Urinary Potassium Concentrations Research Articles

Determinants of the serum potassium concentration in chronic kidney disease.

If Ccr is creatinine clearance, a surrogate for glomerular filtration rate (GFR), the serum potassium concentration (Ks) is the sum of EK/Ccr and TRK/Ccr, which are amounts of potassium excreted and (net) reabsorbed per volume of filtrate (Ks = EK/Ccr + TRK/Ccr). We investigated changes in EK/Ccr, TRK/Ccr, and Ks through the stages of chronic kidney disease (CKD). We performed a retrospective study of 452 patients with CKD stages G1 - 5. Simultaneous measurements of serum and urine potassium and creatinine concentrations (Ks, Ku, crs, and cru) were used to calculate 1,007 individual values of EK/Ccr and TRK/Ccr as Ku×crs/cru and Ks - EK/Ccr, respectively. Mean values of EK/Ccr and TRK/Ccr were determined in CKD stages G1 - 5. Within each stage, means of the ratios were also ascertained in subsets with hyperkalemia (Ks > 5.1 mmol/L), normokalemia (Ks 3.8 - 5.1 mmol/L), and hypokalemia (Ks < 3.8 mmol/L). In comparison to values in CKD stages G1 - 2, EK/Ccr rose and TRK/Ccr fell in each higher stage. Decrements in TRK/Ccr equaled increments in EK/Ccr in G3a and G3b, and Ks remained stable. In G4 - 5, the ascent of EK/Ccr exceeded the decline in TRK/Ccr, and Ks rose accordingly. Within each CKD stage, EK/Ccr was remarkably similar in the three kalemic subsets; consequently, differences in TRK/Ccr were the sole source of differences in Ks. EK/Ccr rises and TRK/Ccr falls through the stages of CKD. Ks remains stable in stages G3a - 3b in association with equal and opposite changes in EK/Ccr and TRK/Ccr. In stages G4 - 5, Ks increases progressively because EK/Ccr rises more than TRK/Ccr falls. Within each CKD stage, differences in TRK/Ccr account entirely for differences in Ks among hyper-, normo-, and hypokalemic subsets. Causes of variability of TRK/Ccr require additional investigation.

Unveiling the Patterns of Water Diuresis in Profound Hyponatremia Management in Intensive Care Unit Settings.

Hyponatremia treatment guidelines recommend avoiding excessive increases in serum sodium concentration (s[Na]) to prevent osmotic demyelination syndrome. Although an unexpected rise in s[Na] has been attributed to water diuresis during the treatment of hyponatremia, clinical courses of water diuresis are unclear. We conducted this study to investigate the clinical characteristics of water diuresis during profound hyponatremia management. In this retrospective observational study, we examined patients with profound hyponatremia (s[Na] ≤120 mEq/L) admitted to the intensive care unit of a Japanese hospital. The manifestation of water diuresis was defined as a urine volume ≥2 ml/kg/h and a urinary sodium plus potassium concentration (u[Na+K]) ≤50 mEq/L. We analyzed changes in urine volume and u[Na+K] over time for patients experiencing water diuresis. This analysis employed a mixed-effects model with spline terms for time, and the results are graphically presented. Among 47 eligible patients, 30 (64%) met the criteria for water diuresis. The etiologies of hyponatremia were drug-related hyponatremia (n=10; 33%), primary polydipsia (n=8; 27%), hypovolemic hyponatremia (n=7; 23%), syndrome of inappropriate secretion of antidiuresis (n=7; 23%), and acute heart failure (n=1; 3%). Among patients with water diuresis, 27 (90%) experienced the manifestation of water diuresis within 24 hours after the start of correction. The increased urine volume and decreased u[Na+K] levels began several hours before the peak manifestation of water diuresis. Within 6 hours after the manifestation of water diuresis, 29 patients (97%) received electrolyte-free infusions and 14 (47%) received desmopressin. One patient (3%) with water diuresis experienced overcorrection. Water diuresis is common during the treatment for profound hyponatremia and typically occurs within the first 24 hours, preceded by changes in urinary characteristics. Early detection and prompt response to water diuresis through urine monitoring during the early periods of hyponatremia treatment may be effective for managing water diuresis.

