Urinary Potassium Excretion Research Articles

24-hour urinary potassium excretion is negatively associated with self-reported sleep quality in the general population, independently of sleep-disordered breathing.

To investigate the association of 24-hour urinary potassium excretion with self-reported sleep quality in the general population. In this cross-sectional study, a population of patients aged 18 years or older was randomly selected from Xinjiang, China in 2019, 24-hour urine samples collected, and Pittsburgh Sleep Quality Index (PSQI) questionnaires assessed. Participants were divided into 2 groups (upper and lower median of 24-hour urinary potassium excretion). Poor sleep quality was defined as PSQI global score ≥ 6. Associations between 24-hour urinary potassium excretion and [24.8 mmol/L] sleep quality were assessed by multiple logistic regression analysis in total participants and those stratified by sex. In total, 24-hour urine samples were collected from 1,147 participants, of whom data for those with complete urine samples and PSQI data were analyzed (n = 727; mean age = 48.7 years; percentage of women = 62%). Compared with the upper median group for 24-hour urinary potassium excretion, the lower median group showed a significantly higher PSQI global score (6 vs 5, P = .011), and prevalence of poor sleep quality (51.7% vs 42.2%, P = .011). In a fully-adjusted model of multivariate logistic regression, the lower median group showed 1.50-fold increased odds for presence of poor sleep quality (95% confidence interval: 1.01-2.24, P = .045). Sex-specific analyses translated these results to women, but not to men. These results suggest that low potassium intake, indicated by lower potassium excretion, is associated with poor sleep quality in the general population, especially among women. Therefore, additional research is necessary to clarify the effect of increasing potassium intake to improve sleep quality. Li M, Heizhati M, Wang L, etal. 24-hour urinary potassium excretion is negatively associated with self-reported sleep quality in the general population, independently of sleep-disordered breathing. J Clin Sleep Med. 2022;18(11):2589-2596.

Blood pressure interactions with the DASH dietary pattern, sodium, and potassium: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP)

ABSTRACTBackgroundAdherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear.ObjectivesAmong free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved.MethodsWe used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP). Multiple linear regression and cross-tabulation analyses were used to investigate the DASH-BP relation and its modulation by sodium and potassium. Potential pathways associated with DASH adherence, sodium and potassium excretion, and BP were identified using mediation analyses and metabolic reaction networks.ResultsAdherence to the DASH diet was associated with urinary potassium excretion (correlation coefficient, r = 0.42; P < 0.0001). In multivariable regression analyses, a 5-point higher DASH score (range, 7 to 35) was associated with a lower systolic BP by 1.35 mmHg (95% CI, −1.95 to −0.80 mmHg; P = 1.2 × 10−5); control of the model for potassium but not sodium attenuated the DASH-BP relation. Two common metabolites (hippurate and citrate) mediated the potassium-BP and DASH-BP relationships, while 5 metabolites (succinate, alanine, S-methyl cysteine sulfoxide, 4-hydroxyhippurate, and phenylacetylglutamine) were found to be specific to the DASH-BP relation.ConclusionsGreater adherence to the DASH diet is associated with lower BP and higher potassium intake across levels of sodium intake. The DASH diet recommends greater intake of fruits, vegetables, and other potassium-rich foods that may replace sodium-rich processed foods and thereby influence BP through overlapping metabolic pathways. Possible DASH-specific pathways are speculated but confirmation requires further study. INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov.

Jeremiah Stamler, MD (1919-2022).

Jeremiah Stamler, MD (1919-2022).

Study on the Correlation between Urinary Sodium and Potassium Excretion and Blood Pressure in Adult Hypertensive Inpatients of Different Sexes

Objective This study aims to understand the difference in the influence of urinary sodium and potassium excretion on blood pressure in patients of different sexes with hypertension by analyzing the relationship between urinary sodium and potassium excretion and blood pressure. Methods In this cross-sectional study, 606 hospitalized patients with essential hypertension were recruited from 16 hospitals in the Shanxi Province between June 2018 and December 2019. These patients were grouped by sex, with 368 males and 238 females. Basic information and relevant serum biochemical indexes of patients in the two groups were recorded. The 24-hour urinary sodium and potassium excretion were measured, and 24-hour ambulatory blood pressure monitoring was performed simultaneously. This was done to analyze and compare the relationship between urinary sodium and urinary potassium excretion and blood pressure in adult hospitalized patients of different sexes with hypertension. Results The 24-hour urinary sodium excretion in male patients with hypertension was significantly higher than that in female patients (P < 0.001). There was no significant difference in 24-hour urinary potassium excretion between male patients with hypertension and female patients. Spearman correlation analysis showed that 24-hour urinary sodium excretion was positively correlated with 24-hour SBP and nSBP in male patients (P < 0.05), while 24-hour urinary potassium excretion was negatively correlated with 24-hour SBP and nSBP in male patients (P < 0.05). The 24-hour urinary sodium in female patients was significantly positively correlated with 24-hour SBP, 24-hour DBP, SBP, dDBP, nSBP, and nDBP (P < 0.01). The 24-hour urinary potassium was significantly negatively correlated with nSBP (P < 0.05). Multiple stepwise linear regression showed that 24-hour urinary sodium excretion was still significantly positively correlated with 24-hour SBP and nSBP in male patients with hypertension after adjusting for various confounding factors. Conclusion High urinary sodium and low urinary potassium excretion are closely related to elevated blood pressure in adult patients with hypertension, and there are sex differences.

