Urinary Potassium Excretion Research Articles

Abstract P207: Blood Metabolomic Signatures of 24-hr Urinary Sodium and Potassium Excretion Were Associated With Cardiometabolic Diseases in the Hispanic Community Health Study/Study of Latinos

Background: 24hr urinary sodium (Na) potassium (K) excretions are considered as accurate measures of sodium and potassium intake, but data are limited in large population-based studies due to the difficulties of 24hr urine sample collection. Hypothesis: 24hr urinary Na and K excretion can be predicated by blood metabolomic signatures, which are associated with the risk of cardiometabolic diseases. Methods: We assessed 24hr urinary Na, K excretion and sodium/potassium ratio (Na/K) in 447 apparently healthy individuals from the SOL-Nutrition & Physical Activity Assessment Study (SOLNAS) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We calculated urinary Na, K excretion, and Na/K metabolite scores by using the Least Absolute Shrinkage and Selection Operator regression on 199 serum metabolites in SOLNAS, and evaluated their associations with incident CVD (heart failure, stroke, myocardial infarction), type 2 diabetes (T2D), and hypertension (HTN) in up to 5738 individuals in HCHS/SOL. Results: There were 41, 22, and 71 metabolites selected to be predictive of urinary Na, K excretion, and Na/K, respectively. Metabolite scores were significantly correlated with measured urinary Na (r=0.35, p < 5e -14 ), K (r=0.58, p< 5e -50 ) excretion and Na/K (r=0.6, p< 5e -50 ). After multivariate adjustment, metabolite scores of urinary Na excretion and Na/K were significantly associated with incident CVD risk (hazard ratio=2.6 for Na and 1.91 for Na/K, per 1 SD increase in score), incident T2D (relative risk [RR]=1.33 for Na and 1.16 for Na/K), and incident HTN (RR=1.53 for Na and 1.35 for Na/K) over a median 7.6 years of follow-up. The metabolite score of urinary K excretion was not associated with CMD risk. Conclusion: In US Hispanics/Latinos, higher levels of 24hr urinary Na excretion and Na/K indicated by blood metabolomics signatures were associated with increased risk of CVD, HTN, and T2D.

Abstract P419: Urinary Na:K Excretion and the Risk of Cardiovascular Events in Patients With Chronic Kidney Disease

Introduction: The risk of death from cardiovascular disease (CVD) is three times higher in patients with chronic kidney disease (CKD). Urine sodium and potassium excretion are altered in CKD and have been identified as CVD risk factors in other populations; therefore, they may represent therapeutic targets in persons with CKD. We aimed to examine the association between the ratio of urine Na-to-K (Na:K) with incident atrial fibrillation (AF), heart failure (HF), and myocardial infarction (MI) in patients with CKD. Methods: 2341 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort free of CVD at study entry. Spot urinary Na:K ratio was measured from 24-hour collections and divided into quartiles. Outcomes included physician-adjudicated hospitalizations for AF, MI and HF (overall, preserved [HFpEF] and reduced ejection fraction [HFrEF]). Incidence rates (with 95% CI) were calculated per 1000 person-years. We performed Cox regression in a series of nested models, adjusting for demographics, habits, baseline comorbidities, kidney function and concurrent medications. Results: 586 participants were in the highest quartile of urinary Na:K excretion (mean age 54.3 (SD 11.7); 46% women (271 out of 586). Mean eGFR was lower in this group [49.5 (SD 19.4)] and 24-hour urine protein was higher [0.27 (IQR 0.08-1.19)] compared to lower quartiles. Rates of incident HF [18 (95% CI 7.5-12.5)] and MI [10 (95% CI 7.5-12.5)] were higher in persons with higher urine Na:K ratio (Fig 1). In adjusted models, the highest quartile (compared with the lowest quartile) of urine Na:K ratio was associated with AF (1.57, 95% CI 1.08-2.3) and HF (1.43, 95% CI 1.15-4.12). In sensitivity analyses, elevated urine Na:K was significantly associated with HFrEF (2.18, 95% CI in 1.15-4.12), but not HFpEF. Conclusions: Urinary Na:K excretion was associated with an increased incidence of atrial fibrillation and heart failure in persons with CKD free of CVD. Sodium and potassium represent possible modifiable risk factors for CVD prevention in patients with CKD.

