Síndrome de Gitelman: cuándo sospecharlo / Gitelman syndrome, when to suspect it

Las tubulopatías son un grupo heterogéneo de entidades definidas por anomalías de la función tubular renal. El síndrome de Gitelman, objeto de nuestro artículo, está causado por mutaciones inactivantes del gen SLC12A3, que codifica el cotransportador Na-Cl sensible a tiazidas del túbulo contorneado distal, produciendo así una pérdida urinaria de Cl-Na. Se exponen tres casos clínicos de síndrome de Gitelman, cada uno con una clínica de presentación. La finalidad de este artículo es sensibilizar al lector en esta tubulopatía y ayudar en su diagnóstico precoz (AU)

Tubulopathies are a heterogeneous group of entities defined by abnormalities of renal tubular function. Gitelman syndrome, the subject of our article, is caused by inactivating mutations of the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule, thus producing a urinary loss of Cl-Na.Three clinical cases of Gitelman syndrome are presented, each with a clinical presentation. The purpose of this article is to familiarize the reader with this tubulopathy and to help in its early diagnosis. (AU)

Sodium and Potassium Intake, the Sodium to Potassium Ratio, and Associated Characteristics in Older Adults, NHANES 2011-2016.

BACKGROUND: Sodium, potassium, and the balance between these 2 nutrients are associated with hypertension and cardiovascular disease, and prevalence of these conditions increases with age. However, limited information is available on these intakes among older adults. OBJECTIVE: Our aim was to explore the socioeconomic and health factors associated with usual sodium and potassium intakes and the sodium to potassium (Na:K) ratio of older adults. DESIGN: This was a cross-sectional, secondary analysis of the 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey. PARTICIPANTS/SETTING: This study included the data of 5,104 adults 50 years and older, with at least one reliable 24-hour dietary recall and an estimated glomerular filtration rate ≥60 mL/min/1.73 m2. MAIN OUTCOME MEASURES: Sodium and potassium intake, as absolute intake, density (per 1,000 kcal) and ratio of Na:K intake. STATISTICAL ANALYSES: We used t tests and χ2 tests to examine significant differences in intakes on a given day by characteristics. Linear and logistic regression models were used to assess associations of socioeconomic and health characteristics with usual sodium and potassium intakes, determined using the National Cancer Institute method. RESULTS: Only 26.2% of participants consumed <2,300 mg sodium (16.2% of men and 35.2% of women) and 36.0% of men and 38.1% of women consumed at least 3,400 mg and 2,600 mg of potassium, respectively. Fewer than one-third of participants consumed a Na:K ratio of <1.0. Women, those with lower blood pressure, and those with a lower body mass index were more likely to have a ratio <1.0. CONCLUSIONS: Participants consumed too much sodium and not enough potassium, based on current recommendations. A higher Na:K ratio was significantly associated with established risk factors for cardiovascular disease. The study findings suggest that more research on cardiovascular health should include both sodium and potassium, as well as balance between these nutrients.

Short-Term Supplemental Dietary Potassium from Potato and Potassium Gluconate: Effect on Calcium Retention and Urinary pH in Pre-Hypertensive-to-Hypertensive Adults.

Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m2, respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700-800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.

Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort.

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. ß -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.

Feasibility of Low-Sodium, High-Potassium Processed Foods and Their Effect on Blood Pressure in Free-Living Japanese Men: A Randomized, Double-Blind Controlled Trial.

We aimed to verify the effect of new low-sodium high-potassium seasonings and processed foods containing poly-γ-glutamic acid on blood pressure in free-living settings. To this end, we conducted a randomized, double-blind controlled trial on 187 Japanese men, aged 35-67 years, who did not use antihypertensives. Participants were randomly allocated to an intervention (n = 93) or a control group (n = 94). They were given a boxed lunch and miso soup (average Na and K content for the intervention group: 1175 and 1476 mg; for the control group: 2243 and 703 mg, respectively). Blood pressure was measured three times every morning for 1 week immediately before and during the final week of the trial. On the day before and the final day of the intervention period, 24 h urine samples were collected. After intervention, the intervention group showed a significantly stronger decrease in the urinary sodium-to-potassium ratio than the control group (p < 0.001). The mean difference in systolic blood pressure change after adjustment for baseline values between the two groups was -2.1 (95% CI: -3.6, -0.6) mmHg. Compliance between the groups was similar, suggesting successful blinding. In conclusion, the use of new seasonings and processed foods aimed at lowering blood pressure in free-living settings may be feasible and effective.

