Urinary Sodium Excretion Research Articles

Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial.

Cardiorenal dysfunction with impaired cyclic GMP (cGMP) response is common in patients presenting with acute heart failure (HF). Type V phosphodiesterase (PDEV) is known to be upregulated in HF and may explain the dysfunction of renal response. The aim of this study was to determine whether B-type natriuretic peptide (BNP) alone or in combination with PDEV inhibition improves renal function and increases urinary sodium and cGMP excretion in acute HF. This open-label study included 67 patients hospitalized with acute HF and renal dysfunction. Patients were randomized to standard care, low-dose intravenous BNP (0.005 µg/kg per minute), or combination BNP/PDEV inhibition with sildenafil (25 mg q12 hours) for 48 hours. The coprimary end points were the percent change in estimated glomerular filtration rate and blood urea nitrogen from baseline to 48 hours. Treatment with BNP and BNP/PDEV inhibitor significantly increased plasma cGMP at 24 hours (+25.6% [+9.8%, +84.7%] and +60.8% [+32.3%, +103.8%] for BNP and BNP/PDEV versus -13.5% [-29.1%, +14.2%] with standard care; P=0.001). However, there was no significant change in estimated glomerular filtration rate 0 (-10.8%, +12.7%) for standard care versus 0 (-15.3%, +11.8%) for the BNP group versus -8.8% (-14.3%, +8.3%) for the BNP/PDEV group (P=0.60) or blood urea nitrogen -1.4% (-10.7%, +12.0%) for standard care versus -5.9% (-14.6%, +9.4%) for the BNP group versus +6.9% (-5.3%, +18.8%) for the BNP/PDEV group (P=0.38) between groups. Hypotension was more common in the BNP/PDEV inhibitor group. BNP and combination BNP/PDEV inhibition increased plasma cGMP in patients with acute HF but did not improve renal function or urinary sodium/cGMP excretion. Our study does not support the use of intravenous low-dose BNP with or without PDEV inhibition to enhance renal function in patients admitted with acute HF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00972569.

Persistent renal dysfunction post-chemotherapy: a diagnostic conundrum in pediatric cancer survivorship – a case report

BackgroundLate-onset type II Bartter syndrome is an exceedingly rare condition, with only six documented cases presenting symptoms and signs beyond infancy. We report a unique case of late-onset type II Bartter syndrome with an atypical presentation and clinical course following chemotherapy treatment during childhood.Case presentationA 10-year-old boy, diagnosed with hepatoblastoma at age 2 and treated with cisplatin and epirubicin, presented with polyuria, polydipsia, failure to thrive, and electrolyte imbalances. He exhibited hypokalemia, metabolic alkalosis, and elevated urinary excretion of sodium, chloride, calcium, and magnesium. Whole exome sequencing and Sanger sequencing identified compound heterozygous variants in the KCNJ1 gene, confirming the diagnosis of type II Bartter syndrome. The patient’s clinical presentation was distinct from previously reported cases, with an absence of nephrocalcinosis, unusually small and hyperechoic kidneys, and a substantial decline in kidney function. Treatment included oral potassium supplementation, spironolactone, and angiotensin-converting enzyme inhibitors.ConclusionsThis case highlights the importance of considering late-onset Bartter syndrome in patients with a history of chemotherapy presenting with persistent electrolyte imbalances and ongoing renal dysfunction. The atypical features and rapid progression of chronic kidney disease in this patient may be attributed to the deleterious nature of the identified variants and the potential impact of previous chemotherapy on kidney susceptibility to damage. Careful monitoring and management of electrolyte imbalances and renal function are crucial in such cases.