Urinary and fecal potassium excretion prediction in dairy cattle: A meta-analytic approach

Quantification of potassium (K) excretion in dairy cattle is important to understand the environmental impact of dairy farming. To improve and monitor the environmental impact of dairy cows, there is a need for a simple, inexpensive, and less laborious method to quantify K excretion on dairy farms. The adoption of empirical mathematical models has been shown to be a promising tool to address this issue. Thus, the current study aimed to develop empirical predictive models for K excretion in dairy cattle from urine and feces that can help evaluate efficiency and monitor the environmental impact of milk production. To develop urine K (KUr, g/d) and fecal K (KFa, g/d) excretion prediction models, published literature that involved 45 and 54 treatment means from 10 and 14 studies, respectively, were used. Some studies reported either urinary or fecal K excretion or both, but in total, treatment means used to develop the models were from 17 studies. The linear mixed models were fitted with the fixed effect of K intake, DMI, dietary K content, urine volume, milk yield, and water intake, and the random effect of study weighted according to the number of observations. Leave-one-study out cross-validation was used to evaluate the performance of the proposed models and the best model was based on the lowest root mean square prediction error as a percentage of the observed mean values (RMSPE%) and highest concordance correlation coefficient (CCC). As expected, most daily K excretion was through urine (202.5 ± 92.1 g/d) than through feces (43.5 ± 21.0 g/d), and among the proposed models, the model including dietary K concentration showed poor predictive ability for both KUr and KFa with the lowest CCC values (−0.15 and −0.02, respectively) and systematic bias. The model developed using DMI to predict KFa excretion showed reasonable accuracy, as indicated by RMSPE, CCC, and R2marginal of 46.6%, 0.42, and 48%, respectively. Among the proposed models for KUr and KFa, the model with K intake demonstrated better predictive performance, showing minimal systematic bias and random errors due to data variability of >92%. While these proposed models suggested that reducing K intake can lead to a decrease in K excretion, it is important to ensure that dairy cows receive adequate amounts of this nutrient to maintain optimal health and productivity, especially during periods of heat stress.

Effects of Reduced Dietary Sodium and the DASH Diet on GFR: The DASH-Sodium Trial.

A potassium-rich DASH diet combined with low sodium reduces blood pressure. However, the effects of sodium reduction in combination with the DASH diet on kidney function are unknown. We aimed to determine the effects of sodium reduction and the DASH diet, on estimated glomerular filtration rate (eGFR) by cystatin C. DASH-Sodium was a controlled, feeding study in adults with elevated or stage 1 hypertension, randomly assigned to the DASH or a control diet. On their assigned diet, participants consumed each of three sodium levels for 30 days following a 2-week run-in period of a high sodium-control diet. The three sodium levels were low (50 mmol/d), medium (100 mmol/d), and high (150 mmol/d). The primary outcome was change in eGFR based on cystatin C. Cystatin C was measured in 409 of the original 412 participants of which 207 were assigned the DASH diet and 202 to the control diet. Compared with control, the DASH diet did not affect eGFR (β=-0.96 mL/min/1.73 m2; 95%CI: -2.74, 0.83). In contrast, low versus high sodium intake decreased eGFR (β=-2.36 mL/min/1.73 m2; 95%CI: -3.64, -1.07). Together, compared to the high sodium-control diet, the low sodium-DASH diet decreased eGFR by 3.10 mL/min/1.73 m2 (95%CI: -5.46, -0.73). This effect was attenuated with adjustment for diastolic blood pressure and 24-hr urinary potassium excretion. A combined low sodium-DASH diet reduced eGFR over a 4-week period. Future research should focus on the impact of these dietary interventions on subclinical kidney injury and their long-term impact on progression to chronic kidney disease.

Urinary Biomarkers in Screening for the Usual Intake of Fruit and Vegetables, and Sodium, Potassium, and the Sodium-to-Potassium Ratio: Required Number and Accuracy of Measurements.

Because of within-individual variation, surveys to estimate an individual's usual food intake must be conducted over many days, in general. Here, using non-invasive biomarkers, we examined the number of measurements required to screen for the usual intake of fruit and vegetables, in addition to sodium, potassium, and the sodium-to-potassium (Na/K) ratio. Participants were 202 subjects aged 40-74 years from five areas of Japan who completed weighed food records (WFR) and five 24-hour urinary collections (24-h UCs) between 2012 and 2013. The number of 24-h UCs required to screen for intake that deviated from guidelines estimated by the WFR and their accuracies were assessed by the area under the curve (AUC) in a receiver-operating characteristics (ROC) analysis. The single urinary excretion of sodium, potassium, and the Na/K ratio showed moderate performance (AUC value: >0.7) in discriminating deviations from their criteria by respective intake based on the WFR. Urinary potassium excretion also showed moderate performance (AUC value: >0.7) in estimating the intake of vegetables but could not be used to estimate fruit intake even after five collections. The non-invasive measurement of biomarkers in a single 24-h UC showed moderate performance in screening the usual intake of vegetables, as measured based on the 12-day WFR, as well as of sodium, potassium, and the Na/K ratio.