Hypernatremia in Hyperglycemia: Clinical Features and Relationship to Fractional Changes in Body Water and Monovalent Cations during Its Development.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

Relationship between the behavior change model and salt intake in hypertensive patients: a single non-specialized hypertension clinic prospective observational study.

We investigated whether changes in salt reduction readiness are associated with changes in estimated daily salt intake and blood pressure (BP). We divided 86 hypertensive patients into groups with high and low readiness for salt-reducing behavior [an up (UP) and a down (DN) groups, respectively] based on the transtheoretical model (TTM) over a 12-month observation period. We then investigated the relationships between changes in the TTM stage and changes in daily salt intake and BP over 12 months. The patients in the UP group had significantly increased urine potassium concentrations (from 51.2 ± 23.3 mEq/L at baseline to 56.9 ± 25.5 mEq/L at 12 months; P = 0.048) and significantly decreased estimated 24-h urinary salt excretion (from 9.7 ± 2.9 g/day at baseline to 8.4 ± 2.8 g/day at 12 months; P = 0.045). In addition, they also had significantly lower changes in urine sodium concentration (-13.1 ± 46.1 vs. -6.6 ± 59.7 mEq/L; P = 0.048), significantly increased changes in urine potassium concentration (5.7 ± 20.1 vs. -4.8 ± 28.6 mEq/L; P = 0.030), and significantly decreased changes in estimated 24-h urinary salt excretion (-1.3 ± 2.6 vs. -0.1 ± 2.6 g/day; P = 0.045) compared with patients in the DN group. However, their home BP did not improve over 12 months. The hypertensive patients who increased their readiness or maintained a high readiness for salt reduction over 12 months showed a significant increase in daily potassium intake and significant decrease in daily salt intake.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.

Metabolomic Insights on Potassium Excretion, Blood Pressure, and Glucose Homeostasis: The African-PREDICT Study

BackgroundLow-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. ObjectivesUsing metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. MethodsA total of 440 White and 350 Black adults from the African-PREDICT study (aged 20–30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. ResultsBlack participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). ConclusionsRacial differences are an important consideration when investigating nutrient–metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis.This trial was registered at clinicaltrials.gov as NCT03292094.

Validation of a short food group questionnaire to determine intakes from healthy and unhealthy food groups in 5-9-year-old South African children.

Reliable dietary data for children are necessary to investigate associations with health outcomes. The present study aimed to develop and validate a questionnaire to determine the frequency of intakes of specific healthy and unhealthy food groups in young children. Participants were 5-9-year-old South African children (n = 920) from 10 urban schools. Their parents completed a demographic questionnaire and the food intake questionnaire with food pictures. Based on the literature, four healthy food groups (fruits, vegetables, milk, meat/fish/poultry/eggs) and six unhealthy food groups (hot and cold sugar-sweetened beverages, candy, salty snacks, cakes and fast foods) were included, with five different frequency responses. Six experienced nutritionists assessed the face validity and content validity. After pilot testing, construct validity and homogeneity were determined in the participants. Convergent validity was determined using urinary sodium and potassium concentrations as biological intake markers. Nutritionists confirmed face and content validity. Caregivers confirmed understanding of the questionnaire. Three factors explained 50.2% of the variance, with most unhealthy food groups as factor 1, fruits and vegetables as factor 2, and animal source protein and milk groups clustered with sugar-sweetened beverages as factor 3. The frequency of milk group, fruits and vegetables intake correlated negatively, whereas the frequency of salty snacks and fast foods intakes correlated positively with the urinary sodium:potassium ratio. The healthy and unhealthy food group questionnaire has advantages of low respondent burden, as well as acceptable content and convergent validity in South African children. The questionnaire may be used to investigate associations between food intakes and health outcomes.

Urine electrolytes do not predict desoxycorticosterone pivalate efficacy in dogs with hypoadrenocorticism.