Analysis and Evaluation of Nutritional Intake and Nutrition Quotient of Korean Athletes with Disabilities in the Tokyo Paralympic Games.

This study analyzed and evaluated the nutritional intake and nutrition quotient for adults (NQ-A) among 21 disabled national athletes preparing for the Tokyo Paralympic competition. A 24-h recall nutrition survey was conducted on the second day of training and one day of the weekend (holidays) to analyze daily nutritional intake. Dietary information was analyzed using the NQ-A questionnaire, which comprises 21 items. The athletes were divided into three groups based on the NQ-A score (High, Middle, Low). A comparative analysis of dietary intake of disabled athletes with the recommended dietary intake amount (RDA) was performed. The intake of carbohydrates (166.9%), proteins (112.3%), vitamin E (112.0%), thiamine (124.6%), riboflavin (100.2%), vitamin B6 (110.6%), vitamin B12 (120.7%), sodium (216.6%), phosphorus (118.3%), iron (146.5%), iodine (143.2%), and selenium (114.2%) was higher than the Korean-recommended amount. In particular, as the results of comparing dietary intake between the three groups showed, the low NQ-A score group had significantly lower intake compared to the %RDA for vitamin E (67.1%), C (26.3%), and Potassium (42.8%). However, with most nutrients, nutritional intake deficiency was not shown to be a problem.

Core Strategies to Increase the Uptake and Use of Potassium-Enriched Low-Sodium Salt.

Excess sodium consumption and insufficient potassium intake contribute to high blood pressure and thus increase the risk of heart disease and stroke. In low-sodium salt, a portion of the sodium in salt (the amount varies, typically ranging from 10 to 50%) is replaced with minerals such as potassium chloride. Low-sodium salt may be an effective, scalable, and sustainable approach to reduce sodium and therefore reduce blood pressure and cardiovascular disease at the population level. Low-sodium salt programs have not been widely scaled up, although they have the potential to both reduce dietary sodium intake and increase dietary potassium intake. This article proposes a framework for a successful scale-up of low-sodium salt use in the home through four core strategies: availability, awareness and promotion, affordability, and advocacy. This framework identifies challenges and potential solutions within the core strategies to begin to understand the pathway to successful program implementation and evaluation of low-sodium salt use.

Sodium and Potassium Excretion of Schoolchildren and Relationship with Their Family Excretion in China.

This cross-sectional study aimed to assess 24-h urinary sodium and potassium excretion in children and the relationships with their family excretion. Using the baseline data of a randomized trial conducted in three cities of China in 2018, a total of 590 children (mean age 8.6 ± 0.4 years) and 1180 adults (mean age 45.8 ± 12.9 years) from 592 families had one or two complete 24-h urine collections. The average sodium, potassium excretion and sodium-to-potassium molar ratio of children were 2180.9 ± 787.1 mg/d (equivalent to 5.5 ± 2.0 g/d of salt), 955.6 ± 310.1 mg/d and 4.2 ± 1.7 respectively, with 77.1% of the participants exceeding the sodium recommendation and 100% below the proposed potassium intake. In mixed models adjusting for confounders, every 1 mg/d increase in sodium excretion of adult family members was associated with a 0.11 mg/d (95% CI: 0.06 to 0.16, p < 0.0001) increase in sodium excretion of children. The family-child regression coefficient corresponds to 0.20 mg/d (95% CI: 0.15 to 0.26, p < 0.0001) per 1 mg/d in potassium and to 0.36 (95% CI: 0.26 to 0.45, p < 0.0001) in sodium-to-potassium molar ratio. Children in China are consuming too much sodium and significantly inadequate potassium. The sodium, potassium excretion and sodium-to-potassium ratio of children are associated with their family excretions in small to moderate extent. Efforts are warranted to support salt reduction and potassium enhancement in children through comprehensive strategies engaging with families, schools and food environments.

Short-Term RCT of Increased Dietary Potassium from Potato or Potassium Gluconate: Effect on Blood Pressure, Microcirculation, and Potassium and Sodium Retention in Pre-Hypertensive-to-Hypertensive Adults.