Low urinary sodium-to-potassium ratio in the early phase following single-unit cord blood transplantation is a predictive factor for poor non-relapse mortality in adults

Although daily higher urinary sodium (Na) and potassium (K) excretion ratio is associated with the risk of cardiovascular disease in the general population, a low Na/K ratio is associated with renal dysfunction in critically ill patients. Thus, we retrospectively analyzed the impact of daily urinary Na and K excretion and their ratio on non-relapse mortality (NRM) and overall mortality in 172 adult single-unit cord blood transplantation (CBT) patients treated at our institution between 2007 and 2020. Multivariate analysis showed that a low urinary Na/K ratio at both 14 days (hazard ratio [HR], 4.82; 95% confidence interval [CI], 1.81–12.83; P = 0.001) and 28 days (HR, 4.47; 95% CI 1.32–15.12; P = 0.015) was significantly associated with higher NRM. Furthermore, a low urinary Na/K ratio at 28 days was significantly associated with higher overall mortality (HR, 2.38; 95% CI 1.15–4.91; P = 0.018). Patients with a low urinary Na/K ratio had decreased urine volume, more weight gain, experienced more grade III–IV acute graft-versus-host disease, and required corticosteroids by 28 days after CBT. These findings indicate that a low urinary Na/K ratio early after single-unit CBT is associated with poor NRM and survival in adults.

Clinical Features and Unusual Heterozygous Mutations in Patients with Renal Hypokalemia.

Renal hypokalemia is associated with mutation. This study aimed to investigate the clinical features and pathogenic mutations in patients with renal hypokalemia. The patients with hypokalemia were enrolled, and the renal function, thyroid function, renin-aldosterone system, urinary potassium excretion, and exome sequencing were performed. The correlation between the clinical phenotypes and causative genes was assessed. Five patients with hypokalemia were enrolled and diagnosed as tubular hypokalemia. The patients with common clinical manifestations were difficult to differentiate based on atypical laboratory findings. The results of the genetic analysis were as follows: both patient 1 and patient 2 were heterozygous for the c.C625T mutation of the KCNJ1 gene, which is responsible for Bartter syndrome. Patient 3 was heterozygous for the c.G298A mutation of the ATP6V1B1 gene, which is responsible for renal tubular acidosis. Patient 4 had a compound heterozygous mutation of c.G893A of the BSND gene, responsible for Bartter syndrome, and c.1029+5G>A, the ATP6V0A4 gene responsible for distal renal tubular acidosis. Patient 5 had Gitelman syndrome and carried the compound heterozygous mutations c.C1963T and c.G2029A of the SLC12A3 gene. All the above loci were known heterozygous mutations. The unusual heterozygous mutations were identified in five renal hypokalemia patients. Molecular diagnosis of tubular hypokalemia was conducive to accurate diagnosis and treatment.

Simultaneous Occurrence of Hyponatremia and Hypokalemia in a Patient with Herpes Zoster: A Case Report with a Review of the Literature.

We herein report a patient with herpes zoster (HZ), severe hyponatremia, and hypokalemia. Syndrome of inappropriate antidiuresis (SIAD) leads to euvolemic hyponatremia and hypoosmotic plasma due to inadequate diuresis. Hyponatremia in the current patient was caused by SIAD and associated with HZ of the trigeminal facial nerve (V1). The patient also had hypokalemia, with excessive urinary potassium excretion and elevated cortisol levels. Hypokalemia is caused by hypercortisolemia, which is stimulated by HZ pain. Adequate treatment for HZ and comprehensive pain control play pivotal roles in improving SIAD, cortisol hypersecretion, and the subsequent electrolyte abnormalities.

Estimation of 24-hour urinary sodium and potassium excretion among Chinese adults: a cross-sectional study from the China National Nutrition Survey

