Urinary Sodium Excretion Research Articles

Long-term excessive salt consumption alters villous and crypt morphology and the protein expression of uroguanylin, TRPV6 and PMCA1b in the rat small intestine.

Although long-term high dietary sodium consumption often aggravates hypertension and bone loss, sodium in the intestinal lumen has been known to promote absorption of nutrients and other ions, e.g., glucose and calcium. However, whether high-salt diet (HSD) altered mucosal morphology, villous cell turnover and calcium transporter expression remained elusive. Herein, rats were treated with HSD containing 8% wt/wt NaCl for up to 5 months. HSD rats exhibited a marked increase in sodium intake with high fecal and urinary sodium excretion, as compared to the control group treated with normal diet. Intestinal histomorphometry revealed increasing of crypt depth and villous height in 3- and 4-month HSD groups, respectively, consistent with larger mucosal-to-serosal amplification ratio that reflected an increased surface area for nutrient absorption. The signals of Ki-67-positive cells was enhanced in the crypts as visualized by multiphoton fluorescence microscopy, whereas the TUNEL-positive cells were decreased in the villi of HSD, suggesting greater crypt cell proliferation and a reduction of villous cell apoptosis. Confocal microscopy showed higher expression of TRPV6 protein in the villous tip of HSD, while PMCA1 expression was increased in villous tip and crypt areas. The percentage of cells with highly expressed uroguanylin-an endogenous intestinal natriuretic peptide-was significantly higher in HSD group. In conclusion, HSD profoundly changed the intestinal morphology and turnover of epithelial cell, increased the expression of calcium transporters and uroguanylin. Our findings reflect pathophysiological adaptations in the intestine, which might be another target organ for drug discovery against HSD-induced osteopathy in the future.

Association Between Sodium- and Potassium-Related Urinary Markers and the Prevalence of Atrial Fibrillation.

The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence. Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1-Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07-1.73) and 1.59 (95% CI 1.20-2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence. AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.

Diuretics in patients with chronic kidney disease.

Diuretic drugs act on electrolyte transporters in the kidney to induce diuresis and are often used in chronic kidney disease (CKD), given that nephron loss creates a deficit in the ability to excrete dietary sodium, which promotes an increase in plasma volume. This rise in plasma volume is exacerbated by CKD-induced systemic and intra-renal activation of the renin-angiotensin-aldosterone-system, which further limits urinary sodium excretion. In the absence of a compensatory decrease in systemic vascular resistance, increases in plasma volume induced by sodium retention can manifest as a rise in systemic arterial blood pressure. Management of sodium and volume overload in patients with CKD is therefore typically based on restriction of dietary sodium intake and the use of diuretic agents to enhance urinary sodium excretion. Thiazide and thiazide-type diuretics are foundational therapies for the management of hypertension, whereas loop diuretics are often needed for volume overload, which might also require combination therapies. Mineralocorticoid receptor antagonists have an important role in the management of diuretic-resistant volume overload or treatment-resistant hypertension. Additionally, diuretics can be used for the diagnosis of kidney diseases and in the management of hyperkalaemia or hypokalaemia, hyponatraemia, hypercalcaemia and hypomagnesaemia.

Three-month Mortality Outcomes Of Patients With Acute Heart Failure According To Urinary Sodium Excretion

Three-month Mortality Outcomes Of Patients With Acute Heart Failure According To Urinary Sodium Excretion

Trajectory of Urine Parameters by Adding Herbal Kampo Medicine Goreisan to Tolvaptan in Patients with Congestive Heart Failure.

Background: Even in current guideline-directed medical therapy, including recently introduced vasopressin type 2 receptor antagonist tolvaptan, congestion has not been resolved in patients with heart failure. Kampo medicine goreisan has been receiving considerable attention as an additional therapy for patients who are refractory to conventional diuretics therapy, including tolvaptan. However, the impact of goreisan on urine electrolytes remains uncertain. Methods: Patients with congestive heart failure who received goreisan as an add-on therapy to tolvaptan-incorporated medical therapy were prospectively included. The changes in urine parameters during the first 24 h were assessed as a primary concern. Baseline factors associated with an increase in urine sodium excretion were investigated. Results: A total of 21 patients were included. The median age was 81 (77, 86), and 13 (62%) were men. Twenty-four hours after the initiation of goreisan, urine osmolality decreased significantly, urine sodium level remained unchanged, urine potassium and glucose levels decreased significantly, urine urea nitrogen level tended to decrease, and urine volume tended to increase. The fractional excretion of sodium tended to increase. Baseline plasma B-type natriuretic peptide level had a positive correlation with a change in fractional excretion of sodium from baseline to day 1 (r = 0.52, p = 0.015). Conclusions: Goreisan may increase urine volume via aquaretic and natriuretic effects in patients with congestive heart failure receiving tolvaptan-incorporated medical therapy. Goreisan may have the ability to "modulate" fluid balance depending on congestion status.