Blood pressure and cardiovascular risk in relation to birth weight and urinary sodium: an individual-participant meta-analysis of European family-based population studies

Abstract Background While the relation of salt intake with blood pressure (BP) is linear, it is U-shaped for mortality and cardiovascular disease (CVD). Purpose This individual-participant meta-analysis explored whether the relation of hypertension, death or CVD with 24 h urinary sodium excretion (UVNA) or sodium-to-potassium (UNAK) ratio was modified by birth weight. Methods Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001). Categories of birth weight, UVNA and UNAK (≤2500, >2500-4000, >4000 g; <2.3, 2.3-4.6 and >4.6 g; and <1, 1-2 , >2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan-Meier survival functions and linear and Cox regression. Results The study population was subdivided into the Outcome (n=1945), Hypertension (n=1460) and BP cohorts (n=1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome Cohort was 5.8/84.5/9.7%. Over 16.7 years (median), rates were 4.9%, 8.0% and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-adjusted hazard ratios were not significant for any endpoint in any of the BW, UVNA and UNAK strata. Adult body weight tracked with birth weight (P<0.0001). The partial r in the low birth weight group associating changes from baseline to follow-up in UVNA and systolic BP was 0.68 (P=0.023), but not significant in other birth weight groups. Conclusion This study did not substantiate its prior hypothesis, but showed tracking of adult with birth weight and suggest that low birth weight increases salt sensitivity.Figure 1Figure 2

Multiparametric assessment of decongestion in patients admitted with acute heart failure: dynamic changes and correlation with natriuresis

Abstract Background Heart Failure (HF) is a major public health problem, expected to increase in the next few decades. The vast majority of acute HF (AHF) episodes are precipitated by congestion with volume overload and/or fluid redistribution. Current Guidelines stress on the importance of relieving congestion before discharge, recommending anyway only daily assessment of signs and symptoms. Lung ultrasound (LUS) B-lines and other ultrasound markers of congestion has emerged as valuable tools to improve diagnostic accuracy and help clinicians in fluid management. Purpose To assess the dynamic changes of B-lines and other markers of congestion and their relationship with the clinical evaluation, chest X-ray (CXR) and natriuretic peptides in patients admitted for AHF. Methods Fifty-eight patients (age 72±11 ys, 35% women) admitted with acute HF were enrolled. Patients underwent clinical evaluation (Clinical Congestion Score, CCS, including rales, pathological S3 heart sound, pedal oedema, jugular vein distension; range 0-4), and CXR (CXR score, including enlargement and loss of definition of hilar structures, peribronchial and perivascular cuffing, cardiomegaly, pleural effusion; range 0-4). An integrated multiorgan ultrasound exam including LUS B-lines, echocardiography, and venous excess ultrasound (VExUS) score was performed at admission (T0), between 24 and 48 hours from T0 (T1), and at discharge (T2). Follow-up data at 30 days were collected. Results Mean CCS was 1.52±0.99 at T0, with a reduction at T1 (0.86±0.66; p<0.01), and at T2 (0.34±0.66; p<0.01). Sixteen percent of patients with a CCS=0 at T0 showed, however, persistent B-lines on LUS (mean B-lines 19±6). The mean number of B-lines was 26±12 at T0 with a reduction at T1 (17±11; p<0.001), and at T2 (13±11; p<0.001). Other echocardiographic non-invasive hemodynamic parameters, such as pulmonary artery systolic pressure (PASP) and E/e’ showed a reduction only at T2, but not at T1 (figure). The number of B-lines correlated at all time points with CCS, CXR score, VExUS score, and NT-proBNP values (all p<0.05). We divided patients into two groups: "responders" (with ≥15 reduction of B-lines between T0 and T2) and "non-responders" (with <15 reduction of B-lines between T0 and T2). Responders had higher chlorine and sodium urinary excretion at T1 compared to non-responders. The number of B-lines at all time points was associated to 30-days cardiovascular mortality at univariable analysis. Neither CCS nor CXR score were associated with 30-day events. Conclusions In patients with acute HF, B-lines quantification is related to standard congestion assessment based on clinical evaluation, CXR and NT-proBNP, showing, however, a more dynamic behaviour in the assessment of decongestion. B-lines variations are also related to diuresis and chlorine urinary output, a recognized predictor of diuretic response. Persistent congestion is related to an increased risk of hospitalization and death.