Increased potassium intake has been linked to improvements in cardiovascular and other health outcomes. We assessed increasing potassium intake through food or supplements as part of a controlled diet on blood pressure (BP), microcirculation (endothelial function), and potassium and sodium retention in thirty pre-hypertensive-to-hypertensive men and women. Participants were randomly assigned to a sequence of four 17 day dietary potassium treatments: a basal diet (control) of 60 mmol/d and three phases of 85 mmol/d added as potatoes, French fries, or a potassium gluconate supplement. Blood pressure was measured by manual auscultation, cutaneous microvascular and endothelial function by thermal hyperemia, utilizing laser Doppler flowmetry, and mineral retention by metabolic balance. There were no significant differences among treatments for end-of-treatment BP, change in BP over time, or endothelial function using a mixed-model ANOVA. However, there was a greater change in systolic blood pressure (SBP) over time by feeding baked/boiled potatoes compared with control (-6.0 mmHg vs. -2.6 mmHg; p = 0.011) using contrast analysis. Potassium retention was highest with supplements. Individuals with a higher cardiometabolic risk may benefit by increasing potassium intake. This trial was registered at ClinicalTrials.gov as NCT02697708.

Geospatial Analysis of Sodium and Potassium Intake: A Swiss Population-Based Study.

Inadequate sodium and potassium dietary intakes are associated with major, yet preventable, health consequences. Local public health interventions can be facilitated and informed by fine-scale geospatial analyses. In this study, we assess the existence of spatial clustering (i.e., an unusual concentration of individuals with a specific outcome in space) of estimated sodium (Na), potassium (K) intakes, and Na:K ratio in the Bus Santé 1992-2018 annual population-based surveys, including 22,495 participants aged 20-74 years, residing in the canton of Geneva, using the local Moran's I spatial statistics. We also investigate whether socio-demographic and food environment characteristics are associated with identified spatial clustering, using both global ordinary least squares (OLS) and local geographically weighted regression (GWR) modeling. We identified clear spatial clustering of Na:K ratio, Na, and K intakes. The GWR outperformed the OLS models and revealed spatial variations in the associations between explanatory and outcome variables. Older age, being a woman, higher education, and having a lower access to supermarkets were associated with higher Na:K ratio, while the opposite was seen for having the Swiss nationality. Socio-demographic characteristics explained a major part of the identified clusters. Socio-demographic and food environment characteristics significantly differed between individuals in spatial clusters of high and low Na:K ratio, Na, and K intakes. These findings could guide prioritized place-based interventions tailored to the characteristics of the identified populations.

Advances in Genomics Research of Blood Pressure Responses to Dietary Sodium and Potassium Intakes.

More than half of US adults have hypertension by 40 years of age and a subsequent increase in atherosclerotic cardiovascular disease risk. Dietary sodium and potassium are intricately linked to the pathophysiology of hypertension. However, blood pressure responses to dietary sodium and potassium, phenomena known as salt and potassium sensitivity of blood pressure, respectively, are heterogenous and normally distributed in the general population. Like blood pressure, salt and potassium sensitivity are complex phenotypes, and previous research has shown that up to 75% of individuals experience a blood pressure change in response to such dietary minerals. Previous research has also implicated both high salt sensitivity and low salt sensitivity (or salt resistance) of blood pressure to an increased risk of hypertension and potentially atherosclerotic cardiovascular disease risk. Given the clinical challenges required to accurately measure the sodium and potassium response phenotypes, genomic characterization of these traits has become of interest for hypertension prevention initiatives on both the individual and population levels. Here, we review advances in human genomics research of blood pressure responses to dietary sodium and potassium by focusing on 3 main areas, including the phenotypic characterization of salt sensitivity and resistance, clinical challenges in diagnosing such phenotypes, and the genomic mechanisms that may help to explain salt and potassium sensitivity and resistance. Through this process, we hope to further underline the value of leveraging genomics and broader multiomics for characterizing the blood pressure response to sodium and potassium to improve precision in lifestyle approaches for primordial and primary atherosclerotic cardiovascular disease prevention.

Modelling the Cost-Effectiveness of Implementing a Dietary Intervention in Renal Transplant Recipients.