Effects of Cacna1d D307G mutation on blood pressure and kidney function in rats with salt loading.

Our recent findings revealed that CACNA1D D307G mutation participates in the early onset hypertension. we used CRISPR/Cas9 technique to generate the Cacna1d D307G mutation rat model and investigated the effects of Cacna1d D307G mutation on blood pressure (BP) and renal function. Rats fed normal-salt diet (NSD) had normal plasma aldosterone levels but higher plasma ET-1 and mildly elevated systolic blood pressure (SBP) in D307G and G307G rats compared with the wild type (WT) until 24 weeks. Renal function and renal histopathology did not significantly differ among the three groups. When fed high-salt diet (HSD), D307G and G307G rats showed more sensitivity to HSD. The results showed a further increase in SBP than in WT rats. Plasma and vascular ET-1 level and cortex and renal artery endothelin type A receptor (ETA) protein expression were significantly increased. Enhanced renal injury was also noted as indicated by an increased ratio of kidney weight/body weight, elevated urinary protein and albumin/creatinine ratio, higher kidney injury molecule-1 (KIM-1) levels, advanced fibrosis and apoptosis, and inflammation. Further experiments revealed a reduction in urinary sodium excretion and creatinine clearance. Higher protein expression of renal cortex epithelial sodium channel α subunit (αENaC) was confirmed in D307G and G307G rats fed HSD. However, a selective ETA receptor blockade (ABT-627) could partially reverse the increased SBP, increased serum KIM-1 level, upregulated renal cortex protein expression of αENaC, and reduced urinary sodium excretion with reduced creatinine clearance in D307G rats fed HSD. Activation of ET-1/ETA system in D307G mutation rats might contributed to increased sensitivity to salt loading, augmented hypertension, and exacerbated the renal injury.

Long-Term Effects of a Comprehensive Intervention Strategy for Salt Reduction in China: Scale-Up of a Cluster Randomized Controlled Trial.

Salt intake in China was high and a series of salt reduction measures were accordingly carried out recently. Our study aimed to assess the long-term effect of a scale-up community randomized controlled trial (RCT); Methods: Individuals between the ages of 18 and 75, from six provinces in China, were recruited and randomized into control (n = 1347) and intervention (n = 1346) groups. A one-year salt reduction intervention was first implemented in the intervention group, followed by a two-year scale-up intervention in both groups. The 24 h urine sample, anthropometric measurement, and knowledge, attitude, and practice (KAP) of salt reduction, as well as lifestyle information, were collected at baseline, after one-year RCT (mid-term evaluation, n = 2456), and two-year scale-up intervention (terminal evaluation, n = 2267); Results: Both control (351.82 mg/24 h, p < 0.001) and intervention (192.84 mg/24 h, p = 0.006) groups showed a decrease in 24 h urinary sodium excretion from baseline to terminal evaluation. Except for an increase in 24 h urinary potassium excretion (85.03 mg/24 h, p = 0.004) and a decrease in systolic blood pressure (SBP) (2.95 mm Hg, p < 0.001) in the intervention group at the mid-term assessment, no statistically significant differences in other indicators were found between two groups. The KAP of salt reduction in two groups was gradually improved; Conclusions: After one-year RCT and two-year scale-up, all participants showed a decreasing trend in 24 h urinary sodium excretion and an increase in salt reduction KAP. The community salt reduction intervention package has the potential for broader application across other regions in China.

Knowledge, Attitudes, and Behaviors Toward Salt Consumption and Its Association With 24-Hour Urinary Sodium and Potassium Excretion in Adults Living in Mexico City: Cross-Sectional Study.