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves

Salt-related knowledge, attitudes, and practices and their relationship with 24-hour urinary sodium and potassium excretions among a group of healthy residents in the UAE: A cross-sectional study.

This study aimed to measure urinary sodium and potassium as a measure of sodium and potassium intake concerning the knowledge, attitude, and practice (KAP) toward sodium intake among a group of healthy residents in the UAE. A cross-sectional study on a sample of healthy adults in the UAE. In addition to the KAP questionnaire, sodium and potassium excretions, and food records were taken. The United Arab Emirates. A sample of 190 healthy individuals aged between 20-60 years. The mean (± SD) age of the sample was 38.6 (± 12.5) years and 50.5% were females. The mean urinary sodium and potassium intake were 2816.2± 675.7 mg /day and 2533.3± 615 mg/day, respectively. The means were significantly different compared to the World Health Organization (WHO) recommendation of sodium and potassium, (p < 0.001). About 65% of the participants exceeded the WHO recommendations for salt intake, and participants' knowledge classification for health-related issues was fair while food-related knowledge was poor (P=0.001). A two-stage stepwise multiple regression analysis revealed that KAP scores were negatively associated with urinary sodium excretion (r = -0.174; p = 0.017) and those older participants and females had lower urinary sodium excretion (p<0.001). These findings may suggest an increase in the risk of hypertension in the UAE population. Moreover, these findings emphasize the need to establish education and public awareness programs focusing on identifying the sodium contents of foods and establishing national regulations regarding food reformulation, particularly for staple foods such as bread.

Study on the antihypertensive mechanism of acupuncture at "Renying" (ST9) and "Zusanli" (ST36) via gastrin/cholecystokinin B receptors

To observe the effect of acupuncture on serum gastrin content and urinary sodium excretion in spontaneously hypertensive rat (SHR), so as to explore its potential mechanism in the treatment of hypertension. Thirty-two male SHRs were randomly divided into model, hydrochlorothiazide, acupuncture and sham acupuncture groups, with 8 rats in each group, and 8 male Wistar-kyoto rats were taken as the control group. Rats in the hydrochlorothiazide group received gavage of hydrochlorothiazide solution (10 mg·kg-1·d-1), once daily for 4 weeks. Acupuncture was applied to bilateral "Renying" (ST9) and "Zusanli" (ST36) or non-acupoint on both sides for rats in the acupuncture and sham acupuncture groups, with manual stimulation every 10 minutes for a total of 20 minutes, once a day for a total of 4 weeks. The systolic blood pressure of the tail-artery was measured before and 1, 2, 3, and 4 weeks after the intervention. HE staining was used to observe the pathological changes in renal tissue. Serum gastrin contents were detected using enzyme-linked immunosorbent assay (ELISA). Urinary sodium content was measured by atomic absorption spectrometry. The expression levels of cholecystokinin B receptor (CCKBR) and Na+/K+-ATPase proteins in renal tissue were detected by Western blot, and the mRNA expression levels of CCKBR and the α1 subunit of Na+/K+- ATPase (ATP1A1) were detected by fluorescence quantitative PCR. Compared with the control group, the systolic blood pressure of the tail artery in the model group were increased significantly before intervention and at the 1st, 2nd, 3rd and 4th weeks of intervention (P<0.05). Before intervention, the 24 h urine volume of the model, hydrochlorothiazide, acupuncture and sham acupuncture groups were decreased significantly (P<0.05). After intervention, the 24 h urine volume and urinary sodium excretion in the model group were significantly decreased (P<0.05)；the expression levels of CCKBR protein and mRNA in renal tissue were significantly decreased (P<0.05)；the expression levels of Na+/K+-ATPase protein and ATP1A1 mRNA were significantly increased (P<0.05)；the glomerulus was mildly congested with a small amount of lymphocyte infiltration. Compared with the model group, the systolic blood pressure of the tail artery in the hydrochlorothiazide and the acupuncture groups were decreased significantly at the 2nd, 3rd and 4th weeks of intervention (P<0.05)；the 24 h urine volume and urinary sodium excretion in the hydrochlorothiazide and the acupuncture groups were significantly increased (P<0.05)；the serum gastrin content and the expression levels of CCKBR protein and mRNA in renal tissue were significantly increased (P<0.05)；the expression levels of Na+/K+-ATPase protein and ATP1A1 mRNA were significantly decreased (P<0.05)；there were no obvious pathological changes in renal tissue. A small number of lymphocyte focal infiltration around blood vessels was observed in the kidney tissue of the sham acupuncture group. Acupuncture can significantly reduce the tail artery systolic blood pressure of SHR, which may be related to its effect in increasing serum gastrin content and CCKBR expression, inhibiting sodium pump reabsorption, thus promoting urinary sodium excretion.