BACKGROUND: The Dietary Approach to Stop Hypertension (DASH) and potassium supplementation have been shown to reduce the risk of death with a functioning graft (DWFG) and renal graft failure in renal transplant recipients (RTR). Unfortunately, a key problem for patients is the adherence to these diets. The aim of this study is to evaluate the cost-effectiveness and budget impact of higher adherence to either the DASH or potassium supplementation. METHODS: A Markov model was used to simulate the life course of 1000 RTR in the Netherlands. A societal perspective with a lifetime time horizon was used. The potential effect of improvement of dietary adherence was modelled in different scenarios. The primary outcomes are the incremental cost-effectiveness ratio (ICER) and the budget impact. RESULTS: In the base case, improved adherence to the DASH diet saved 27,934,786 and gained 1880 quality-adjusted life years (QALYs). Improved adherence to potassium supplementation saved €1,217,803 and gained 2901 QALYs. Both resulted in dominant ICERs. The budget impact over a five-year period for the entire Dutch RTR population was €8,144,693. CONCLUSION: Improving dietary adherence in RTR is likely to be cost-saving and highly likely to be cost-effective compared to the current standard of care in the Netherlands.

An in vivo protein landscape of the mouse DCT during high dietary K+ or low dietary Na+ intake.

The hormone aldosterone is essential for maintaining K+ and Na+ balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K+ diet. Many of these changes were not detectable by analyzing whole kidney samples from the same animals. When comparing responses to high-K+ versus low-Na+ diets, protein translation, chaperone-mediated protein folding, and protein ubiquitylation were likely to be significantly altered in the DCT subsequent to a high-K+ diet. In conclusion, this study defines an in vivo protein landscape of the DCT in male mice following either a low-NaCl or a high-K+ diet and acts as an essential resource for the kidney research community.NEW & NOTEWORTHY The mineralocorticoid aldosterone, essential for maintaining body K+ and Na+ balance, has different effects if secreted due to hypovolemia or hyperkalemia. Here, we used proteomics to profile kidney distal convoluted tubule (DCT) cells isolated by a novel FACS approach from mice fed a low-Na+ diet (mimicking hypovolemia) or a high-K+ diet (mimicking hyperkalemia). The study provides the first in-depth proteome of the mouse DCT and insights into how it is physiologically regulated.

Potassium chloride-based replacers: modeling effects on sodium and potassium intakes of the US population with cross-sectional data from NHANES 2015-2016 and 2009-2010.

BACKGROUND: Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce sodium intake. OBJECTIVE: The purpose of this study was to quantitatively estimate changes in intakes of sodium and potassium by the US population assuming use of potassium-based NaCl replacers in top dietary sodium sources. METHODS: Data collected in the What We Eat in America (WWEIA) component of the 2015-2016 and 2009-2010 NHANES were used to identify top-ranking sources of dietary sodium among the population aged 2 y and older based on contributions from food categories aligning with the FDA draft guidance for voluntary sodium reduction. Predicted nutrient intakes were estimated in models assuming total and feasible and practical (F&P) replacement of added NaCl with KCl in foods and ingredients within the top food sources of sodium. An expert elicitation was conducted to collect information on the F&P KCl replacement of added NaCl. RESULTS: Using 2015-2016 consumption data, the total replacement of added NaCl with KCl in the 18 top-ranking sources of dietary sodium results in a predicted sodium intake of 2004 mg/d from the replacement of 1406 mg/d sodium with 1870 mg/d potassium as KCl. Modeled F&P replacement predicted sodium intakes of 3117 mg/d (range of 2953 to 3255 mg/d) from the replacement of 294 mg/d sodium (155 to 457 mg/d) with 390 mg/d potassium (206 to 608 mg/d). Similar results are seen with 2009-2010 data. CONCLUSIONS: The F&P replacement of NaCl with KCl in top-ranking sources of dietary sodium modeled in this study can result in decreased sodium to a level consistent with the short-term intake goal targeted by the FDA of 3000 mg/d, with the mean potassium intake remaining in the range recommended for the apparently healthy population.

Potassium deficiency decreases the capacity for urea synthesis and markedly increases ammonia in rats.