BackgroundHigh-sodium intake is one of the most important risk factors for hypertension and cardiovascular disease, yet reliable national estimates of sodium intake in Chinese adults have not been reported. ObjectivesWe estimated 24-h urinary sodium and potassium excretion and population daily sodium and potassium intake of Chinese adults for the first time at a national level. MethodsA nationally representative cross-sectional survey was conducted to collect 24-h urine specimens from Chinese adults aged ≥18 y as part of the China National Nutrition Survey 2015. Finally, 10,114 participants (4932 males and 5182 females) with complete 24-h urine specimens were included in the analysis. Estimates of mean urinary electrolyte excretion and demographic, socioeconomic, and health characteristics were used with weighted coefficients that accounted for sample selection probabilities, poststratification weighting, and nonresponse rates. ResultsThe estimation of overall weighted mean 24-h urinary sodium excretion was 4121 mg (95% confidence interval [CI]: 3993, 4250), 4155 mg (95% CI: 3993, 4317) in males and 4081 mg (95% CI: 3953, 4209) in females (P for sex difference = 0.36). Overall mean 24-h urinary potassium excretion was 1534 mg (95% CI: 1492, 1577), 1468 mg (95% CI: 1424, 1513) in males and 1614 mg (95% CI: 1569–1660) in females (P for sex difference <0.001). Mean 24-h urinary sodium excretion was significantly higher in rural adults (4350 mg; 95% CI: 4217, 4483) than in urban residents (3909 mg; 95% CI: 3739, 4080; P < 0.001), and in northern residents (4388 mg; 95% CI: 4237, 4539) than in southern residents (3998 mg; 95% CI: 3832, 4163; P = 0.002). ConclusionsThe first nationwide survey with 24-h urine collection confirmed that mean sodium intake in Chinese adults was more than twice the upper limit, whereas mean potassium intake was <60% of the lower limit, recommended by the World Health Organization. Urgent measures should be taken to reduce sodium intake and increase potassium intake in China.

Higher Nocturnal Blood Pressure and Blunted Nocturnal Dipping Are Associated With Decreased Daytime Urinary Sodium and Potassium Excretion in Patients With CKD

Sodium homeostasis is intimately associated with blood pressure (BP) rhythm, and potassium excretion is closely associated with sodium excretion in the general population. However, the association between circadian sodium and potassium pattern excretion and nocturnal BP in patients with chronic kidney disease (CKD) is not elucidated. We evaluated the correlation between the day-to-night ratio of urinary sodium and potassium excretion rate, nocturnal blood pressure, and nocturnal BP dipping in a CKD cohort. A total of 3152 (56.76% males, mean age 47.63 years) individuals with CKD were included in the study. Patients in quartile 1 (with the lowest ratio) exhibited a 12 mmHg or 9 mmHg higher nocturnal systolic blood pressure (SBP) and blunted SBP dipping than those in quartile 4 when urinary sodium or potassium excretion rate was divided into day-to-night ratios (both P< 0.001). In multivariate analyses, lower day-to-night ratio of urinary sodium was independently linked to higher nocturnal SBP and blunted SBP dipping (linear regression coefficient (95% confidence interval [CI]):-6.89 (-9.48 to-4.31), and-3.64 (-5.48 to-1.80), respectively; both P< 0.001). Similarly, compared with the highest quartile of day-to-night ratio of urinary potassium excretion rate, linear regression coefficient (95% CI) for the lowest quartile was-5.60 (-8.13 to-3.07) for nocturnal SBP, and-2.47 (-4.28 to-0.67) for SBP dipping (both P< 0.001). Moreover, urine flow rate and concentrates of sodium or potassium in the urine were positively associated with urinary sodium or potassium excretion during daytime (P< 0.001). A higher nocturnal BP and a blunted nocturnal BP dipping were both independently linked to a lower excretion of sodium or potassium during the day in patients with CKD. Furthermore, a decreased urine flow rate and a diminished capacity to concentrate sodium or potassium in the urine appear to be the key contributors to a low day-to-night ratio of urinary sodium excretion or potassium rate.

Sodium and potassium consumption in Jamaica: National estimates and associated factors from the Jamaica Health and Lifestyle Survey 2016-2017.

This study aimed to estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. A cross-sectional study was conducted using data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were noninstitutionalized Jamaicans aged ≥15 years. Trained staff collected sociodemographic and health data via interviewer-administered questionnaires and spot urine samples. The Pan American Health Organization formula was used to estimate 24-hour urine sodium and potassium excretion. High sodium level was defined as ≥2000 mg/day, and low potassium levels as <3510 mg/day (World Health Organization criteria). Associations between these outcomes and sociodemographic and clinical characteristics were explored using multivariable ANOVA models using log-transformed 24-hour urine sodium and potassium as outcome variables. Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). The mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, P < .001). The mean potassium excretion was 2052 mg/day (males, 2210 mg/day; females, 1904 mg/day; P = .001). The prevalence of high sodium consumption was 66.6% (males 72.8%, females 60.7%, P < .001) and that of low potassium intake was 88.8% (85.1% males, 92.3% females, P < .001). Sodium consumption was inversely associated with older age, higher education, and low glomerular filtration rate but was directly associated with being male, current smoking, and obesity. Overall, males had higher sodium consumption than women, with the effect being larger among hypertensive men. Women with hypertension had lower sodium consumption than nonhypertensive women; however, hypertensive men had higher sodium consumption than nonhypertensive men. Potassium consumption was higher among men, persons with obesity, and those with high total cholesterol but was lower among men with "more than high school" education compared to men with "less than high school" education. We conclude that most Jamaican adults have diets high in sodium and low in potassium. In this study, sodium consumption was directly associated with male sex, obesity, and current smoking but was inversely associated with older age and higher education. High potassium consumption was associated with obesity and high cholesterol levels. These associations should be further explored in longitudinal studies and population-based strategies should be developed to address these cardiovascular risk factors.

