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New advances in renal mechanisms of high fructose-induced salt-sensitive hypertension.
Xu, CM, Yang, TX
Sheng li xue bao : [Acta physiologica Sinica]. 2018;(6):581-590
Abstract
Fructose intake has increased dramatically over the past century and the upward trend has continued until recently. Increasing evidence suggests that the excessive intake of fructose induces salt-sensitive hypertension. While the underlying mechanism is complex, the kidney likely plays a major role. This review will highlight recent advances in the renal mechanisms of fructose-induced salt-sensitive hypertension, including (pro)renin receptor-dependent activation of intrarenal renin-angiotensin system, increased nephron Na+ transport activity via sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, increased renal uric acid production, decreased renal nitric oxide production, and increased renal reactive oxygen species production, and suggest actions based on these mechanisms that have therapeutic implications.
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2.
Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials.
Garofalo, C, Borrelli, S, Provenzano, M, De Stefano, T, Vita, C, Chiodini, P, Minutolo, R, De Nicola, L, Conte, G
Nutrients. 2018;(6)
Abstract
BACKGROUND A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. METHODS We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. RESULTS Eleven RCTs were selected and included information about 738 CKD patients (Stage 1⁻4); urinary sodium excretion was 104 mEq/day (95%CI, 76⁻131) and 179 mEq/day (95%CI, 165⁻193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p <0.001). Overall, mean differences in clinic and ambulatory systolic BP were −4.9 mmHg (95%CI from −6.8 to −3.1, p <0.001) and −5.9 mmHg (95%CI from −9.5 to −2.3, p <0.001), respectively, while clinic and ambulatory diastolic BP were −2.3 mmHg (95%CI from −3.5 to −1.2, p <0.001) and −3.0 mmHg (95%CI from −4.3 to −1.7; p <0.001), respectively. Mean differences in proteinuria and albuminuria were −0.39 g/day (95%CI from −0.55 to −0.22, p <0.001) and −0.05 g/day (95%CI from −0.09 to −0.01, p = 0.013). CONCLUSION Moderate salt restriction significantly reduces BP and proteinuria/albuminuria in patients with CKD (Stage 1⁻4).
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Prevalence of masked hypertension among children with risk factors for arterial hypertension.
Iturzaeta, A, Pompozzi, L, Casas Rey, C, Passarelli, I, Torres, F
Archivos argentinos de pediatria. 2018;(5):328-332
Abstract
INTRODUCTION Masked hypertension (MH) in children is defined as normal office blood pressure values and high values outside the clinical setting. The 24-hour ambulatory blood pressure monitoring (ABPM) is helpful for diagnosis. There is little information on MH prevalence in our population. OBJECTIVE To estimate the prevalence of MH in children with risk factors for arterial hypertension. MATERIAL AND METHOD Prospective, observational, cross-sectional study. Patients seen at Hospital General de Niños "P. de Elizalde" between July 1st, 2015 and December 1st, 2016, aged 5-11 years, with normal blood pressure and at least one risk factor for arterial hypertension were included in consecutive order. A 24-hour ABPM was done (SpaceLabs 90207/90217). Estimated sample: 110 patients. All relevant authorizations were obtained. RESULTS One hundred and ten patients aged 8.7 ± 1.8 years were included; 60 were girls. ABPM duration: 23.18 ± 1.8 hours. Twenty-three patients had neonatal history; all had at least one factor corresponding to personal history (the most common ones were increased salt intake and obesity); 101 had at least one factor corresponding to family history. ABPM helped to identify 10 patients with MH (9.1%; 95% confidence interval |-1;CI|-3;: 5.1-15.9); 7 had isolated nocturnal hypertension (6.4%; 95% CI: 3.1-23.5) and 28 had prehypertension (25.4%; 95% CI: 18.234.3). Among the 10 patients with MH, 7 were boys, 9 were obese and had at least one factor corresponding to family history. CONCLUSION The prevalence of MH in children with risk factors for arterial hypertension was close to 10%.
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[Sodium, hypertension, chronic kidney diseases, and public health].
Keller, N, Krummel, T, Hannedouche, T
Nephrologie & therapeutique. 2018;:S93-S98
Abstract
Salt consumption has substantially increased these last years in our modern societies and far exceeds our needs. It has a great impact on cardiovascular and renal disease and represents a major issue in public health. The present work is a review of observational and interventional studies exploring the relationship between salt consumption, high-blood pressure and cardiovascular morbimortality in the general population but also in chronic kidney diseases.