Our study provides novel findings of experimental hypokalemia reducing urea cycle functionality and thereby severely increasing plasma ammonia. This is pathophysiologically interesting because plasma ammonia increases during hypokalemia by a hitherto unknown mechanism, which may be particular important in relation to the unexplained link between hypokalemia and hepatic encephalopathy. Potassium deficiency decreases gene expression, protein synthesis, and growth. The urea cycle maintains body nitrogen homeostasis including removal of toxic ammonia. Hyperammonemia is an obligatory trait of liver failure, increasing the risk for hepatic encephalopathy, and hypokalemia is reported to increase ammonia. We aimed to clarify the effects of experimental hypokalemia on the in vivo capacity of the urea cycle, on the genes of the enzymes involved, and on ammonia concentrations. Female Wistar rats were fed a potassium-free diet for 13 days. Half of the rats were then potassium repleted. Both groups were compared with pair- and free-fed controls. The following were measured: in vivo capacity of urea-nitrogen synthesis (CUNS); gene expression (mRNA) of urea cycle enzymes; plasma potassium, sodium, and ammonia; intracellular potassium, sodium, and magnesium in liver, kidney, and muscle tissues; and liver sodium/potassium pumps. Liver histology was assessed. The diet induced hypokalemia of 1.9 ± 0.4 mmol/L. Compared with pair-fed controls, the in vivo CUNS was reduced by 34% (P < 0.01), gene expression of argininosuccinate synthetase 1 (ASS1) was decreased by 33% (P < 0.05), and plasma ammonia concentrations were eightfold elevated (P < 0.001). Kidney and muscle tissue potassium contents were markedly decreased but unchanged in liver tissue. Protein expressions of liver sodium/potassium pumps were unchanged. Repletion of potassium reverted all the changes. Hypokalemia decreased the capacity for urea synthesis via gene effects. The intervention led to marked hyperammonemia, quantitatively explainable by the compromised urea cycle. Our findings motivate clinical studies of patients with liver disease.

Hypokalemia in peritoneal dialysis patients in Thailand: the pivotal role of low potassium intake.

OBJECTIVE: Hypokalemia is highly prevalent in chronic peritoneal dialysis (PD) patients worldwide, particularly in Thailand. This study aims to investigate the major determinants of hypokalemia in Thai PD patients. METHODS: A cross-sectional study was performed in chronic PD patients at 4 PD centers in Bangkok, Thailand. Hypokalemia was defined if the average serum potassium level during the last 3 consecutive visits was < 3.5 mEq/L. Patients and/or their caregivers were asked to perform a 3-day dietary food record and take pre- and post-meal pictures following the instructed protocol. Daily dietary nutrients, including potassium, were estimated by a single dietician using INMUCAL-N software. Total potassium excretion was determined by 24-h PD effluents and urine collection. Intracellular and extracellular water values (ICW and ECW, respectively) were measured by electrical bioimpedance assay (BIA) to indirectly explore the role of intracellular potassium shift in hypokalemia. RESULTS: Among 60 eligible PD patients, 19 (31%) had hypokalemia. Hypokalemic patients had significantly lower dietary potassium intake (24.4 ± 11.1 vs. 30.5 ± 9.4 mEq/day, p = 0.031) and lower total potassium excretion (28.5 ± 8.4 vs. 36.7 ± 11.2 mEq/day, p = 0.006) compared to normokalemic patients. Both groups had comparable values of ICW and ECW. On logistic regression, there was no significant correlation between hypokalemia and daily PD exchange volume, total Kt/Vurea, residual renal function, concurrent medications (insulin, diuretics, renin-angiotensin-aldosterone inhibitor, and beta-blockers) or ICW. Low dietary potassium was an independent risk factor for hypokalemia. CONCLUSION: Low dietary potassium intake, rather than increased potassium excretion or intracellular shift, is the major contributing factor of hypokalemia in Thai chronic PD patients. Dietary intervention or potassium supplement protocol should be implemented.

Kcnj16 knockout produces audiogenic seizures in the Dahl salt-sensitive rat.