Body, metabolic and renal changes following cross-sex estrogen/progestogen therapy in a rodent model simulating its use by transwomen.

The use of sex steroids by trans people has been of paramount importance regarding body changes during gender transition. The objective of this study was to assess the effects of an injectable steroid combination frequently used by transwomen, namely estradiol enanthate with dihydroxyprogesterone acetophenide (E2EN/DHPA), on blood pressure and metabolic outcomes using an animal model. Two-month-old male Wistar rats were orchiectomized or sham-operated and divided into groups: (1) Sham treated with sesame oil vehicle (SG), (2) sham treated with E2EN/DHPA (SP), (3) orchiectomized rats treated with vehicle (OG), and (4) orchiectomized rats treated with E2EN/DHPA (OP), with all groups treated every 10days for 5 months. We evaluated systolic blood pressure (SBP), body weight (BW), abdominal circumference, nasoanal length (NAL), food and water intake (FI, WI), lipid profile (triglycerides, LDL, and HDL), serum C-reactive protein (CRP), plasma concentrations of urea (URpl) and creatinine (CRpl), 24h urinary volume (V24h), sodium and potassium excretion (UNa+, UK+), and proteinuria. E2EN/DHPA administration reduced BW (SP 324.5 ± 31.1; OP 291.7 ± 41.3g) and NAL (SP 24.5 ± 0.4; OP 24.6 ± 1.0cm), without changing blood pressure, but increased URpl concentration (SP 55.0 ± 4.8; OP 42.5 ± 8.8mg/dL) and CRpl (SP 0.47 ± 0.05; OP 0.46 ± 0.04mg/dL), sodium (SP 3.1 ± 0.8; OP 3.3 ± 0.4µEq/min/kg), potassium (SP 0.91 ± 0.22; OP 0.94 ± 0.22µEq/min/kg) excretions and urinary volume (SP 15.5 ± 2.1; OP 16.4 ± 2.9mL/24h). Cross-sex hormone therapy with E2EN/DHPA significantly modified body characteristics in male rats, producing a feminizing change without altering blood pressure or generating harmful metabolic parameters, but larger translational studies are still needed.

Prediction Tool to Estimate Potassium Diet in Chronic Kidney Disease Patients Developed Using a Machine Learning Tool: The UniverSel Study.

There is a need for a reliable and validated method to estimate dietary potassium intake in chronic kidney disease (CKD) patients to improve prevention of cardiovascular complications. This study aimed to develop a clinical tool to estimate potassium intake using 24-h urinary potassium excretion as a surrogate of dietary potassium intake in this high-risk population. Data of 375 adult CKD-patients routinely collecting their 24-h urine were included to develop a prediction tool to estimate potassium diet. The prediction tool was built from a random sample of 80% of patients and validated on the remaining 20%. The accuracy of the prediction tool to classify potassium diet in the three classes of potassium excretion was 74%. Surprisingly, the variables related to potassium consumption were more related to clinical characteristics and renal pathology than to the potassium content of the ingested food. Artificial intelligence allowed to develop an easy-to-use tool for estimating patients’ diets in clinical practice. After external validation, this tool could be extended to all CKD-patients for a better clinical and therapeutic management for the prevention of cardiovascular complications.

CIRCADIAN BLOOD PRESSURE PROFILE IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION

Objective: Disturbed circadian blood pressure (BP) profile is a risk factor for cardiovascular complications in adults. The study aimed to evaluate factors affecting circadian BP profile and its association with hypertension-mediated organ damage (HMOD) in pediatric patients with primary hypertension (PH). Design and method: The study included 112 children (79 boys, 33 girls, 14.7 ± 2.7 years) with untreated PH. Circadian BP profile was assessed by 24-hour ABPM. Disturbed circadian BP profile (non-dipping) was defined as a nocturnal drop in systolic or diastolic BP (SBP, DBP) &lt; 10%. A nocturnal drop in SBP or DBP &gt; 20% was defined as extreme dipping. Patients were evaluated for central BP, HMOD (left ventricular mass index - LVMI, aortic pulse wave velocity, augmentation index (AIx75HR), intima-media thickness, albuminuria), and clinical and biochemical parameters, including sodium-potassium balance. Results: In the study group, the mean nocturnal drop in SBP was 10.9 ± 5.9 [%] and in DBP - 16.2 ± 8.5 [%]. Non-dipping was found in 50 (44.6%) children and extreme-dipping in 29 (25.9%) patients. The nocturnal drop in SBP correlated negatively with Z-scores of body weight (r = -0.191, p = 0.043) and BMI (r = -0.242, p = 0.010) and with LVMI [g/m2.7] (r = -0.395, p = 0.006). The nocturnal drop in SBP and DBP correlated positively with urinary potassium excretion [mmol/kg/24 h] (r = 0.656, p = 0.001 and r = 0.540, p = 0.011, respectively). Patients with disturbed circadian blood pressure profile were characterized by higher LVMI (44.5 ± 12.5 vs. 36.8 ± 8.8 [g/m2.7]) and albuminuria (median: 10.8, IQR: 5.3–53.3 vs. median: 8.1, IQR: 5.5–16.4 [mg/24 h], p = 0.043) and lower urinary potassium excretion (0.6 ± 0.2 vs. 1.1 ± 0.3 [mmol/kg/24 h]). Extreme-dipping patients had a higher AIx75HR than the other patients (median: + 3.3, IQR: -6.3- + 17.7 vs. -4.6, IQR: -17.3- + 4.0 [%], p = 0.048). Conclusions: 1. Disturbed circadian BP profile is common in children with PH and should not be considered a marker of secondary hypertension. 2. Disturbed circadian BP profile may be associated with higher body weight and lower dietary potassium intake. 3. Pediatric patients with PH and disturbed BP profile are at risk for HMOD: left ventricular hypertrophy and microalbuminuria. 4. Extreme-dipping may be associated with increased arterial stiffness in children with PH.

MO093: Dietary Sodium Restriction Reduces Nocturnal Blood Pressure in Treatment Resistant Hypertensive Patients

Abstract BACKGROUND AND AIMS High blood pressure (BP) is an essential contributor to the risk of cardiovascular disease (CVD) and death. Hence, diagnosing and treating patients with high BP is paramount if the number of cardiovascular related death should be reduced. High nocturnal BP and blunting of normal nocturnal BP decrease have stronger correlation to the risk of CVD than high day time BP. Lowering nocturnal BP is assumed to reduce the risk of CVD. Patients with treatment resistant hypertension (TRH) represent a subgroup of hypertensive patients characterized by lack of BP control despite antihypertensive treatment. These patients are at particular risk of CVD and target organ damage. Patients with TRH are more likely to experience BP increase as a response to sodium loading than other individuals. Lifestyle modification is an important treatment angle in hypertensive patients. It is, in particular, central to reduce sodium intake, as high sodium intake increases the risk of TRH. Thus, in this study we aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH. Moreover, we aimed to analyse the effect of this attempted restriction on nocturnal BP and 24 h BP, on plasma levels of BNP and nitric oxide, and on body water content. METHOD Patients with TRH from 20 to 70 years with normal renal function were invited for participation in this cross-over interventional study. Patients were screened with 24 h ambulatory BP monitoring initiated after observed intake of usual antihypertensive medication, and they were included if 24 h systolic BP/diastolic BP ≥ 130/80 mmHg. Study participation included two periods of 14 days; a standard period with usual diet and an interventional period with instructed dietary sodium restriction and handed-out sodium-reduced bread. For both periods, all antihypertensive medication was dosed and handed out and ingested in the morning. At the end of each period, patients were examined with 24 h BP monitoring, 24 h urine collection (sodium excretion), blood samples (nitric oxide and BNP) and bioimpedance measurement (body water content). RESULTS Baseline characteristics of the fifteen included patients are shown in Table 1. Eleven of the patients were male. Patients had been treated for hypertension for a mean of 12.5 (7) years and excreted a mean of 11.2 grams of salt at baseline [192 (86) mmol sodium]. All patients but one reduced sodium excretion at follow up. Table 2 shows the effect of sodium restriction on BP, nitric oxide, BNP and body water content. Sodium excretion was reduced to 91 mmol/24 h, which equals 5.3 g of salt. BP (24 h, day and nocturnal) decreased significantly as well as body water content and plasma levels of BNP. These changes were, however, not correlated. Plasma levels of nitric oxide increased, but it was not related to the changes in BP. Nocturnal fraction of 24 h sodium excretion increased after sodium restriction; however, this was not correlated to changes in nocturnal BP. Renal function and urinary potassium excretion both remained unchanged. Four patients experienced side effects; three reported newly onset dizziness at follow-up; two of them had 24 h BP reduction &amp;gt; 10 mmHg systolic. One patient had increased creatinine and potassium at follow-up. CONCLUSION In a population of 15 treatment resistant hypertensive patients, we demonstrated that self-performed dietary sodium restriction could be implemented. Urinary sodium excretion was reduced significantly to 5.3 g/24 h. Nocturnal BP was reduced significantly; dipping status was, however, unchanged. Increased plasma levels of nitric oxide may be evidence of improved endothelial function. Hence, by the local vasodilating effect, NO may be one of the involved mechanisms in BP decrease following a sodium restriction. Reduced extracellular water content and BNP may be other explainable effects of BP reduction after inducing sodium restriction.