Short Term Treatment Monitoring of Renal and Inflammatory Biomarkers with Naturally Occurring Leishmaniosis: A Cohort Study of 30 Dogs

Various inflammatory and renal biomarkers have already been assessed for monitoring the response to anti-leishmanial therapy in canine leishmaniosis. This study assessed the parasite load, various inflammatory and renal biomarkers pre- and post-treatment, and any association between the studied variables and the degree of disease severity at diagnosis. This is a prospective cohort study of 30 client-owned dogs with leishmaniosis, classified according to LeishVet’s guidelines as stage I (n = 2), stage IIa (n = 7), stage IIb (n = 6), stage III (n = 8), and stage IV (n = 7). In addition to Leishmania real-time PCR in the bone marrow, blood and urine, previously studied biomarkers, and several inflammatory and renal markers never investigated in canine leishmaniosis, such as fibrinogen, antithrombin, urinary fractional excretion of sodium, and urinary amylase-to-creatinine ratio were measured pre- and post-treatment (meglumine antimoniate or miltefosine + allopurinol). A positive Leishmania real-time PCR in the blood at diagnosis predicted a positive Leishmania real-time PCR in the bone marrow post-treatment (p = 0.003). Following treatment, antithrombin and urinary amylase-to-creatinine ratio were significantly changed (p &lt; 0.001, respectively). Urinary amylase-to-creatinine ratio, total iron-binding capacity, and antithrombin were the variables most strongly associated with disease severity (p &lt; 0.005, respectively). Urinary amylase-to-creatinine ratio can be a useful marker to monitor treatment response and to classify the degree of disease severity.

Association of Urinary Sodium, Potassium, and the Sodium-to-Potassium Ratio with Impaired Kidney Function Assessed with 24-H Urine Analysis.

Background: Albuminuria and albumin excretion rate (AER) are important risk factors for chronic kidney disease (CKD) development. Despite the extensive evidence of the influence of sodium and potassium on cardiovascular health, the existing evidence regarding their impact on albuminuria and kidney disease is limited and inconsistent. Our study aimed to assess the correlation between urinary sodium and potassium excretion, and the sodium-to-potassium ratio (Na/K ratio) with impaired kidney function, particularly the AER and albuminuria. Materials and Methods: Data were collected from the Lithuanian NATRIJOD study. A total of 826 single 24-h urine samples from individuals aged 18 to 69 were collected and analyzed for their sodium and potassium levels, Na/K ratio, and AER. Albuminuria was defined as an AER exceeding 30 mg/24 h. Results: The participant mean age was 47.2 ± 12.1 years; 48.5% of the participants were male. The prevalence of albuminuria was 3%. Correlation analysis revealed a positive correlation between AER and urinary sodium excretion (rs = 0.21; p < 0.001) and urinary potassium excretion (rs = 0.28; p < 0.001). In univariate linear regression analysis, sodium and potassium excretion and the Na/K ratio were significant AER predictors with β coefficients of 0.028 (95% CI: 0.015; 0.041; p < 0.001), 0.040 (95% CI: 0.003; 0.077; p = 0.035), and 1.234 (95% CI: 0.210; 2.259; p = 0.018), respectively. In the multivariable model, only urinary sodium excretion remained significant, with a β coefficient of 0.028 (95% CI: 0.016; 0.041). Potential albuminuria predictive factors identified via univariate logistic regression included urinary sodium excretion (OR 1.00; 95% CI: 1:00; 1.01) and the Na/K ratio (OR 1.53; 95% CI: 1.11; 2.05). However, these factors became statistically insignificant in the multivariate model. Conclusions: Urinary sodium and potassium excretion and the Na/K ratio are significantly associated with kidney damage, considering the assessed 24-h albumin excretion rate and presence of albuminuria content.

