrologie & therapeutique. 2020;(2):77-82
Abstract
The classical theory of sodium metabolism considers mostly its role on the extracellular volume according to a daily response to the variations of salt intake, correlated to the variations of water volume. Recent works consider sodium tissular storage. This non-osmotic pool could play a role in blood pressure regulation and in immunity mechanisms. The regulation modalities could be more complex, organised over the long term, with a modification of the sodium-water relationship. The aim of this article is to give a new insight on sodium metabolism, based on recent works, especially on the role and regulation of non osmotic tissular sodium.
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
Huang, L, Tian, M, Yu, J, Li, Q, Liu, Y, Yin, X, Wu, JH, Marklund, M, Wu, Y, Li, N, et al
American heart journal. 2020;:136-145
Abstract
The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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The efficacy and safety of low dialysate sodium levels for patients with maintenance haemodialysis: A systematic review and meta-analysis.
Geng, X, Song, Y, Hou, B, Ma, Y, Wang, Y
International journal of surgery (London, England). 2020;:332-339
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Abstract
BACKGROUND & AIM: Fluid overload and hypertension frequently results in cardiovascular disease, which is one of the leading causes of death in dialysis patients. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing cardiovascular disease morbidity and mortality. This meta-analysis was designed to evaluate the efficacy and safety of using a low (<138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. METHODS We searched the Cochrane Library, PubMed, EMBASE, Web of Science up to August 22, 2019. Randomised controlled trials (RCTs), both parallel and cross-over, of low (<138 mM) versus neutral (138-140 mM) or high (>140 mM) dialysate [Na+] for maintenance HD patients were included. Mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2. RESULTS 12 Randomised controlled trials with 390 patients were included in this meta-analysis. Of these studies, three studies were parallel group, and the remaining nine were crossover. Compared to neutral or high dialysate [Na+], low dialysate [Na+] reduced dialysis mean arterial pressure (MAP) with a pooled MD of -3.38 mmHg (95% CI -4.57 to -2.19; P < 0.00001), reduced interdialytic weight gain with a pooled MD of -0.35 kg (95% CI -0.51 to -0.18; P < 0.0001), reduced predialysis serum [Na+] with a pooled MD of -2.62 mM (95% CI -3.59 to -1.66; P < 0.00001). In contrast, low dialysate [Na+] increased intradialytic hypotension events with a pooled RR of 1.54 (95% CI 1.16 to 2.05; P = 0.003), increased the incidence of intradialytic cramps with a pooled RR of 1.77 (95% CI 1.15 to 2.73; P = 0.01). However, no difference was found between lower and higher dialysate [Na+] in systolic blood pressure and diastolic blood pressure. CONCLUSIONS Though our pooled result indicated that low dialysate [Na+] reduced MAP, interdialytic weight gain and predialysis serum [Na+] significantly, it also indicated that low dialysate [Na+] could increase the incidence of intradialytic hypotension and intradialytic cramps events. Considering the contradiction in efficacy and safety of low dialysate [Na+] in our analysis, future larger and up-to-date definitive studies are needed to evaluate the medium to long-term effects of low sodium levels in dialysis fluid, and better inform clinical practice.
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Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study.
Martens, RJH, Henry, RMA, Bekers, O, Dagnelie, PC, van Dongen, MCJM, Eussen, SJPM, van Greevenbroek, M, Kroon, AA, Stehouwer, CDA, Wesselius, A, et al
The Journal of nutrition. 2020;(6):1413-1424
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BACKGROUND It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood. OBJECTIVES We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction. METHODS We included 2961 participants from the population-based Maastricht Study (mean ± SD age 59.8 ± 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors. RESULTS Median [IQR] 24-h UNaE and UKE were 3.7 [2.8-4.7] g/24 h and 3.0 [2.4-3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium. CONCLUSIONS Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.
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Preeclampsia and low sodium (PALS): A case and systematic review.
Powel, JE, Rosenthal, E, Roman, A, Chasen, ST, Berghella, V
European journal of obstetrics, gynecology, and reproductive biology. 2020;:14-20
Abstract
Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures.
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Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses.
Zanetti, D, Bergman, H, Burgess, S, Assimes, TL, Bhalla, V, Ingelsson, E
Hypertension (Dallas, Tex. : 1979). 2020;(3):714-722
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Urinary biomarkers are associated with cardiovascular disease, but the nature of these associations is not well understood. We performed multivariable-adjusted regression models to assess associations of random spot measurements of the urine sodium-potassium ratio (UNa/UK) and urine albumin adjusted for creatinine with cardiovascular risk factors, cardiovascular disease, and type 2 diabetes mellitus (T2D) in 478 311 participants of the UK Biobank. Further, we assessed the causal relationships of these kidney biomarkers, used as proxies for kidney function, with cardiovascular outcomes using the 2-sample Mendelian randomization approach. In observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation, coronary artery disease, ischemic stroke, lipid-lowering medication, and T2D. In contrast, urine albumin adjusted for creatinine showed significant positive associations with atrial fibrillation, coronary artery disease, heart failure, hemorrhagic stroke, lipid-lowering medication, and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with BP (β systolic BP ≥2.63; β diastolic BP ≥0.85 SD increase in BP per SD change in UNa/UK and urine albumin adjusted for creatinine; P≤0.04), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.