Angiotensin Ii‐induced Hypertension and Glomerular and Tubulointerstitial Injury in Mutant Mice With Kidney Proximal Tubule‐selective Deletion of Mitochondrial Nad+‐dependent Deacetylase Sirtuin 3: Focus on Sex Differences

Sirtuin 3 (SIRT3) is a major mitochondrial NAD‐dependent Deacetylase closely involved in energy production, cell metabolism, oxidative stress responses, and mitochondrial homeostasis during hypertension and kidney diseases. However, it remains unknown whether deletion of SIRT3 in the proximal tubules alters the hypertensive and kidney glomerular and tubulointerstitial fibrotic responses to angiotensin II (Ang II) in sex‐dependent manners. In the present study, adult male and female wild‐type (WT) and mutant mice with proximal tubule‐specific deletion of SIRT3, PT‐Sirt3‐/‐, were infused without (time controls) or with a slow pressor dose of Ang II via an osmotic minipump (0.5 mg/kg/day, i.p.), supplemented with a 2% NaCI diet or losartan, 20 mg/kg/day, for 2 weeks. Systolic (SBP), diastolic (DBP), and mean arterial blood (MAP) pressure were determined using the tail‐cuff method, whereas 24 hr. urinary sodium and potassium excretion were determined using a metabolic cage. Serum and urine creatinine were measured using colorimetric assays, whereas glomerular and tubulointerstitial injury was evaluated by Masson’s Trichrome staining. Basal SBP, DBP, and MAP were significantly lower in PT‐Sirt3‐/‐ mice than WT (WT‐SBP: 112 ± 2 vs. PT‐Sirt3‐/‐‐SBP: 93 ± 2 mmHg, P&lt;0,01). The magnitude of Ang II‐induced hypertension was similar between WT and PT‐Sirt3‐/‐ mice with or without losartan treatment. After the establishment of hypertension, both WT and PT‐Sirt3‐/‐ animals significantly increased urine creatinine levels in both males and females (P&lt;0.05). However, male PT‐Sirt3‐/‐ mice had higher urine creatinine excretion than male WT (WT‐Ang II: 734 ± 59 vs PT‐Sirt3‐/‐‐Ang II: 1155 ± 92, µg/mL, P&lt;0.05), but this sex difference was absent in female WT and PT‐Sirt3‐/‐ mice. In general, females had a lower urinary creatinine excretion (UCr) than males. Losartan treatment decreased urinary creatinine excretion in all groups (P&lt;0.05). Similar responses were observed with plasma creatinine levels (SCr), which were higher in PT‐Sirt3‐/‐mice than in WT mice (P&lt;0.05), but without significant sex differences in response to Ang II infusion or losartan treatment. Losartan significantly increased 24 hr urinary potassium and chloride excretion in Ang II‐infused male and female PT‐Sirt3‐/‐ mice (P&lt;0.01). Finally, Ang II‐infused PT‐Sirt3‐/‐ mice showed significant glomerular and renal cortical tubulointerstitial fibrotic responses, compared with WT (P&lt;0.05), without sex differences. Interestingly, losartan treatment did not show decreased fibrotic responses, instead, showed a tendency to higher collagen deposition than in hypertensive PT‐Sirt3‐/‐ mice. In summary and conclusion, male and female PT‐Sirt3‐/‐ mice have lower basal blood pressure, and Ang II‐induced hypertension and renal fibrotic responses are similar in male and female PT‐Sirt3‐/‐ mice without significant sex differences. Our results suggest that AT1a receptors and SIRT3 play important roles in basal blood pressure homeostasis and Ang II‐induced hypertension and glomerular and tubulointerstitial injury in both male and female mice.

Urinary Potassium Excretion Inversely Correlates with Diastolic Blood Pressure Variability in Healthy Normotensive Adults