THU599 Serum And Urinary Free Cortisone As Novel Predictor Of Low-renin Arterial Hypertension

Abstract Disclosure: A. Tapia-Castillo: None. J. Perez: None. A. Sandoval: None. F. Allende: None. S. Solari: None. C.E. Fardella: None. C. Carvajal: None. A large proportion of low-renin hypertensive (LRH) patients correspond to primary aldosteronism (PA) caused by excessive MR activation mediated by excess of aldosterone. However, some of these LRH patients have low to normal serum aldosterone levels, where is thought the MR activation is aldosterone-independent and more likely due to glucocorticoid-mediated MR activation, as occurs in the nonclassical apparent mineralocorticoid excess (NCAME), which is characterized by high cortisol/cortisone ratio and low cortisone, affecting not only blood pressure (BP) control and urinary potassium excretion but also causing cardiac and renal damage, endothelial dysfunction and subclinical inflammation. Objective: To evaluate cortisone as a predictor of LRH and its association with parameters of kidney and vascular damage. Design: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low-renin phenotype (plasma renin activity (PRA) &amp;lt;1ng/ml*h) and low serum cortisone (&amp;lt;p25th). We measured clinical, biochemical, renal and vascular parameters. Statistical analyses as group comparisons were performed by Mann Whitney, and discriminatory analyses by ROC curves. Results: We identified 43% of subjects with low-renin phenotype. PRA was associated with serum aldosterone (r=0.36; p&amp;lt;0.001) and serum cortisone (r=0.22; p=0.001). A binary logistic regression analysis shows that cortisone predicts low-renin phenotype (OR=0.4 [95% CI, 0.21 – 0.78]). The ROC curves show an AUC for serum cortisone was 0.62 (95% CI: 0.54 to 0.69; p = 0.004) and urinary cortisone 0.6 (95% CI: 0.52 to 0.67; p = 0.02) to discriminate subjects with low-renin from controls. Subjects with low serum cortisone showed a higher albuminuria, PAI-1 and lower sodium renal excretion. Urinary free cortisone was also associated to blood pressure and serum potassium (p&amp;lt;0.05). Conclusion: These findings highlight the concept that the low-renin phenotype is dictated not only by serum aldosterone levels but also by low cortisone, suggesting it should be considered in endocrine arterial hypertension screening, complementary in the diagnosis of primary aldosteronism since it could generate false positives in the calculation of the aldosterone to renin ratio. Moreover, our study suggests that low cortisone levels could be associated with future occurrence of vascular and kidney damage. Presentation: Thursday, June 15, 2023

Abstract 108: Rejuvenation Potential Of Extracellular Vesicles From Renal Distal Tubular Cells - A Promising Strategy To Prevent Aging-associated Hypertension And Renal Function Impairment

Ageing is characterized by progressive multi-organ functional decline and disrupted homeostasis adaptation. Hypertension and kidney damage become increasingly prevalent as individuals age. Given its high metabolic activity and constant exposure to reactive oxygen species, the kidney is particularly susceptible to age-related deterioration. In our study, aged mice exhibited a notable decline in glomerular filtration rate (GFR) and urinary excretion of sodium, potassium, and calcium, alongside elevated urinary creatinine levels, indicating impaired renal function associated with ageing. Histologically, aged kidneys showed glomerular collapse, thickening of the glomerular basement membrane, and increased glomerular sclerosis. Cellular senescence plays a critical role in renal ageing. Senescent cells display an array of changes in gene and protein expression and thus also altered the contents packaged into extracellular vesicles (EVs), secreted into the extracellular milieu. The protein and RNA composition of EVs varied depending on the age and pathological status of the originating parent cells. Our data showed an increased expression of EV biogenesis protein HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in aged DCT cells (aDCTs). Consistently, with an increase in EV secretion in aDCTs. Administration of young DCT (yDCT)-derived EVs into aged kidneys resulted in a significant improvement of GFR and urinary ion excretion, accompanied by a reduction in age-associated elevation of systolic blood pressure (SBP). Conversely, when administering aDCT-derived EVs to young mice, we saw a significant decrease in GFR and an increase in SBP, indicating a detrimental effect of aDCT-EVs. Proteomic analysis revealed distinct protein expression profiles between yDCT-EVs and aDCT-EVs. These differentially expressed proteins are highly enriched in ageing regulatory pathways, underscoring the crucial role of DCT-EVs in kidney rejuvenation. Intriguingly, we identified a subset of proteins exclusively present in either yDCT-EVs or aDCT-EVs. Our future research will focus on identifying the key components of DCT-EVs responsible for driving kidney rejuvenation.