To determine if urine electrolyte assessments can be used to monitor the adequacy of mineralocorticoid therapy in dogs with hypoadrenocorticism (HA). 29 dogs with naturally occurring glucocorticoid- and mineralocorticoid-deficient HA. Urine sodium and potassium concentrations, sodium-to-potassium ratios, sodium-to-creatinine ratios, and potassium-to-creatinine (K:Cr) ratios were evaluated in dogs with newly diagnosed HA that were treated with desoxycorticosterone pivalate (DOCP). Dogs underwent measurements of urine and serum sodium, potassium, and creatinine concentrations and plasma renin activities twice monthly for up to 3 months. Regression analyses and calculation of coefficients of determination (R2) were performed to investigate potential associations between urine and serum variables. Urine variables also were compared between dogs considered to be undertreated or overtreated based on plasma renin activities. Urine K:Cr ratios were significantly associated with serum potassium concentrations 10 to 14 days (P = .002) and 30 days (P = .027) after the initial DOCP injection, but R2 values were only 0.35 and 0.17, respectively. Urine K:Cr ratios (median [IQR]) also were higher in dogs that were overtreated with DOCP (1.3 [0.7 to 2.3]) as compared to those dogs that were undertreated with DOCP (0.8 [0.5 to 0.9]) at 10 to 14 days after the initial DOCP injection (P = .039) but not at 30 days after the initial injection. Other urine variables were not significantly different between undertreated and overtreated dogs. Measures of urine electrolytes were not useful for assessing the adequacy of mineralocorticoid therapy in HA dogs that were treated with DOCP.

Post-exercise rehydration: Comparing the efficacy of three commercial oral rehydration solutions.

This study compared the efficacy of three commercial oral rehydration solutions (ORS) for restoring fluid and electrolyte balance, after exercise-induced dehydration. Healthy, active participants (N = 20; ♀ = 3; age ∼27 y, O2peak ∼52 ml/kg/min) completed three randomised, counterbalanced trials whereby intermittent exercise in the heat (∼36°C, ∼50% humidity) induced ∼2.5% dehydration. Subsequently, participants rehydrated (125% fluid loss in four equal aliquots at 0, 1, 2, 3 h) with a glucose-based (G-ORS), sugar-free (Z-ORS) or amino acid-based sugar-free (AA-ORS) ORS of varying electrolyte composition. Urine output was measured hourly and capillary blood samples collected pre-exercise, 0, 2 and 5 h post-exercise. Sodium, potassium, and chloride concentrations in urine, sweat, and blood were determined. Net fluid balance peaked at 4 h and was greater in AA-ORS (141 ± 155 ml) and G-ORS (101 ± 195 ml) than Z-ORS (-47 ± 208 ml; P ≤ 0.010). Only AA-ORS achieved positive sodium and chloride balance post-exercise, which were greater for AA-ORS than G-ORS and Z-ORS (P ≤ 0.006), as well as for G-ORS than Z-ORS (P ≤ 0.007) from 1 to 5 h. when provided in a volume equivalent to 125% of exercise-induced fluid loss, AA-ORS produced comparable/superior fluid balance and superior sodium/chloride balance responses to popular glucose-based and sugar-free ORS.

Validation of the smartphone-based dietary assessment tool “Traqq” for assessing actual dietary intake by repeated 2-h recalls in adults: comparison with 24-h recalls and urinary biomarkers