Antiurolithic activity of Zaleya pentandra (L.) C Jeffrey in ethylene glycol-induced calcium oxalate crystal rat model; A scientific validation of traditional use for kidney stone prevention

Ethnopharmacological relevanceTraditional herbal remedies have been used for treating nephrolithiasis, but the relevant scientific evidence is limited. Zaleya pentandra (L.) C. Jeffrey is traditionally used for the prevention of kidney stones in various cultures. However, its efficacy has not been scientifically studied. Aim of the studyThis study aimed to investigate the antiurolithic activity of Zaleya pentandra, and validate its traditional used for preventing kidney stones. Materials and methodsThe crude ethanolic extract of Z. pentandra (Zp.Crd) was evaluated through in vitro and in vivo studies. In vitro experiments assessed its impact on crystal count and morphology in metastable calcium oxalate solutions. In vivo studies involved diuretic and ethylene glycol-induced calcium oxalate crystal formation in male Wistar rats. ResultsZp.Crd transforms calcium oxalate crystals from harmful calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD). In vivo, Zp.Crd exhibited dose-dependent (30–300 mg/kg) diuretic activity in rats by significantly increasing urinary sodium (Na+) and potassium (K+) excretion, similar to the standard diuretic hydrochlorothiazide (HCT). In the urolithiasis model, Zp.Crd exhibited dose-dependent antiurolithic effects by reducing kidney crystals and significantly altering lithogenic factors induced by ethylene glycol, including crystalluria, oxaluria, calcium, creatinine, and urea, in the urine and serum of treated rats. Zp.Crd also exhibited antioxidant effects, effectively combating oxidative lithogenic stress in rats. ConclusionZp.Crd has been shown to demonstrate antiurolithic activity against CaOx stones through CaOx crystal inhibition, diuretic activity, antioxidant properties, hypocalciuric effects, and hypercitrauric actions. The findings underscore Zp.Crd's potential as a viable alternative or supplemental therapy to current urolithiasis treatments, paving the door for further clinical trials and its inclusion into modern medical practices.

Lower Fractional Excretion of Urinary Sodium among Patients with Muddy Brown Granular Casts Does Not Portend Lesser AKI Severity

Lower Fractional Excretion of Urinary Sodium among Patients with Muddy Brown Granular Casts Does Not Portend Lesser AKI Severity

Rho-associated, coiled-coil-containing protein kinase 2 regulates expression of mineralocorticoid receptor to mediate sodium reabsorption in mice

The mineralocorticoid receptor (MR) is a member of the nuclear receptor family that was initially identified to regulate blood pressure through its ability to modulate kidney sodium handling in response to aldosterone. MR can be regulated by signals other than aldosterone; however, the detailed mechanisms remain to be elucidated. We found that MR is controlled in a Rho-associated coiled-coil-containing protein kinase 2 (ROCK2)-dependent manner. Mice with a specific deletion of ROCK2 in the kidney tubules showed decreased MR expression levels and increased urinary excretion of sodium. Mechanistically, signal transducer and activator of transcription 3 (STAT3) is a key molecule that mediates MR expression in these mice. This study highlights an important role of tubular ROCK2 in electrolyte homeostasis.