High blood pressure (BP) is a common risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. Dietary intake is an important contributor to BP. Increased dietary sodium intake has been shown to increase BP, while evidence suggests dietary potassium decreases BP. BP variability (BPV) refers to spontaneous fluctuations in BP that if exaggerated, are considered a risk factor for CVD. Limited work in this area suggests a high sodium diet may relate to increased BPV while potassium may decrease BPV. The purpose of our study was to investigate whether dietary intake of sodium and potassium relates to BPV in healthy, normotensive subjects. We hypothesized that individuals with a higher sodium intake, as well as increased sodium to potassium excretion ratio, would exhibit a higher BPV while those with increased potassium intake would have a lower BPV. Healthy men and women between the ages of 18 and 45 were recruited to participate. Habitual sodium and potassium intake was quantified with 24‐hour urine samples. During this same time period, subjects wore an ambulatory BP monitor for 24 hours with measures taken every 20 minutes during the day and every 30 minutes at night. These data were used to determine short term BPV. BPV was quantified by calculating the average real variability (ARV) index. Pearson bivariate correlations were run to assess the relation between sodium, potassium, and the sodium to potassium excretion ratio and the ARV of both systolic and diastolic BP. Additionally, partial correlations were run to control for the effects of age and sex. Fifty‐six (20M/36W) subjects (27±1 year; BMI 23±0.4; BP 114±1/67±1 mmHg) participated. Twenty‐four‐hour urinary potassium excretion was inversely associated with the ARV of diastolic BP (r=‐0.33, p=0.02). When controlling for age and sex this relation remained (r=‐0.31, p=0.03). However, neither 24‐hour urinary sodium excretion or the sodium to potassium excretion ratio was associated with the ARV of systolic (r=‐0.25, p=0.07; r=‐0.10, p=0.48, respectively) or diastolic BP (r=‐0.12, p=0.41; r=0.11, p=0.43, respectively). In summary, in this cohort of healthy normotensive adults, a higher potassium intake was associated with a lower diastolic BPV; however, there was no relation with sodium or the sodium to potassium excretion ratio. More research is needed to better understand the effects of both sodium and the ratio of sodium to potassium intake on BPV in healthy normotensive men and women.

Role of Dipeptidyl Peptidase 4 and Effects of a Western Diet in Renal Sodium Transport and Tubular Injury

The protein dipeptidyl peptidase 4 (DPP4) is a target in the management of Type 2 diabetes mellitus (T2DM) and inhibition decreases albuminuria in humans with high cardiovascular risk such as subjects with T2DM, obesity/insulin resistance and hypertension. Our laboratory and others have shown that inhibition or genetic deletion of DPP4 has nephroprotective effects not only in rodent models of DM/insulin resistance but also obesity and hypertension. In addition, all three conditions with high cardiovascular risk are characterized by sodium retention. Recent data shows that DPP4 may affect sodium transport within the kidney via binding to sodium/hydrogen exchanger 3 (NHE3) and translocating to the villi in the brush border of the tubules. We have observed increased tubular damage and sodium uptake in a high fat/high sugar diet (Western diet) model of obesity in the setting of increased DPP4 activity. Therefore, we hypothesized that reduction/suppression of DPP4 expression/signaling and/or activity may lead to decreased sodium retention in the kidney in the obese mice.MethodsProximal tubule specific DPP4fl/fl;SGLT2Cre+ (PT DPP4KO) and DPP4fl/fl;SGLT2Cre‐ (PT DPP4WT) mice were fed a WD and control chow (CD) till sacrifice (18 to 27 mths). 24 hour urine collection and measurement of sodium excretion was done in these mice while on the diets. Gene and protein expression of transporters (sodium and water) was quantitated. Whole body DPP4‐/‐ (DPP4KO) and DPP4+/+ (DPP4WT) were on control chow diet and placed in metabolic cages for sodium balance studies. On days 3 and 4, mice were given 1% NaCl in drinking water. Daily mice weight, food and water consumption and urinary excretion of sodium and potassium and creatinine were measured.ResultsThe PT DPP4WT mice showed a much reduced 24 hour excretion of sodium compared to the PT DPP4KO mice (p&lt;0.05) which was consistent with data from DPP4WT and DPP4KO mice on WD (unpublished) as well as data from DPP4 inhibitor treated mice (Nistala et al, Endocrinology 2014 Jun;155(6):2266‐76). Urinary sodium excretion was increased in both DPP4WT and DPP4KO mice on 1% NaCl in drinking water but the excretion was significantly increased in DPP4KO mice compared to DPP4WT mice. Excretion of glucose and other electrolytes reached a peak on the 3rd day and tapered off slightly on the 4th day. The increased excretion of sodium and water as well as slight reduction in food intake, led to gradual decrease in weight of the animals (~1gm) which was not significant between the WT and KO groups. The gene expression of many sodium and water transporters increased including NHE3, ENaCγ and AQP1/2 in the PT DPP4WT mice, while expression was reduced in the PT DPP4KO mice fed a Western Diet. The protein expression of NHE3 increased in WT mice and was suppressed in KO mice.ConclusionDPP4 expression was increased in PT DPP4WT mice fed a Western diet and reduced in the KO mice and this correlated with increased expression of NHE3 in the WT and reduction in KO mice. In the whole body DPP4KO mice, lack of DPP4 led to greater increase in sodium and water excretion. Taken together, proximal tubule DPP4 may be involved in regulating sodium and water homeostasis in CD and WD‐fed mice. Sodium excretion under conditions of low salt diet will help establish DPP4's role in sodium homeostasis.