BackgroundConventional dietary assessment methods are affected by measurement errors. We developed a smartphone-based 2-h recall (2hR) methodology to reduce participant burden and memory-related bias. ObjectiveAssessing the validity of the 2hR method against traditional 24-h recalls (24hRs) and objective biomarkers. MethodsDietary intake was assessed in 215 Dutch adults on 6 randomly selected nonconsecutive days (i.e., 3 2hR-days and 3 24hRs) during a 4-wk period. Sixty-three participants provided 4 24-h urine samples, to assess urinary nitrogen and potassium concentrations. ResultsIntake estimates of energy (2052±503 kcal vs. 1976±483 kcal) and nutrients (e.g., protein: 78±23 g vs. 71±19 g; fat: 84±30 g vs. 79±26 g; carbohydrates: 220±60 g vs. 216±60 g) were slightly higher with 2hR-days than with 24hRs. Comparing self-reported protein and potassium intake to urinary nitrogen and potassium concentrations indicated a slightly higher accuracy of 2hR-days than 24hRs (protein: −14% vs. −18%; potassium: −11% vs. −16%). Correlation coefficients between methods ranged from 0.41 to 0.75 for energy and macronutrients and from 0.41 to 0.62 for micronutrients. Generally, regularly consumed food groups showed small differences in intake (<10%) and good correlations (>0.60). Intake of energy, nutrients, and food groups showed similar reproducibility (intraclass correlation coefficient) for 2hR-days and 24hRs. ConclusionsComparing 2hR-days with 24hRs showed a relatively similar group-level bias for energy, most nutrients, and food groups. Differences were mostly due to higher intake estimates by 2hR-days. Biomarker comparisons showed less underestimation by 2hR-days as compared with 24hRs, suggesting that 2hR-days are a valid approach to assess the intake of energy, nutrients, and food groups.This trial was registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) registry as ABR. No. NL69065.081.19.

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.

Monitoring population salt intake using casual urinary sodium: Tehran Lipid and Glucose Study

BackgroundWe aimed to estimate salt intake among an Iranian population using spot urine-based equations and a dietary-based method.MethodsAdult men and women (n = 2069) were recruited from the Tehran Lipid and Glucose Study (2014–2017). Urinary sodium (Na), potassium (K), and creatinine (Cr) concentrations were measured in the morning spot urine samples. The 24-h urinary Na excretion and predicted salt intake was estimated using five equations, i.e., Kawasaki, Tanaka, Intersalt, Toft, and Whitton. A validated food frequency questionnaire (FFQ) was used to obtain dietary intake of salt. The agreement of each urinary- and FFQ-based salt estimation with the overall mean of the methods, considered as the gold standard, was assessed using the Bland–Altman method.ResultsMean age of the participants was 45.6 ± 14.8 y, and 45.4% were men. Mean (SD) estimated salt intake, derived from the overall mean of the methods, was 9.0 ± 2.2 g/d (10.2 ± 2.1 and 7.9 ± 1.7 g/d in men and women, respectively). Mean bias of the estimations from the overall mean ranged from − 0.2.42 to 2.75 g/d, with the Tanaka equation having the least bias (mean bias = 0.13 ± 1.10, 95% CI − 2.37, 2.30 g/d). Tanaka estimated a mean salt intake of 8.9 g/d (range 2.1 to 18.7 g/d); accordingly, only 5.1% of participants adhered to the recommendation (< 5 g/d salt intake), whereas 26.8% and 2.4% exceeded the recommendation by 2- and threefold.ConclusionThe Tanaka equation could provide a more accurate mean-population estimated salt intake from casual urinary Na concentration in our population. About 95% of the Iranian population exceeded the current recommendations of salt intake.

Urine uromodulin and angiotensin converting enzyme inhibitors: is there a relationship?

BACKGROUND. Uromodulin (UMO) is a multifunctional glycoprotein expressed in epithelial cells of the thick ascending part of the loop of Henle. Currently, enough information has been accumulated about the participation of this glycoprotein in a number of important physiological and pathological processes. THE AIM: to evaluate the relationship between the level of urine uromodulin (Umo) and the intake of angiotensin converting enzyme (ACE) inhibitors in chronic kidney disease. PATIENTS AND METHODS. 96 patients aged 43.6±15.4 years were examined. (M:W = 46:50). The presence of kidney disease in all cases is confirmed morphologically. The main criterion for the inclusion of patients in the study was the presence of CKD C1-C3. The exclusion criteria were age over 70 years, the presence of diabetes mellitus, immunosuppressive therapy at the time of examination, taking diuretics. Umo concentrations in blood serum (SUmo) and urine (UUmo) were measured by enzyme immunoassay. Serum and urinary concentrations of creatinine, potassium, sodium, chlorine, calcium, and inorganic phosphorus, as well as protein levels in urine, were also determined. The glomerular filtration rate (eGFR) was calculated using the formula CKD-EPI. The values of daily excretion, clearance, and fractional excretion were calculated for all ions. RESULTS. The patients were divided into two groups: group 1 – 20 people who did not take ACE inhibitors; group 2 – 78 people who took ACE inhibitors. The content of Umo in urine correlated in the first group with the value of systolic and diastolic blood pressure and serum Umo. In the second group, associations of the concentration of Umo in urine with age, eGFR, the excreted fraction of sodium and chlorine, and serum Umo were noted. CONCLUSION. The data obtained suggest that the nephroprotective properties of ACE inhibitors are broader than is commonly thought. Our data allow us to talk about their protective effect at the level of the tubular apparatus. The authors believe that the information currently available is quite sufficient to discuss the need to introduce the definitions of SUmo and UUmo into real clinical practice.