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Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia.
Omar, HR, Guglin, M
Heart, lung & circulation. 2020;(2):233-241
Abstract
BACKGROUND Diuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. METHODS The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. RESULTS Patients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation-all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. CONCLUSION Patients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.
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Effect of Steamed Potato Bread Intake on Glucose, Lipids, and Urinary Na+ and K+: A Randomized Controlled Trial with Adolescents.
Xu, H, Guo, Y, Lu, S, Ma, Y, Wang, X, Zhao, L, Sun, J
International journal of environmental research and public health. 2020;(6)
Abstract
Although potatoes are highly nutritious, many epidemiological studies have connected their consumption with abnormal lipids, diabetes, and hypertension. Steamed potato bread has recently become one of China's staple foods. A randomized controlled trial was designed to evaluate the effect of steamed potato bread consumption on Chinese adolescents. Four classes from a high school were randomly selected and assigned to the intervention group (two classes) or control group (two classes). The steamed wheat bread (100% raw wheat flour) and potato bread (raw wheat flour to cooked potato flour ratio of 3:7) were provided to the control group and intervention group as staple food once a school day for 8 weeks, respectively. Compared with the control group, the intervention group had significant net changes in systolic blood pressure (4.6 mmHg, p = 0.010), insulin (-4.35 mIU/L, p < 0.001), total cholesterol (-0.13 mmol/L, p = 0.032), and high-density lipoproteins cholesterol (-0.07 mmol/L, p = 0.010). The urinary level of Na+/K+ did not differ between the groups. In conclusion, the intake of steamed potato bread for 8 weeks resulted in positive effects on the total cholesterol and insulin profiles but a negative effect on the systolic blood pressure and high-density lipoproteins cholesterol of adolescents.
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Dietary potassium restriction attenuates urinary sodium wasting in the generalized form of pseudohypoaldosteronism type 1.
Adachi, M, Tajima, T, Muroya, K
CEN case reports. 2020;(2):133-137
Abstract
Owing to its rarity and severe nature, the treatment for generalized pseudohypoaldosteronism type 1 (PHA1), a genetic disorder in the epithelial sodium channel (ENaC), is exclusively experience-based. In particular, the usefulness of dietary potassium restriction in PHA1 remains unclear with the absence of theoretical background to elucidate its utility. First, we demonstrated the effect of potassium restriction in a 13-month-old patient with ENaC γ-subunit gene mutations via a retrospective chart review; reduction of daily dietary potassium intake from 40 to 20 mEq induced rapid restoration of volume depletion, as evidenced by weight gain, elevation of the serum sodium level from 133 to 141 mEq/L, decreased urinary sodium excretion, and normalized renin activity. The serum potassium level decreased from 5.6 to 4.5 mEq/L. Next, we attempted to elucidate the pathophysiological basis of the usefulness of potassium restriction, leveraged by the increased knowledge regarding the roles of with-no-lysine kinases (WNKs) in the distal nephron. When potassium is restricted, the WNK signal will turn "on" in the distal nephron via reduction in the intracellular chloride level. Consequently, the sodium reabsorption from the Na+Cl- cotransporter (NCC) in the distal convoluted tubule and possibly from pendrin in the β-intercalated cell will increase. Thus, potassium restriction causes NCC and pendrin to compensate for the non-functional ENaC in the collecting duct. In conclusion, dietary potassium restriction is one of the indispensable treatments for generalized PHA1.
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Application of a quantum genetic algorithm and QTAIM analysis in the study of structural and electronic properties of neutral bimetallic clusters NaxLiy (4 ≤ x + y ≤ 10).
Silva, FT, Rocha-Santos, A, Firme, CL, De Souza, LA, Anjos, IC, Belchior, JC
Journal of molecular modeling. 2020;(11):317
Abstract
Alloy clusters of NaxLiy (4 ≤ x + y ≤ 10) are studied by exploring the potential energy surface in the ab initio MP2 level with the support of a quantum genetic algorithm (QGA). In some cases, the structures have been also refined with DFT and coupled-cluster methods. The general trends of sodium-lithium structures are in line with previous studies. The ionization potentials and polarizabilities to all structures were calculated with MP2 method and the average error between these two properties compared with experimental data was 6% and 13%, respectively. The topological analysis based on quantum theory of atoms in molecules (QTAIM) showed that by increasing the cluster size of the diatomic system there was a decrease of atomic interaction energies. The degree of degeneracy from D3BIA aromaticity index and the analysis of the atomic charges showed the influence (by charge transfer) of the chemical element in lower quantity in the cluster with respect to the other atoms. Our achievements of comparing our theoretical results with available experimental data have demonstrated that our approach can also predict satisfactorily quantum atomic and alloy clusters properties, at least, for low nuclearities.