Difelikefalin, a peripherally restricted kappa opioid receptor agonist, evokes diuresis through a central kappa opioid receptor pathway

Kappa opioid receptor (KOR) agonists produce a variety of beneficial effects such as nonaddictive analgesia and diuresis, but their translation into the clinic has been hindered by central adverse effects (dysphoria). In clinical studies, difelikefalin, a KOR agonist recently FDA approved for treatment of pruritus in hemodialysis patients, was shown to be devoid of producing adverse CNS effects suggesting that this compound is peripherally restricted. This is of interest from a renal excretory perspective, since it would be predicted that difelikefalin would not produce diuresis, which is a classical centrally mediated response produced by KOR agonists. However, in preliminary studies in rats we have shown that IV administration of difelikefalin markedly increased urine output and decreased urinary sodium and potassium excretion similar to that produced by other KOR agonists. Therefore, we hypothesized that difelikefalin activates a central KOR pathway to cause diuresis. To test this hypothesis, Sprague‐Dawley rats were implanted with bladder, femoral artery, and femoral vein catheters and administered an isotonic saline infusion. To delineate the central and/or peripheral site of action of difelikefalin, renal excretory function was measured in rats pretreated centrally or peripherally with norBNI (KOR antagonist) or vehicle via an intracerebroventricular (ICV) cannula or IV catheter. Following stabilization, conscious rats were administered an IV bolus of difelikefalin (10 µg/kg) and urine output, mean arterial pressure (MAP), and heart rate (HR) were recorded for 90 minutes. The results demonstrated that ICV norBNI pretreatment significantly decreased the diuretic response to IV difelikefalin but had no effect on urinary sodium or potassium concentration (Table 1). In contrast, IV norBNI pretreatment prevented the diuresis to IV difelikefalin and increased urinary sodium/potassium concentration (Table 1). Notably, ICV and IV norBNI pretreatment abolished the difelikefalin‐induced decrease in MAP that was also seen in the vehicle pretreated groups. Together, these findings suggest that difelikefalin produces its diuretic and blood pressure effects through a central KOR pathway, while the sodium/potassium retaining effects of difelikefalin are mediated through peripheral KORs.

Sodium and potassium intakes assessed by 24-h urine among Moroccan University students in Casablanca, Morocco: Cross-sectional study

In Morocco, the high consumption of dietary sodium increases the risk of non-communicable diseases (NCDs) and predisposes to cardiovascular diseases (CVDs) and hypertension. This study aims to assess the dietary sodium and potassium intake in a random sample of Moroccan adult students as a benchmark informing a national strategy for reducing salt intake. This cross-sectional study was conducted with 103 adults aged 18 to 25 years recruited in Casablanca. The 24-hour urinary excretion was used to measure the sodium and potassium. Urine volume and creatinine excretion level were used to validate the completeness of the collected samples. The average urinary sodium excretion was 3.1±0.1g/day, 13.5% consumed less than 5g/day, while 69% consumed more than 5g/day of which 17.5% consumed more than twice the recommendations. For the average urinary potassium excretion was 1.83±0.06g/day, and more than 98% of the students consumed less than the adequate intake. The Na/K ratio is significantly higher than the recommended amounts. The results of this pilot study show that the population studied has a high sodium intake and low potassium intake which does not meet World Health Organization (WHO) recommendations, which requires implementing an action plan to reduce salt intake.

Sodium and potassium intakes and adiposity among Iranian pre-adolescents and adolescents: a cross-sectional study

BackgroundHigh sodium and low potassium intakes are associated with the early development of chronic diseases (e.g., hypertension, obesity). Taking into account the limited data on sodium and potassium intakes by 24-h excretion in urine in pre-adolescents and adolescents, we wished to determine baseline salt intake in Iranian subjects aged 11–18 years.MethodsThis was an observational study involving 374 pre-adolescents and adolescents (154 boys and 220 girls). Sodium and potassium intakes were ascertained by measuring sodium and potassium excretion in urine over 24 h. Creatinine level was used to validate the completeness of the urine collections. The association between sodium and potassium intake and adiposity was determined based on body fat percentage.ResultsThe mean 24-h urine sodium concentration was 3130 ± 2200 mg/day, equal to 7.961 ± 5.596 g/day salt intake. Approximately half of the study participants exceeded the upper limit of Na intake. The mean potassium intake was estimated 1480 ± 1050 mg/day. There was a positive association between urinary sodium excretion and adiposity in crude (OR 1.79; 95% CI: 1.08—2.74) and full adjusted model (OR: 3.15; 95% CI: 2.28–4.63). Also, in subsample analysis, there was a positive correlation between urinary sodium and adiposity in both pre-adolescents (OR: 2.71; 95% CI: 2.29—3.93) and adolescents (OR: 3.55; 95% CI: 2.17—4.74). However, no significant association was found between 24-h urinary potassium and adiposity.ConclusionSodium intake, as estimated by 24-h urinary excretion, was higher than recommended and it was positively associated with adiposity. Also, this study reported low compliance of potassium intake recommendations in 11–18 years’ Iranian pre-adolescents and adolescents. Health promotion interventions are needed in order to broaden public awareness of high sodium intake and potassium inadequacy to reduce chronic diseases.