Transgenic Mice Overexpressing Human Alpha-1 Antitrypsin Exhibit Low Blood Pressure and Altered Epithelial Transport Mechanisms in the Inactive and Active Cycles.

Human alpha-1 antitrypsin (hAAT) is a versatile protease inhibitor, but little is known about its targets in the aldosterone-sensitive distal nephron and its role in electrolyte balance and blood pressure control. We analyzed urinary electrolytes, osmolality, and blood pressure from hAAT transgenic (hAAT-Tg) mice and C57B/6 wild-type control mice maintained on either a normal salt or high salt diet. Urinary sodium, potassium, and chloride concentrations as well as urinary osmolality were lower in hAAT-Tg mice maintained on a high salt diet during both the active and inactive cycles. hAAT-Tg mice showed a lower systolic blood pressure compared to C57B6 mice when maintained on a normal salt diet but this was not observed when they were maintained on a high salt diet. Cathepsin B protein activity was less in hAAT-Tg mice compared to wild-type controls. Protein expression of the alpha subunit of the sodium epithelial channel (ENaC) alpha was also reduced in the hAAT-Tg mice. Natriuretic peptide receptor C (NPRC) protein expression in membrane fractions of the kidney cortex was reduced while circulating levels of atrial natriuretic peptide (ANP) were greater in hAAT-Tg mice compared to wild-type controls. This study characterizes the electrolyte and blood pressure phenotype of hAAT-Tg mice during the inactive and active cycles and investigates the mechanism by which ENaC activation is inhibited in part by a mechanism involving decreased cathepsin B activity and increased ANP levels in the systemic circulation.

Correlation between kidney sodium and potassium handling and the renin-angiotensin-aldosterone system in children with hypertensive disorders.

Urine sodium and potassium are used as surrogate markers for dietary consumption in adults with hypertension, but their role in youth with hypertension and their association with components of the renin-angiotensin-aldosterone system (RAAS) are incompletely characterized. Some individuals with hypertension may have an abnormal RAAS response to dietary sodium and potassium intake, though this is incompletely described. Our objective was to investigate if plasma renin activity and serum aldosterone are associated with urine sodium and potassium in youth referred for hypertensive disorders. This pilot study was a cross-sectional analysis of baseline data from 44 youth evaluated for hypertensive disorders in a Hypertension Clinic. We recorded urine sodium and potassium concentrations normalized to urine creatinine, plasma renin activity, and serum aldosterone and calculated the sodium/potassium (UNaK) and aldosterone/renin ratios. We used multivariable generalized linear models to estimate the associations of renin and aldosterone with urine sodium and potassium. Our cohort was diverse (37% non-Hispanic Black, 14% Hispanic), 66% were male, and median age was 15.3 years; 77% had obesity and 9% had a secondary etiology. Aldosterone was associated inversely with urine sodium/creatinine (β: -0.34, 95% CI -0.62 to -0.06) and UNaK (β: -0.09, 95% CI -0.16 to -0.03), and adjusted for estimated glomerular filtration rate and serum potassium. Higher serum aldosterone levels, but not plasma renin activity, were associated with lower urine sodium/creatinine and UNaK at baseline in youth referred for hypertensive disorders. Further characterization of the RAAS could help define hypertension phenotypes and guide management. A higher resolution version of the Graphical abstract is available as supplementary information.