Reducing the Sodium Intake of Patients With Chronic Kidney Disease Through Education and Estimating Salt Excretion: A Propensity Score Matching Analysis.

Japanese people traditionally consume high quantities of salt. This study aimed to investigate the effects of educating patients with chronic kidney disease (CKD) on simple methods for reducing their daily dietary salt intake. This single-center, retrospective observational study included 115 outpatients with CKD at Kawashima Hospital (Tokushima, Japan). One physicianroutinely recommended that patients should reduce their salt intake and provided tips for salt restriction. The physician estimated the patients' daily salt intake using spot urine samples at each medical examination (education group; n = 61). The other physicians' outpatients only received dietary guidance on recommended salt intake (control group; n = 54). The estimated 24-hour urinary sodium excretion (24hUNaV) and 24-hour potassium excretion (24hUKV) were calculated using Tanaka's equation. Estimated 24hUNaV was positively correlated with body mass index (BMI), estimated 24hUKV, and urinary Na/K ratio. The patients in the education group were younger and had a lower BMI, higher estimated glomerular filtration rate, and lower systolic blood pressure (SBP). Using 38 pairs of patients obtained by propensity score matching with these variables, estimated 24hUNaV, estimated 24hUKV, and diastolic blood pressure (DBP) after one year were significantly reduced in the education group. A simple salt reduction education may reduce salt intake in outpatients with CKD.

Dietary anions control potassium excretion: it is more than a poorly absorbable anion effect.

The urinary potassium (K+) excretion machinery is upregulated with increasing dietary K+, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K+ secretion through a transepithelial voltage effect. Here, we tested if they also influence the K+ secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO3 diets. The K+ secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K+-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO3 diet increased urinary K+ excretion and the transtubular K+ gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K+ (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO3 diet also uniquely increased the large-conductance Ca2+-activated K+ (BK) channel β4-subunit, stabilizing BKα on the apical membrane, the Cl-/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K+ excretion with the high-KHCO3 diet. In summary, [Formula: see text] stimulates K+ excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K+ wasting and hypokalemia in alkalosis.NEW & NOTEWORTHY Dietary anions profoundly impact K+ homeostasis. Here, we found that a K+-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K+ excretory machinery, epithelial Na+ channels, and renal outer medullary K+ channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO3 secretion pathway. These findings reveal new K+ balance mechanisms that drive adaption to alkaline and K+-rich foods, which should guide new treatment strategies for K+ disorders.

Assessment of 24 h Sodium and Potassium Urinary Excretion in Normotensive and Hypertensive Dominican Adults.

Higher salt (sodium) intake has been associated with higher blood pressure (BP). The degree of association may be influenced by factors such as age, origin, and dietary components. This study aimed to evaluate the 24 h urinary sodium (Na) and potassium (K) excretion in normotensive and hypertensive Dominican adults and estimate their salt intake. 163 volunteers (18-80 years old) participated in a cross-sectional study. The 24 h Na and K urinary excretion were measured using an ion-selective electrode technique. Na and K urinary excretion (99.4 ± 46.5 and 35.0 ± 17.5 mmol/24 h) did not correlate with BP, except in the normotensive group, in which K correlated with SBP (0.249, p = 0.019). Na and K excretion were similar in normotensive and hypertensive subjects. When considering two age groups (18-45, 46-80 years), the Na-to-K molar ratio (3.1 ± 1.3) was higher in younger subjects (p = 0.040). Na-to-K ratio was associated with DBP in the total group (r = 0.153, p = 0.052), in the hypertensive group (r = 0.395, p < 0.001), and in the older group with SBP (0.350, p = 0.002) and DBP (0.373, p < 0.001). In the older group, Na-to-K ratio and DBP correlated after controlling for subjects with hypertension controlled by treatment (r = 0.236, p = 0.041). The Na-to-K ratio correlated, when salt intake was over 5 g/day (52.2%), with SBP (rho = 0.219, p = 0.044) and DBP (rho = 0.259, p = 0.017). Determinants of BP in the total sample were age (SBP, beta: 0.6 ± 0.1, p < 0.001; DBP, beta: 0.2 ± 0.1, p < 0.002), sex (SBP, beta: 11.2 ± 3.5, p = 0.001), body mass index (BMI) (SBP, beta: 1.0 ± 0.3, p < 0.001; DBP, beta: 0.4 ± 0.2, p = 0.01), and Na-to-K ratio (SBP, beta: 3.0 ± 1.1, p = 0.008; DBP, beta: -12.3 ± 4.0, p = 0.002). Sex and BMI were determinants in the younger group. Na-to-K molar ratio was determinant in the older group (SBP, beta: 6.7 ± 2.4, p = 0.005; DBP, beta: 3.8 ± 1.1, p < 0.001). The mean Na and salt intakes (2.3 and 5.8 g/day) were slightly higher and the K intake lower (1.4 g/day) than WHO recommendations.