Endothelin receptor B is required for the blood pressure-lowering effect of G protein-coupled estrogen receptor 1 in ovariectomized rats.

Activation of G protein-coupled estrogen receptor 1 (GPER1) elicits antihypertensive actions in different animal models. The endothelin-1 signaling system plays a fundamental role in blood pressure regulation. Lack of functional endothelin receptor B (ETB) evokes hypertension and salt sensitivity. GPER1 and ETB interact to promote urinary sodium excretion in female rats. We hypothesized that activation of GPER1 protects against hypertension and salt sensitivity induced by ETB antagonism in female rats. Female Sprague-Dawley rats were implanted with radiotelemetry. Animals were then subjected to ovariectomy and simultaneously implanted with minipumps to deliver either the GPER1 agonist G1 or its corresponding vehicle. Two weeks post surgery, we initiated treatment of rats with the ETB antagonist A-192621. Animals were maintained on a normal-salt diet and then challenged with a high-salt diet for an additional 5 days. Assessment of mean arterial blood pressure revealed an increase in vehicle-treated, but not G1-treated, rats in response to ovariectomy. A-192621 increased blood pressure in normal-salt diet-fed vehicle- and G1-treated rats. G1 improved the circadian blood pressure rhythms that were disrupted in A-192621-treated ovariectomized rats. Thus, although systemic GPER1 activation did not protect ovariectomized rats from hypertension and salt sensitivity induced by ETB antagonism, it maintained circadian blood pressure rhythms. Functional ETB is required to elicit the antihypertensive actions of GPER1. Additional studies are needed to improve our understanding of the interaction between G protein-coupled receptors in regulating circadian blood pressure rhythm.NEW & NOTEWORTHY Systemic G protein-coupled estrogen receptor 1 (GPER1) activation in rats prevents the increase in blood pressure evoked by ovariectomy. Blockade of endothelin receptor B negates the blood pressure-lowering impact of GPER1 in ovariectomized rats. Endothelin receptor B plays an important role in mediating the blood pressure-lowering action of GPER1 activation in female rats.

Community-level dietary intake of sodium, potassium, and sodium-to-potassium ratio as a global public health problem: a systematic review and meta-analysis

Background: Widespread adoption of a westernized diet represents a major lifestyle change characterized by substantially higher sodium consumption and lower potassium intake, which is related to cardiovascular morbidity. Methods: We performed a systematic review and meta-analysis over published studies in accordance with quantifying the dietary intake of sodium and potassium of the universal population across the world. The PubMed, EMBASE, Cochrane Library, and Google Scholar databases were used to find research that pronounced 24-hour urinary sodium or potassium excretion (reference period: 2014–2021). The effect size was estimated using the fixed-effect model; sub-group analysis become accomplished to determine urinary sodium and potassium excretion disaggregated by geographical location. Publication bias became evaluated the usage of graphical funnel plot. Data analysis was performed using STATA 16. Results: Forty-three studies (n= 62,940) qualified the selection criteria. The mean urinary excretion of sodium and potassium was 156.73 mmol/24h [95% confidence interval (CI), 148.98–164.47] and 48.89 mmol/24 h (95% CI, 43.61–54.17), respectively; the mean urinary sodium/potassium ratio was 3.68 (95% CI, 2.96–4.40). Conclusions: This updated systematic review highlights excessively high dietary intake of sodium and low intake of potassium at the community level in most parts of the world. The urinary Na/K ratio exceeded the level recommended by the WHO guidelines.