Kir5.1 is an inwardly rectifying potassium (Kir) channel subunit abundantly expressed in the kidney and brain. We previously established the physiologic consequences of a Kcnj16 (gene encoding Kir5.1) knockout in the Dahl salt-sensitive rat (SSKcnj16-/-), which caused electrolyte/pH dysregulation and high-salt diet-induced mortality. Since Kir channel gene mutations may alter neuronal excitability and are linked to human seizure disorders, we hypothesized that SSKcnj16-/- rats would exhibit neurological phenotypes, including increased susceptibility to seizures. SSKcnj16-/- rats exhibited increased light sensitivity (fMRI) and reproducible sound-induced tonic-clonic audiogenic seizures confirmed by electroencephalography. Repeated seizure induction altered behavior, exacerbated hypokalemia, and led to approximately 38% mortality in male SSKcnj16-/- rats. Dietary potassium supplementation did not prevent audiogenic seizures but mitigated hypokalemia and prevented mortality induced by repeated seizures. These results reveal a distinct, nonredundant role for Kir5.1 channels in the brain, introduce a rat model of audiogenic seizures, and suggest that yet-to-be identified mutations in Kcnj16 may cause or contribute to seizure disorders.

Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study.

BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

Associations of sodium and potassium consumption with the gut microbiota and host metabolites in a population-based study in Chinese adults.

BACKGROUND: There is increasing evidence that sodium consumption alters the gut microbiota and host metabolome in murine models and small studies in humans. However, there is a lack of population-based studies that capture large variations in sodium consumption as well as potassium consumption. OBJECTIVE: We examined the associations of energy-adjusted dietary sodium (milligrams/kilocalorie), potassium, and sodium-to-potassium (Na/K) ratio with the microbiota and plasma metabolome in a well-characterized Chinese cohort with habitual excessive sodium and deficient potassium consumption. METHODS: We estimated dietary intakes from 3 consecutive validated 24-h recalls and household inventories. In 2833 adults (18-80 y old, 51.2% females), we analyzed microbial (genus-level 16S ribosomal RNA) between-person diversity, using distance-based redundancy analysis (dbRDA), and within-person diversity and taxa abundance using linear regression, accounting for geographic variation in both. In a subsample (n = 392), we analyzed the overall metabolome (dbRDA) and individual metabolites (linear regression). P values for specific taxa and metabolites were false discovery rate adjusted (q-value). RESULTS: Sodium, potassium, and Na/K ratio were associated with microbial between-person diversity (dbRDA P < 0.01) and several specific taxa with large geographic variation, including pathogenic Staphylococcus and Moraxellaceae, and SCFA-producing Phascolarctobacterium and Lachnospiraceae (q-value < 0.05). For example, sodium and Na/K ratio were positively associated with Staphylococcus and Moraxellaceae in Liaoning, whereas potassium was positively associated with 2 genera from Lachnospiraceae in Shanghai. Additionally, sodium, potassium, and Na/K ratio were associated with the overall metabolome (dbRDA P ≤ 0.01) and several individual metabolites, including butyrate/isobutyrate and gut-derived phenolics such as 1,2,3-benzenetriol sulfate, which was negatively associated with sodium in Guizhou (q-value < 0.05). CONCLUSIONS: Our findings suggest that sodium and potassium consumption is associated with taxa and metabolites that have been implicated in cardiometabolic health, providing insights into the potential roles of gut microbiota and host metabolites in the pathogenesis of sodium- and potassium-associated diseases. More studies are needed to confirm our results.

Top Food Category Contributors to Sodium and Potassium Intake - United States, 2015-2016.

Most U.S. adults consume too much sodium and not enough potassium (1,2). For apparently healthy U.S. adults aged ≥19 years, guidelines recommend reducing sodium intake that exceeds 2,300 mg/day and consuming at least 3,400 mg/day of potassium for males and at least 2,600 mg/day for females* (1). Reducing population-level sodium intake can reduce blood pressure and prevent cardiovascular diseases, the leading causes of death in the United States (1,3). Adequate potassium intake might offset the hypertensive effects of excessive sodium intake (1). Data from the 2015-2016 What We Eat in America (WWEIA) dietary interview component of the National Health and Nutrition Examination Survey (NHANES)† were analyzed to identify top food categories contributing to sodium and potassium intake for U.S. residents aged ≥1 year. During 2015-2016, 40% of sodium consumed came from the top 10 food categories, which included prepared foods with sodium added (e.g., deli meat sandwiches and pizza). Approximately 43% of potassium consumed was from 10 food categories, which included foods naturally low in sodium (e.g., unflavored milk, fruit, vegetables) and prepared foods. These results can inform efforts to encourage consumption of foods naturally low in sodium, which might have the dual benefit of reducing sodium intake and increasing potassium intake, contributing to cardiovascular disease prevention.