Awareness and Use of Low-Sodium Salt Substitutes and Its Impact on 24-h Urinary Sodium and Potassium Excretion in China-A Cross-Sectional Study.

The use of low-sodium salt substitute (LSSS) has the potential to reduce sodium and increase potassium intake. LSSS has been available in the Chinese market for years. However, its real-world use and impact on sodium/potassium intake is unclear. Baseline data of 4000 adult individuals who participated in three similarly designed randomized controlled trials were pooled together for this analysis. Self-reported awareness and use of LSSS were collected using a standardized questionnaire, and the participants' 24-h urinary sodium and potassium excretion was used to estimate their dietary intake. Mixed-effects models were developed to assess the relationship between LSSS and 24-h urinary sodium and potassium excretion. 32.0% of the participants reported awareness of LSSS and 11.7% reported its current use. After adjusting for location, sex, age, and education, compared with the group of participants unaware of LSSS, participants who were aware of but not using LSSS and those who were using LSSS had a lower 24-h urinary sodium excretion by -356.1 (95% CI: -503.9, -205.9) mg/d and -490.6 (95% CI: -679.2, -293.7) mg/d, respectively (p < 0.001). No significant difference was found for 24-h urinary potassium excretion or sodium-to-potassium ratio among the three groups (p > 0.05). In conclusion, the findings of low usage of LSSS and the reduced urinary sodium excretion associated with the awareness and use of LSSS provide further support for the prometon of LSSS as a key salt reduction strategy in China.

Low Potassium Intake: A Common Risk Factor for Nephrolithiasis in Patients with High Blood Pressure.

Hypertension (Htn) is a crucial cause of cardio-vascular and chronic kidney disease. Moreover, it is an independent risk factor for nephrolithiasis (NL). A diet rich in vegetables and fruits is indicated for both Htn and NL prevention, and the 24-h urinary potassium excretion can be used as a warning light for adherence. The aim of this study is to demonstrate the association between urinary potassium excretion and recurrent nephrolithiasis among patients affected by Htn. We have analyzed medical records of 119 patients affected by Htn and NL (SF-Hs) referring to Bone and Mineral Metabolism laboratory and 119 patients affected by Htn but without NL (nSF-Hs) referring to Hypertension and Organ Damage Hypertension related laboratory, both in Federico II University of Naples. The potassium 24-h urinary levels in SF-Hs were significantly lower compared to nSF-Hs. This difference was confirmed by the multivariable linear regression analysis in the unadjusted model and adjusted model for age, gender, metabolic syndrome, and body mass index. In conclusion, a higher potassium urinary excretion in 24-h is a protective factor against NL in patients affected by Htn and dietary interventions can be considered for kidney protection.