The association of arterial stiffness with estimated excretion levels of urinary sodium and potassium and their ratio in Chinese adults.

Arterial stiffness is an independent cardiovascular risk factor. However, the association between sodium/potassium intake and arterial stiffness in the Chinese population is unclear. Therefore, we performed a large, community-based cross-sectional study to reach a more definitive conclusion. The study was conducted at the Third Xiangya Hospital in Changsha between August 2017 and September 2019. Urinary sodium, potassium, and creatinine levels were tested from spot urine samples during physical examinations of each recruited participant. The 24-hour estimated urinary sodium excretion (eUNaE) and estimated urinary potassium excretion (eUKE) levels were calculated using the Kawasaki formula (used as a surrogate for intake). The brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) were measured using an automatic waveform analyzer. In 22,557 subjects with an average age of 49.3 ± 10.3 years, the relationships of the ABI and baPWV with the levels of eUNaE, eUKE and the ratio of sodium to potassium (Na/K ratio) were analyzed. A significant negative relationship was found between the eUKE and baPWV levels (β = 2.41, p < 0.01), whereas the Na/K ratio was positively associated with baPWV (β = 2.46, p < 0.01), especially in the overweight and hypertensive populations (both pinteraction = 0.04). The association of eUNaE quartiles with baPWV presented a J-shaped curve after adjusting for confounders. In addition, a positive association was observed between the Na/K ratio and the ABI (β = 0.002, p < 0.01). In this study, high potassium and/or low sodium intake was further confirmed to be related to vascular stiffness in Chinese individuals.

The relation between urinary sodium and potassium excretion and risk of cardiovascular events and mortality in patients with cardiovascular disease.

Most evidence on the relationship between sodium and potassium intake and cardiovascular disease originated from general population studies. This study aimed to evaluate the relation between estimated 24-hour sodium and potassium urinary excretion and the risk of recurrent vascular events and mortality in patients with vascular disease. 7561 patients with vascular disease enrolled in the UCC-SMART cohort (1996-2015) were included. Twenty-four hour sodium and potassium urinary excretion were estimated (Kawasaki formulae) from morning urine samples. Cox proportional hazard models with restricted cubic splines were used to evaluate the relation between estimated urinary salt excretion and major adverse cardiovascular events (MACE; including myocardial infarction, stroke, cardiovascular mortality) and all-cause mortality. After a median follow-up of 7.4 years (interquartile range: 4.1-11.0), the relations between estimated 24-hour sodium urinary excretion and outcomes were J-shaped with nadirs of 4.59 gram/day for recurrent MACE and 4.97 gram/day for all-cause mortality. The relation between sodium-to-potassium excretion ratio and outcomes were also J-shaped with nadirs of 2.71 for recurrent MACE and 2.60 for all-cause mortality. Higher potassium urinary excretion was related to an increased risk of both recurrent MACE (HR 1.25 per gram potassium excretion per day; 95%CI 1.13-1.39) and all cause-mortality (HR 1.13 per gram potassium excretion per day; 95%CI 1.03-1.25). In patients with established vascular disease, lower and higher sodium intake were associated with higher risk of recurrent MACE and all-cause mortality. Higher estimated 24-hour potassium urinary excretion was associated with a higher risk of recurrent MACE and all-cause mortality.

Insufficient Fruit and Vegetable Intake and Low Potassium Intake Aggravate Early Renal Damage in Children: A Longitudinal Study.