MO130GLOMERULAR FILTRATION RATE IS THE MAIN PREDICTOR OF URINE OUTPUT IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) PATIENTS TREATED WITH TOLVAPTAN

Abstract Background and Aims Tolvaptan was approved to treat autosomal dominant polycystic kidney disease (ADPKD) to slow the rate of kidney growth and renal function decline. Tolvaptan blocks the V2 vasopressin receptor in renal collecting ducts and distal nephron causing intense polyuria. Few authors have analyzed what factors influence the volume of diuresis in patients taking tolvaptan. Method We have analyzed the influence of solute excretion and glomerular filtration rate, besides age and gender as predictors of urine output, using multivariable analysis. In concret, we have searched the importance of osmolar excretion as predictor of volume of diuresis. Results We studied 24 h-urine samples from 18 ADPKD patients on treatment with tolvaptan, who had received the three doses: 45/15, 60/30 and 90/30 mg. Each patient was represented once per dose, for a total of 54 urine samples (Table 1). Tolvaptan increased urine volume, which was roughly doubled, and roughly halved urine solute concentrations expressed by volume and calculated osmolality. By contrast, solute concentrations expressed as ratios with creatinine remained constant as did osmolality corrected with urinary creatinine, indicating that there was no change in solute excretion after tolvaptan. Urine volume was correlated with serum creatinine (Rho= -0.36, p= 0.008), urinary creatinine (Rho = -0.29, p = 0.034) and GFR-MDRD4 (Rho = 0.44, p= 0.001). Urine volume was correlated with calculated daily osmolar excretion in Osm/day (Rho = 0.76, p &amp;lt;0.001). Urine volume was not correlated with calculated urinary osmolality in mOsm/Kg (Rho= -0.04, p= 0.77) or as urinary osmolality/creatinine ratio (Rho= 0.23, p= 0.1). Correlation of urine volume with osmolar excretion was lost when urine volume was removed from the predictor variable. Urine volume was additionally not correlated with urinary urea o sodium concentrations nor their solute/creatinine ratios, and although it was correlated with urinary potassium concentration (Rho = -0.33, p=0.014), it was not correlated with potassium/creatinine ratio. We also performed a linear regression analysis searching predictors of urine volume. Only GFR and the osmolality/creatinine ratio were significant predictors of urine volume (urine volume= 55.35 x GFR + 4.74 x Osmolality/Cr; r2= 0.41, p&amp;lt;0.001) but individual solute assessments or tolvaptan dose did not predict urine volume. Conclusions Therefore, urine volume after initiating tolvaptan in patients with ADPKD is influenced mainly by the degree of renal function. There might also be a contribution of urinary solute load but it can not be studied using total solute excretion due to collinearity. We propose that the urinary solute/creatinine ratio and osmolality/creatinine ratio should be used to search for predictors of urine output in patients on tolvaptan.

Retrospective Observational Study on Predictors of Body Weight and BNP Teduction in Cases of Tolvaptan Induction for Heart Failure

Tolvaptan (TLV) carries the risk of serious side effects, and its introduction requires hospitalization. Therefore, it is important from the viewpoints of safety and medical economics to predict in advance, the patients for whom it will be effective and introduce it. The purpose of this study was to investigate the noninvasive and simple predictors for identifying TLV responders. We conducted a retrospective observational study of patients with heart failure who had TLV introduced at our hospital from January 1, 2017, to December 31, 2018. By using the body weight and BNP reduction as the effect indices, predictors of body weight and BNP reduction were extracted by logistic analysis. The sensitivity and specificity at the cutoff value obtained by ROC analysis were also examined. Among 85 subjects, urine sodium concentration >63 mEq/L [odds ratio (OR): 6.11, 95% confidence interval (CI): 1.36-27.4] was detected as a predictor of body weight reduction. The sensitivity at this cutoff value was 81%, and the specificity was 70%. Serum osmolarity>291 mOsm/L (OR: 3.76, 95% CI: 1.00-14.2), urine potassium concentration<21 mEq/L (OR: 4.45, 95% CI: 1.09-18.2), and urine sodium concentration>71 mEq/L (OR: 7.38, 95% CI: 2.05-26.6) were detected as predictors of BNP reduction. The sensitivities were 62%, 53%, and 73%, and the specificities were 58%, 68%, and 68%, respectively. Therefore, it was suggested that urine sodium concentration may be useful as a predictor of body weight and BNP decrease after TLV induction.