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Population dietary salt reduction and the risk of cardiovascular disease. A scientific statement from the European Salt Action Network.
Cappuccio, FP, Beer, M, Strazzullo, P, ,
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2018;(2):107-114
Abstract
The publication in the last few years of a number of prospective observational studies suggesting a J-shaped association between levels of salt (sodium) consumption and cardiovascular outcomes has opened a debate on the pertinence of population-wide salt reduction policies to reduce cardiovascular disease burden, and some have even questioned the global World Health Organization guidelines, that recommend a 30% reduction in salt consumption by 2025, aiming at an ideal target of no more than 5 g of salt consumption per day. In September 2018 the European Salt Action Network (E.S.A.N.), after appraising the quality of publications questioning the appropriateness of population salt reduction, discussed the scientific evidence and identified the pitfalls of recent data. The new evidence was deemed inadequate and, in places, biased by flawed methodology. These were identified in the biased assessment of sodium intake from spot urine and the use of the Kawasaki formula, the biased assessment of the sodium-outcome relationships in prospective observational studies using spot urine samples, the impact of reverse causality in such studies, the inadequate analytical approaches to data analysis, the lack of biological plausibility and the lack of precision in assessing long-term salt consumption, as recently demonstrated in studies using more stringent quality features in their study designs. On the basis of such appraisal, the E.S.A.N. agreed a statement confirming the support to the implementation of national and regional programmes of moderate reduction in salt intake, as recommended by the World Health Organization.
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Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study.
Gu, X, Gu, D, He, J, Rao, DC, Hixson, JE, Chen, J, Li, J, Huang, J, Wu, X, Rice, TK, et al
American journal of hypertension. 2018;(2):205-211
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Abstract
BACKGROUND A resequencing study of renal epithelial sodium channel (ENaC) genes was conducted to identify rare variants associated with blood pressure (BP) salt-sensitivity. METHODS The Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low-sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive and 300 most salt-resistant GenSalt participants were selected for the resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were resequenced using capillary-based sequencing methods. Traditional burden tests were utilized to examine association between rare variants and BP salt-sensitivity. Associations of low-frequency and common variants were tested using single-marker analyses. RESULTS Carriers of SCNN1A rare variants had a 0.52 [95% confidence interval (CI): 0.32-0.85] decreased odds of BP salt-sensitivity compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt-sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In single-marker analyses, 3 independent common variants in SCNN1A, rs11614164, rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni correction (P = 4.4 × 10-4, 1.1 × 10-8, and 1.3 × 10-3). Each copy of the minor allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23-1.52) increased odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and rs3741914 was associated with 0.68-fold (95% CI: 0.55-0.84) and 0.69-fold (95% CI: 0.54-0.86) decreased odds of salt-sensitivity, respectively. CONCLUSIONS This study demonstrated for the first time a relationship between rare variants in the ENaC pathway and BP salt-sensitivity. Future replication and functional studies are needed to confirm the findings in this study. CLINICAL TRIAL REGISTRY Trial Number NCT00721721.
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Comparative Efficacy of Antihypertensive Agents in Salt-Sensitive Hypertensive Patients: A Network Meta-Analysis.
Qi, H, Liu, Z, Cao, H, Sun, WP, Peng, WJ, Liu, B, Dong, SJ, Xiang, YT, Zhang, L
American journal of hypertension. 2018;(7):835-846
Abstract
BACKGROUND Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure (BP) in patients with SSH. METHODS We used sources as PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), CNKI, and WANFANG database from inception to November 2016. Studies that compared the efficacy of 2 or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure. RESULTS Twenty-five studies were involved in this meta-analysis. A calcium channel blocker (CCB) with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo (standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60 to 40.16), angiotensin receptor blockers (ARBs) (SMD, 95% CI: 22.94, 5.26 to 40.51), and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, CCB with metformin and moderate salt intake would decrease blood pressure with 17.90 mm Hg. CONCLUSIONS For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake was optimal in reducing BP, while CCB combined with metformin and moderate salt intake was the most efficacious at reducing BP in SSH patients with coexisting obesity.