Volume Status among Hyponatremic admitted Patients

Introduction: The kidneys play a vital role in the management of hyponatremic patients with fluid disturbances. This task becomes more challenging in presence of comorbidities like chronic kidney disease or congestive heart failure. Accurate assessment of volume status and urinary sodium excretion is essential part for the correct management.. Both impaired renal function and compromised left ventricular function complicate the accurate evaluation of a patient's fluid status. Method: This cross-sectional prospective study was conducted over 262 adult patients with hyponatremia at The Indus Hospital, Karachi from 2017 to 2020. The patient's volume status at the time of enrollment was categorized as normovolemic, hypovolemic, or hypervolemic based on clinical examination. Spot urine sodium, chloride, potassium, urine and serum osmolality, serum urea, and Random blood sugar were all done. Results: There was a total of 262 patients in which 123 (46.9%) were male and 139 (53.1%) were female. The mean age was 54.1 ± 16.4 years. The overall comorbid burden was high 227(86.64%), in which hypertension and CKD contributed more. Out of 262 patients, half of them suffered from hypovolemia 131(50%). Spot urine sodium (&gt;20 meq) was found in 219(83.58/%) patients, in which predominant volume status was hypovolemia 104(47.5%). Moreover, among those who could not survive were 28 (10.7%), in which hypovolemia contributed more than other volume status 12(42.85%). Conclusion: Hypovolemia came out to be the predominant volume status among hyponatremic patients with high comorbid burden. Majority excreted more sodium in spot urine sample despite of hypovolemia in majority.

Urinary Sodium Excretion and Kidney Disease Progression in IgA Nephropathy: A Cohort Study

Introduction: The role of dietary sodium intake in the risk of chronic kidney disease progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy. Methods: We assessed 596 patients with IgA nephropathy, and urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure. Results: After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln-transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR: 2.1; 95% CI: 1.4–3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI: 1.0–3.4) for the second tertile and 2.1 (95% CI: 1.1–3.9) for the third tertile. Conclusion: Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics.

Twenty-four hour urinary sodium and potassium excretion in adult population of Slovenia: results of the Manjsoli.si/2022 study.

The objective of study was to assess 24-h urinary Na and K excretion and estimate the average salt and K intakes in a nationally representative sample of the adult population of Slovenia. A nationally representative cross-sectional study was conducted in four stages between September and November 2022: study questionnaire, physical measurements, 24-h urine collection and laboratory analysis. Slovenia. We invited 2000 adult, non-institutionalised inhabitants of Slovenia, aged between 25 and 64 years. A stratified two-staged sample was selected from this population by the Statistical Office of Slovenia, using sampling from the Central Population Register. According to the WHO methodology, additional eligibility criteria were screened before participating. A total of 518 individuals participated in all four stages of the study, resulting in a response rate of 30 %. The mean 24-h urinary Na excretion was 168 mmol/d (95 % CI 156, 180), which corresponds to a mean estimated intake of 10·3 g salt/d (95 % CI 9·6, 11·1). Mean 24-h urinary K excretion was 65·4 mmol/d (95 % CI 63·2, 67·5), and the estimated mean K intake was 2·93 g/d (95 % CI 2·84, 3·03). There were statistically significant differences in mean intakes between males and females. The mean sodium-to-potassium ratio was 2·7 (95 % CI 2·5, 2·8). The study results highlighted that the salt intake in the adult population of Slovenia remains much higher than recommended by the WHO, and K intakes are insufficient, as most participants did not meet the recommendations.

Left ventricular structure and function in relation to sodium dietary intake and renal handling in untreated Chinese patients.