Potassium excretion and blood pressure are associated with heart rate variability in healthy black adults: The African-PREDICT study

Background and aimsHeart rate variability (HRV) is a main determinant of autonomic function and related to the development of hypertension and cardiovascular (CV) disease. Hypertension develops in black populations at an earlier age, which could be due to differences in the autonomic nervous system activity and sodium/potassium handling in black and white populations. We investigated whether HRV is associated with 24 h urinary sodium and potassium excretion and blood pressure (BP) in a young bi-ethnic cohort. Methods and resultsWe examined 423 black and 483 white healthy adults (aged 24.5 ± 3.1 years) for 24 h HRV, including standard deviation of normal RR intervals (SDNN) reflecting autonomic variations over time, and root mean square of successive differences (RMSSD) reflecting parasympathetic activity. We measured 24 h urinary sodium and potassium concentration and BP. The black group had lower SDNN and potassium excretion as well as higher RMSSD, sodium and Na/k ratio compared to the white group (all p < 0.05). Only in black individuals, urinary potassium excretion was independently and negatively associated with SDNN (β[95% CI];-0.26[-0.50;-0.02]ms) and RMSSD (−0.14[-0.27;-0.01]ms, p < 0.05). One unit increase in sodium/potassium (Na/K) ratio was associated with higher SDNN (β[95% CI]; 3.04[0.89; 5.19]ms) and RMSSD (1.60[0.41; 2.78]ms) in the black cohort only (both p < 0.001). In both groups elevated 24 h diastolic BP was associated with lower RMSSD (p < 0.05). ConclusionLower potassium excretion and higher Na/K ratio related independently to higher HRV in young and healthy black adults. A better ethnic-specific understanding of sodium and potassium handling is required as part of preventive cardiology, especially in black individuals. Clinical trial registrationClinicalTrials.gov Identifier: NCT03292094; URL: https://clinicaltrials.gov/ct2/show/NCT03292094.

Discrepant acute effect of saline loading on blood pressure, urinary sodium and potassium according to salt intake level: EpiSS study.

Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24‐hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24‐hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose‐response association between SBP increment with 24hUNa (β = −0.901, 95% CI: −1.253, −0.548), especially in lower salt intake individuals (β = −1.297, 95% CI: −2.338, −0.205) and hypertensive patients (β = −1.502, 95% CI: −2.037, −0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations.

Effect of empagliflozin as add-on therapy on transtubular potassium concentration gradient in patients with type 2 diabetes hospitalized for acute decompensated heart failure

Abstract Background The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity, and has been shown to be a surrogate of arterial underfilling in patients with acute decompensated heart failure (ADHF). Moreover, high TTKG at discharge has been shown to be associated with poor prognosis in ADHF patients. Empagliflozin, one of the sodium glucose cotransporter 2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease. However, little is known about the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Methods We enrolled 58 consecutive T2D patients admitted for ADHF. On admission, enrolled patients were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All patients in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. The TTKG was measured using the first morning urine samples collected on each day. TTKG was calculated according to the following equation: TTKG = (Ku/Ks)×(plasma osmolality/urine osmolality), where Ku is urine potassium concentration and Ks is serum potassium concentration, as previously reported. Results Thirty patients were assigned to the EMPA(+) group, and 28 patients were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma B-type natriuretic peptide (BNP) level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. TTKG did not significantly differ between the two groups at baseline. However, seven days after randomization, plasma BNP level was significantly lower in the EMPA(+) group than in the EMPA(−) group (median 227 [IQR 114–381] pg/mL vs 362 [227–554] pg/mL, p=0.0294). Furthermore, TTKG of the EMPA(+) group was significantly lower at 2, 3 and 7 days after randomization (Figure). Conclusions This study demonstrated that empagliflozin as add-on therapy can lower TTKG in T2D patients with ADHF. Figure 1 Funding Acknowledgement Type of funding source: None