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Self-monitoring of urinary salt excretion as a method of salt-reduction education: a parallel, randomized trial involving two groups.
Yasutake, K, Miyoshi, E, Misumi, Y, Kajiyama, T, Fukuda, T, Ishii, T, Moriguchi, R, Murata, Y, Ohe, K, Enjoji, M, et al
Public health nutrition. 2018;(12):2164-2173
Abstract
OBJECTIVE The present study aimed to evaluate salt-reduction education using a self-monitoring urinary salt-excretion device. DESIGN Parallel, randomized trial involving two groups. The following parameters were checked at baseline and endline of the intervention: salt check sheet, eating behaviour questionnaire, 24 h home urine collection, blood pressure before and after urine collection. SETTING The intervention group self-monitored urine salt excretion using a self-measuring device for 4 weeks. In the control group, urine salt excretion was measured, but the individuals were not informed of the result. SUBJECTS Seventy-eight individuals (control group, n 36; intervention group, n 42) collected two 24 h urine samples from a target population of 123 local resident volunteers. The samples were then analysed. RESULTS There were no differences in clinical background or related parameters between the two groups. The 24 h urinary Na:K ratio showed a significant decrease in the intervention group (-1·1) compared with the control group (-0·0; P=0·033). Blood pressure did not change in either group. The results of the salt check sheet did not change in the control group but were significantly lower in the intervention group. The score of the eating behaviour questionnaire did not change in the control group, but the intervention group showed a significant increase in eating behaviour stage. CONCLUSIONS Self-monitoring of urinary salt excretion helps to improve 24 h urinary Na:K, salt check sheet scores and stage of eating behaviour. Thus, usage of self-monitoring tools has an educational potential in salt intake reduction.
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Analysis of Sodium Chloride Intake and Treg/Th17 Lymphocytes in Healthy Individuals and Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus.
Vitales-Noyola, M, Layseca-Espinosa, E, Baranda, L, Abud-Mendoza, C, Niño-Moreno, P, Monsiváis-Urenda, A, Rosenstein, Y, González-Amaro, R
Journal of immunology research. 2018;:9627806
Abstract
We assessed different immune parameters in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with low (LSI) and high (HSI) sodium intake. Thirty-eight patients with RA, thirty-seven with SLE, and twenty-eight healthy subjects were studied and classified as LSI or HSI. Levels and suppressive function of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were determined by flow cytometry in blood samples. Levels and in vitro differentiation of Th17 cells were also assessed. Similar levels of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were observed in LSI and HSI patients or controls. However, a positive correlation was detected between sodium intake and levels of CD4+CD25+Foxp3+ Treg cells in SLE and a negative association between CD4+CD69+Foxp3- Treg cells and sodium intake in RA. No other significant associations were detected, including disease activity and sodium intake. Moreover, the suppressor activity of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells was similar in LSI and HSI patients or controls. The levels and in vitro differentiation of Th17 cells were also similar in LSI and HSI individuals. Our results suggest that, in the population studied (Mexican mestizo), the level of sodium intake is not apparently associated with different relevant immune parameters in healthy subjects or patients with SLE or RA.
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Recognition and Management of Pediatric Salt Toxicity.
Blohm, E, Goldberg, A, Salerno, A, Jenny, C, Boyer, E, Babu, K
Pediatric emergency care. 2018;(11):820-824
Abstract
OBJECTIVES Immediate recognition of salt toxicity and aggressive resuscitative measures are critical in the treatment of this lethal poisoning. Despite heroic measures, pediatric deaths due to salt toxicity still occur from irreversible neurological damage. The objective of this article is to review the relevant literature and offer a therapeutic algorithm for the management of pediatric patients presenting with salt toxicity. METHODS A literature search for cases of salt toxicity was conducted. Articles in English that were available electronically through PubMed and Google Scholar were reviewed. RESULTS Nineteen cases and case series of salt toxicity were located using our search strategy. Salt poisoning has a distinct pathophysiology compared with hypernatremia, most notable for the lack of formation of idiogenic osmoles. CONCLUSIONS The approach to treatment differs between salt toxicity and hypernatremia, focusing on rapid correction of serum osmolality rather than gradual normalization of serum sodium concentrations. Consultation of nephrology and child protection services are strongly recommended in the comprehensive treatment approach.