Whether left ventricular structure and function is associated with sodium dietary intake and renal handling while considering blood pressure (BP) remains unclear. Consecutive untreated patients referred for ambulatory BP monitoring were recruited. Standard echocardiography was performed to measure left ventricular structure and function. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal tubular sodium handling, respectively. The 952 participants (51.0% women; mean age, 50.8 years) included 614 (64.5%) ambulatory hypertension and 103 (10.8%) left ventricular hypertrophy. There were significant interactions of urinary sodium excretion with FELi (P ≤ 0.045), but not FDRNa (P ≥ 0.36), in relation to left ventricular posterior wall thickness (LVPW), mass (LVM) and mass index (LVMI), but not functional measurements. Only in tertile 1 of FELi, the multivariate-adjusted regression coefficients for urinary sodium excretion reached statistical significance (P ≤ 0.049), being 0.16 ± 0.05 mm, 4.32 ± 1.48 g, and 1.64 ± 0.83 g/m2 for LVPW, LVM and LVMI, respectively. In mutually adjusted analyses, the regression coefficient for LVMI was statistically significant for FELi, FDRNa and 24-h systolic BP, being -2.17 ± 0.49, -1.95 ± 0.54, and 2.99 ± 0.51 g/m2, respectively (P < 0.001). Multivariable analysis of variance showed that sodium renal handling indexes (P ≥ 0.14), but not sodium urinary excretion (P = 0.007), were similarly as 24-h BP associated with LVMI. Heat maps on left ventricular hypertrophy provided a graphical confirmation of the findings. Sodium dietary intake and renal handling interact to be associated with left ventricular structure. Renal handling indexes were similarly in size as, jointly in action with and independently of 24-h BP.

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor.

In patients with heart failure (HF) who respond inadequately to loop diuretic therapy, BMS-986308, an oral, selective, reversible renal outer medullary potassium channel (ROMK) inhibitor may represent an effective diuretic with a novel mechanism of action. We present data from the first-in-human study aimed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following single ascending doses of BMS-986308 in healthy adult participants. Forty healthy participants, aged from 20 to 55 years, and body mass index (BMI) from 19.8 to 31.6 kg/m2 were assigned to 1 of 5 dose cohorts (1, 3, 10, 30, and 100 mg) and randomized (6:2) to receive BMS-986308 oral solution or matching placebo. Following administration, BMS-986308 was rapidly absorbed with a median time to maximum concentration (Tmax) of 1.00 to 1.75 h and exhibiting a mean terminal half-life (t1/2) of approximately 13 h. Dose proportionality was evident in BMS-986308 area under the concentration-time curve (AUC), while maximum concentration (Cmax) was slightly greater than dose-proportional. We observed that urine output (or diuresis; mL) and urinary sodium excretion (or natriuresis; mmol) increased in a dose-dependent manner, starting at a minimum pharmacologically active dose of 30 mg. The largest mean changes from baseline in diuresis and natriuresis occurred in both the 6- and -24 h post-dose period following administration of 100 mg (1683.0 mL and 2055.3 mL, and 231.7 mmol and 213.7 mmol, respectively; ***P < 0.001). Overall, single-dose BMS-986308 was found to be safe, well-tolerated, with an excellent PK profile, and substantial diuretic and natriuretic activity.

Development and validation of a prediction model for estimating 24-Hour Urinary Sodium Excretion using spot urine samples in adult patients

To assess whether 24-h urinary sodium excretion (24uNa) can be estimated from spot samples in adult patients who attend hospital clinics. Methods: A cross-sectional study with a development (284 patients) and a validation cohort (229 patients) was conducted at our hospital. A multivariate linear regression model was built which was compared with former models. Concordance analyses and comparison of the ability to correctly classify each patient against a prespecified uNa cut-off value of 130 mmol/24h were performed, assessed by the C-statistic. The model was well calibrated (slope [95%CI] in internal validation: 0.965 [0.947-0.987], showing good discrimination, and performed robustly in an external validation cohort (slope: 0.811 [0.675-0.946]). The mean bias between the measured and the estimated 24uNa by NaRYC was 24.85 mmol/24h [17.06-32.63]. The NaRYC had the highest values of Pearson coefficient (0.613 p<0.0001), accuracy (P30): 56.8%, and AUC-ROC: 0.822 [0.766-0.869] as compared to other seven equations. Although the mean bias of the results is quite acceptable, the variability observed in the 95%CI makes not recommend the general use of a spot as a substitute of the 24-hour urine in order to estimate the total urine excretion of Na in a single subject basis.