#4412 URINARY SODIUM-TO-POTASSIUM RATIO DOES NOT ACCURATELY REFLECT DIETARY SODIUM-TO-POTASSIUM RATIO

Abstract Background and Aims Low sodium intake is associated with a lower blood pressure and less proteinuria, which are important therapeutic targets in chronic kidney disease. In contrast, a low potassium intake has been associated with higher blood pressure and a higher incidence of chronic kidney disease and cardiovascular events. Counselling of patients regarding their sodium and potassium intake requires accurate estimation of their intake, but 24-hour urinary sodium and potassium excretion can deviate substantially from actual intake. Urinary sodium-to-potassium (Na/K) ratio is a promising alternative as it is less affected by incomplete urine collections and additionally captures both the effect of sodium and potassium. Our study aimed to assess whether the Na/K ratio in 24-hour urine reflects dietary intake more accurately than separate measurement of sodium or potassium in 24-hour urine. Method We performed a post-hoc analysis on data from the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with a known sodium and potassium content and collected 24-hour urine samples for 105 or 205 days. We calculated the log fold difference between dietary intake and urinary excretion of sodium, potassium and Na/K ratio. A mixed-effects model with a random intercept per subject was used to compare these estimates of accuracy. Subsequently, we performed a subgroup analysis per salt intake level (i.e. 6, 9 or 12 grams per day) and assessed the effect of increasing the number of 24-hour urine collections. Results Overall, the urinary Na/K ratio underestimated dietary Na/K ratio with a median difference of -0.21 (IQR -0.47 to 0.09). Estimation of dietary Na/K ratio intake using the urinary Na/K ratio was significantly less accurate compared to using urinary sodium or potassium measurement for estimation of sodium or potassium intake (Figure 1A). Only during a salt intake of 6 grams per day, the urinary Na/K ratio did not perform significantly worse than sodium measurements. Although increasing the number of 24-hour urine measurements to three or seven improved the accuracy of the urinary Na/K ratio, it remained inferior to separate assessment of urinary sodium and potassium excretion (Figure 1B). Conclusion The 24-hour urinary Na/K ratio is less accurate than 24-hour urinary sodium or potassium excretion for estimation of dietary intake in a controlled setting in healthy volunteers.

#3840 THE SYSTEMIC AND RENAL HAEMODYNAMIC EFFECTS OF APELIN IN HEALTH AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic kidney disease (CKD) is a leading cause of global morbidity and mortality and is independently associated with cardiovascular disease. Indeed, patients with CKD are more likely to die of cardiovascular disease than they are to progress to kidney failure. Despite current standard of care, outcomes remain poor and newer therapies are needed. Apelin, an endothelium-dependent vasodilator and potent inotrope, is a potential novel treatment for CKD. There are no clinical studies of the renal actions of apelin, but pre-clinical data show that it regulates glomerular haemodynamics and promotes aquaresis. We investigated the cardiovascular and renal actions of apelin in healthy volunteers and in patients with CKD. Method Patients with stable, non-diabetic CKD and age- and sex-matched healthy volunteers were recruited to a prospective, randomised, double-blind and placebo-controlled study. Subjects received either pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or placebo on two separate visits. Cardiovascular assessments included blood pressure, impedance cardiography and pulse wave velocity; iohexol and para-aminohippurate clearance were used to assess glomerular filtration rate (GFR) and renal blood flow, respectively. Tubular function was examined via urinary sodium, potassium and free water excretion. Results Twelve patients with CKD and 12 healthy volunteers were recruited and completed both phases of the study protocol. Baseline characteristics are shown in Table 1. Whilst infusion of 1 nmol/min [Pyr1]apelin-13 did not affect systemic haemodynamics, 30 nmol/min [Pyr1]apelin-13 led to significant changes. Compared to placebo, mean arterial pressure fell by 3 mmHg and 4 mmHg in health and CKD, respectively (p&amp;lt;0.05 for both groups), and systemic vascular resistance index fell by 309 dynes*s*cm−5 m2 and 407 dynes*s*cm−5 m2, respectively (p&amp;lt;0.01 for both groups). Cardiac index increased by 0.3 L/min/m2 and 0.2 L/min/m2, respectively (p&amp;lt;0.05 for both groups compared to placebo). In contrast, both 1 nmol/min and 30 nmol/min [Pyr1]apelin-13 had similar effects on renal haemodynamics. Effective renal blood flow increased by ∼15% in health and CKD (p&amp;lt;0.01 compared to placebo for both groups). GFR fell by ∼4 mL/min compared to placebo in patients with CKD (p&amp;lt;0.01) but we observed no change in healthy volunteers. As a result of these changes in effective renal blood flow and GFR, filtration fraction fell by ∼3% in CKD, reflected by a fall in proteinuria of ∼25% (p&amp;lt;0.001 compared to placebo for both). Both low and high doses of [Pyr1]apelin-13 promoted natriuresis and free water clearance in health and CKD. In comparison to placebo, sodium excretion increased by ∼30% and free water clearance by ∼15% in both groups (p&amp;lt;0.05 for all comparisons). Overall, the effects of apelin were prolonged in CKD. Conclusion Apelin offers systemic and renal haemodynamic benefits to patients with CKD. If these effects were maintained longer-term they would translate to improved cardiovascular and renal outcomes in this at-risk patient group. Clinical trials of long-acting, oral apelin analogues are now justified in CKD and other conditions with impaired salt and water balance.