Insufficient fruit and vegetable intake (FVI) and low potassium intake are associated with many non-communicable diseases, but the association with early renal damage in children is uncertain. We aimed to identify the associations of early renal damage with insufficient FVI and daily potassium intake in a general pediatric population. We conducted four waves of urine assays based on our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We investigated FVI and other lifestyle status via questionnaire surveys and measured urinary potassium, β2-microglobulin (β2-MG), and microalbumin (MA) excretion to assess daily potassium intake and renal damage among 1914 primary school children. The prevalence of insufficient FVI (<4/d) was 48.6% (95% CI: 46.4%, 50.9%) and the estimated potassium intake at baseline was 1.63 ± 0.48 g/d. Short sleep duration, long screen time, lower estimated potassium intake, higher β2-MG and MA excretion were significantly more frequent in the insufficient FVI group. We generated linear mixed effects models and observed the bivariate associations of urinary β2-MG and MA excretion with insufficient FVI (β = 0.012, 95% CI: 0.005, 0.020; β = 0.717, 95% CI: 0.075, 1.359), and estimated potassium intake (β = −0.042, 95% CI: −0.052, −0.033; β = −1.778, 95% CI: −2.600, −0.956), respectively; after adjusting for age, sex, BMI, SBP, sleep duration, screen time and physical activity. In multivariate models, we observed that urinary β2-MG excretion increased with insufficient FVI (β = 0.011, 95% CI: 0.004, 0.018) and insufficient potassium intake (<1.5 g/d) (β = 0.031, 95% CI: 0.023, 0.038); and urinary MA excretion increased with insufficient FVI (β = 0.658, 95% CI: 0.017, 1.299) and insufficient potassium intake (β = 1.185, 95% CI: 0.492, 1.878). We visualized different quartiles of potassium intake showing different renal damage with insufficient FVI for interpretation and validation of the findings. Insufficient FVI and low potassium intake aggravate early renal damage in children and underscores that healthy lifestyles, especially adequate FVI, should be advocated.

Determinants of hypokalemia following hypertonic sodium bicarbonate infusion.

The hypokalemic response to alkali infusion has been attributed to the resulting extracellular fluid (ECF) expansion, urinary potassium excretion, and internal potassium shifts, but the dominant mechanism remains uncertain. Hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) to unanesthetized dogs with normal acid-base status or one of the four chronic acid-base disorders decreased plasma potassium concentration ([K+]p) at 30 min in all study groups (Δ[K+]p, - 0.16 to - 0.73 mmol/L), which remained essentially unaltered up to 90-min postinfusion. ECF expansion accounted for only a small fraction of the decrease in ECF potassium content, (K+)e. Urinary potassium losses were large in normals and chronic respiratory acid-base disorders, limited in chronic metabolic alkalosis, and minimal in chronic metabolic acidosis, yet, ongoing kaliuresis did not impact the stability of [K+]p. All five groups experienced a reduction in (K+)e at 30-min postinfusion, Δ(K+)e remaining unchanged thereafter. Intracellular fluid (ICF) potassium content, (K+)i, decreased progressively postinfusion in all groups excluding chronic metabolic acidosis, in which a reduction in (K+)e was accompanied by an increase in (K+)i. We demonstrate that hypokalemia following hypertonic NaHCO3 infusion in intact animals with acidemia, alkalemia, or normal acid-base status and intact or depleted potassium stores is critically dependent on mechanisms of internal potassium balance and not ECF volume expansion or kaliuresis. We envision that the acute NaHCO3 infusion elicits immediate ionic shifts between ECF and ICF leading to hypokalemia. Thereafter, maintenance of a relatively stable, although depressed, [K+]e requires that cells release potassium to counterbalance ongoing urinary potassium losses.

Renal function during sevoflurane or total intravenous propofol anaesthesia: a single-centre parallel randomised controlled study

BackgroundThe choice of anaesthetic may influence regulation of renal perfusion and function. We investigated renal function in patients anaesthetised with propofol or sevoflurane before surgery and postoperatively. MethodsPatients with ASA physical status 1–2 planned for spinal surgery were randomised to propofol or sevoflurane anaesthesia. Blood and urine were collected before anaesthesia, during anaesthesia (before surgery), during postoperative care, and the day after surgery. ResultsTwenty-seven patients completed the study protocol (average age, 51 yr; average BMI, 28 kg m−2) and 11 were women. Urine output and sodium excretion were lower during sevoflurane anaesthesia (n=14) than during propofol anaesthesia (n=13) (0.3 vs 1.1 ml kg−1 h−1 [P=0.01] and 2.6 vs 6.0 mmol h−1 [P=0.04], respectively). Urinary potassium excretion was lower during anaesthesia than after, without intergroup difference (2.3 vs 5.7 mmol h−1, P<0.001). Sevoflurane anaesthesia increased plasma renin compared with baseline (138 vs 23 mIU L−1, P<0.001) and propofol anaesthesia (138 vs 27 mIU L−1, P=0.008). Plasma arginine–vasopressin did not change significantly during anaesthesia, but was elevated postoperatively compared with baseline irrespective of anaesthetic (21 vs 12 ng L−1, P=0.02). Sevoflurane caused higher postoperative plasma creatinine than propofol (83 vs 66 mmol L−1, P=0.01). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not change significantly in either group. ConclusionsSevoflurane anaesthesia reduced urine output and sodium excretion and increased plasma renin compared with propofol anaesthesia. The impact of this on acute kidney injury and fluid resuscitation during surgery warrants further investigation. Clinical trial registrationEudraCT: 2017-001646-10; Clinicaltrials.gov: NCT0333680.

Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers

The spectrum of diseases with overactive renin–angiotensin–aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography–mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (β: 0.0027; p = 4.2 × 10–7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (β: 0.0022; p = 2.1 × 10–5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.