The World Health Organization recommends a daily sodium intake of less than 2000 mg for adults; however, the Mexican population, like many others globally, consumes more sodium than this recommended amount. Excessive sodium intake is often accompanied by inadequate potassium intake. The association between knowledge, attitudes, and behaviors (KAB) and actual sodium intake has yielded mixed results across various populations. In Mexico, however, salt/sodium-related KAB and its relationship with sodium and potassium intake have not been evaluated. This study primarily aims to describe salt/sodium-related KAB in a Mexican population and, secondarily, to explore the association between KAB and 24-hour urinary sodium and potassium excretion. We conducted a cross-sectional study in an adult population from Mexico City and the surrounding metropolitan area. Self-reported KAB related to salt/sodium intake was assessed using a survey developed by the Pan American Health Organization. Anthropometric measurements were taken, and 24-hour urinary sodium and potassium excretion levels were determined. Descriptive statistics were stratified by sex and presented as means (SD) or median (25th-75th percentiles) for continuous variables, and as absolute and relative frequencies for categorical variables. The associations between KAB and sodium and potassium excretion were assessed using analysis of covariance, adjusting for age, sex, BMI, and daily energy intake as covariates, with the Šidák correction applied for multiple comparisons. Overall, 232 participants were recruited (women, n=184, 79.3%). The mean urinary sodium and potassium excretion were estimated to be 2582.5 and 1493.5 mg/day, respectively. A higher proportion of men did not know the amount of sodium they consumed compared with women (12/48, 25%, vs 15/184, 8.2%, P=.01). More women reported knowing that there is a recommended amount for daily sodium intake than men (46/184, 25%, vs 10/48, 20.8%, P=.02). Additionally, more than half of men (30/48, 62.5%) reported never or rarely reading food labels, compared with women (96/184, 52.1%, P=.04). Better salt/sodium-related KAB was associated with higher adjusted mean sodium and potassium excretion. For example, mean sodium excretion was 3011.5 (95% CI 2640.1-3382.9) mg/day among participants who reported knowing the difference between salt and sodium, compared with 2592.8 (95% CI 2417.2-2768.3) mg/day in those who reported not knowing this difference (P=.049). Similarly, potassium excretion was 1864.9 (95% CI 1669.6-2060.3) mg/day for those who knew the difference, compared with 1512.5 (95% CI 1420.1-1604.8) mg/day for those who did not (P=.002). Additionally, higher urinary sodium excretion was observed among participants who reported consuming too much sodium (3216.0 mg/day, 95% CI 2867.1-3565.0 mg/day) compared with those who claimed to eat just the right amount (2584.3 mg/day, 95% CI 2384.9-2783.7 mg/day, P=.01). Salt/sodium-related KAB was poor in this study sample. Moreover, KAB had a greater impact on potassium excretion than on sodium excretion, highlighting the need for more strategies to improve KAB related to salt/sodium intake. Additionally, it is important to consider other strategies aimed at modifying the sodium content of foods.

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, &amp;gt;2500-4000, &amp;gt;4000 g; &amp;lt;2.3, 2.3-4.6 and &amp;gt;4.6 g; and &amp;lt;1, 1-2 , &amp;gt;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&amp;lt;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&amp;lt;0.01), and at T2 (0.34±0.66; p&amp;lt;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&amp;lt;0.001), and at T2 (13±11; p&amp;lt;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&amp;lt;0.05). We divided patients into two groups: "responders" (with ≥15 reduction of B-lines between T0 and T2) and "non-responders" (with &amp;lt;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-h 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 towards 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 knowledge, attitude and practice questionnaire, sodium and potassium excretions and food records were taken. The UAE. A sample of 190 healthy individuals aged between 20 and 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/d and 2533·3 ± 615 mg/d, respectively. The means were significantly different compared with the 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 knowledge, attitude and practice 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 emphasise the need to establish education and public awareness programmes 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.

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.

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 < 0.001, respectively). Urinary amylase-to-creatinine ratio, total iron-binding capacity, and antithrombin were the variables most strongly associated with disease severity (p < 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.

Practical use and target value of urine sodium-to-potassium ratio in assessment of hypertension risk for Japanese: Consensus Statement by the Japanese Society of Hypertension Working Group on Urine Sodium-to-Potassium Ratio.

Epidemiological studies have demonstrated that the urine sodium-to-potassium (Na/K) ratio is more positively associated with high blood pressure and cardiovascular disease risk than either urine sodium or potassium excretion alone. In this consensus statement, we recommend using the average Na/K ratio of casual urines randomly taken in various times on at least four days a week for a reliable individual estimate because of high day-to-day and intraday variability of casual urine Na/K ratio within individuals. Although a continuous positive association exists between the Na/K ratio and high blood pressure or cardiovascular disease risk, for clinical and public health decision making for Japanese, we recommend using an average urine Na/K ratio of 2 as an optimal target value because this aligns with recommendations for both sodium and potassium intake in the Dietary Reference Intakes for Japanese, 2020, considering a typical Japanese dietary pattern. We also suggest that an average urine Na/K ratio of 4 is a feasible target value to achieve a temporary goal of being below the mean values of the urine Na/K ratio across Japanese general populations. These recommendations apply mainly for apparently healthy individuals, but not for patients with specific conditions due to the lack of supporting data. Current evidence for the usefulness of measuring the urine Na/K ratio for the prevention or control of hypertension remains inconclusive and warrants further investigation.

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.