Sodium Excretion Research Articles

Effect of desmopressin on water and solute circadian rhythms in treatment-naïve children with monosymptomatic enuresis and nocturnal polyuria.

Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors. Solute handling and osmotic excretion have been studied in refractory patients. Nevertheless, data on the effect of desmopressin on these factors are sparse. We conducted a post hoc analysis of the SLEEP study. We analyzed the circadian rhythm of solute and water excretion before and after desmopressin in 30 children with monosymptomatic enuresis and nocturnal diuresis > 100% of expected bladder capacity by means of a 24-h urine concentration profile (four daytime and four nighttime urine portions at equivalent time intervals). Under desmopressin, nocturnal diuresis (rate) and Na/creatinine ratio were significantly lower compared to day values (p = 0.009, p = 0.021, respectively). Osmolality, Na/creatinine, and osmotic excretion showed a significant day vs. night variance only after desmopressin. Nighttime osmotic and sodium excretion were significantly lower (p = 0.004, p = 0.019, respectively) under treatment, indicating the impact of desmopressin on kidney sodium handling. During desmopressin treatment, nocturnal diuresis (rate) showed strong positive correlation with nighttime Na/creatinine (r = 0.436, p < 0.05) and very strongly with nighttime osmotic excretion (r = 0.875, p < 0.0001). However, no correlation was observed with osmolality under desmopressin treatment. The anti-enuretic and antidiuretic effects of desmopressin therapy are not only related to urinary concentration and nocturnal diuresis but also to the amelioration of circadian rhythms of sodium and solute handling.

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.

Psidium guajava leaves extract alters colonic microbiome composition and reduces intestinal sodium absorption in rats exposed to a high-sodium diet.

High sodium intake is a major risk factor for hypertension and renal diseases. Previous studies have shown that a suspension of ethanolic extract of Psidium guajava (guava) leaves (PsE) has antihypertensive effects in rats on a high-sodium diet (HSD), but some mechanisms to that remain unexplored. This study explored whether oral PsE treatment affects sodium handling by the intestine and alters the gut microbiome in HSD-fed rats. Male Wistar rats were divided into two groups: standard salt diet (SSD) and HSD (0.9% Na+), from weaning. After 12 weeks, both groups received PsE (200mg/kg) or a vehicle for an additional 4 weeks. Sodium excretion was measured using flame photometry, and sodium absorption was assessed by intestinal perfusion technique. The gut microbiome was analysed through 16S ribosomal gene sequencing. HSD increased faecal sodium, further elevated by PsE, which inhibited intestinal sodium absorption in HSD rats. HSD altered the abundance of specific bacterial families, which PsE partially reversed. No changes in alpha diversity were noted among groups. These findings suggest that PsE inhibited intestinal sodium handling and that PsE, combined with increased faecal sodium, may reshape the gut microbiome of HSD rats to resemble that of SSD rats.

Glucosuria as a major mechanism-associated effect of sodium-glucose cotransporter 2 inhibitors: Is there cause for concern?

Introduction. One of the main mechanisms of action of SGLT2 inhibitors is an increase in renal excretion of glucose and sodium, development of glucosuria against the background of decreased levels of daily glycemia. The frequency of glucosuria development in patients without DM/prediabetes, receiving SGLT2 inhibitors for the treatment of CHD or CKD, as a consequence of the mechanism of action of SGLT2 inhibitors inhibitors is poorly studied and seems to be very interesting.Aim. To evaluate in real clinical practice the frequency of the development and severity of glucosuria in patients with CHF treated with inhibitors of SGLT2 inhibitors both on the background of concomitant DM2 and without type 2 DM.Materials and methods. Within the framework of a one-stage, prospective, observational study we evaluated the frequency of development and severity of glucosuria in patients with CHF, receiving SGLT2 inhibitors inhibitors, who were in the cardiology department of V.P. Demikhov State Clinical Hospital of Moscow. A total of 230 patients were included in the analysis.Results. The mean age of the patients was 74 [66; 83] years. Median LVEF was 36 [29; 44] %, NTproBNP 1019 [423; 2355] pg/ml. Heart failure with reduced ejection fraction (HFrEF) was recorded in 64.81% of patients, 17.13% had HF with mildly reduced ejection fraction and 18.06% had a СHF preserved ejection fraction. DM2 was present in 38.7 percent of patients with СHF. Among patients with CHF, the ‘glucosuria phenomenon’ due to the administration of SGLT2 inhibitors was observed in 31.16% of those without DM2, and in 52.27% of СHF patients with concomitant DM2.Conclusion. In patients with CHF receiving SGLT2 inhibitors therapy, the ‘glucosuria phenomenon’ developed in one in three patients without overt carbohydrate metabolism abnormalities and one in two with DM2. The findings suggest that the glucosuria effect of SGLT2 inhibitors is not a required event even in patients with DM2, which may influence the incidence of adverse events in general clinical practice. And the cardioprotective benefits of SGLT2 inhibitors may be due to other mechanisms unrelated to glucose excretion, which, according to recent studies, is considered a surrogate predictor of favorable prognosis concerning CHF and renal outcomes. Nevertheless, additional clinical and experimental studies are required to determine the cardioprotective mechanisms of SGLT2 inhibitors and the predictive value of drug-induced glucosuria.

Long-term Outcome of a Chihuahua With Idiopathic Syndrome of Inappropriate Antidiuretic Hormone Secretion.

An approximately 3 yr old female Chihuahua was presented for evaluation of polyuria and polydipsia noted by the owner after adoption. Serum biochemistry and urinalysis revealed hyponatremia, hypochloremia, hypo-osmolality, and normal fractional excretion of sodium. Serum antidiuretic hormone concentration was 5.54 pg/mL and serum copeptin concentration was 135.40 pg/mL. The antidiuretic hormone value was above the reported range for healthy dogs and was considered inappropriate in light of serum osmolality. Idiopathic syndrome of inappropriate antidiuretic hormone secretion was considered the most likely diagnosis after excluding other potential causes, such as diuretic use, renal disease, adrenal disease, and thyroid dysfunction. The dog remains clinically well 2 yr after diagnosis without specific treatment other than minimal dietary salt supplementation. This case is unique because of the absence of systemic or neurologic signs, good long-term outcome without treatment, and use of novel diagnostic testing.

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.

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

Independent and joint associations of urinary potassium excretion with cardiovascular death: a national population-based cohort study

Abstract Background Elevated potassium excretion is associated with lower blood pressure, as well as reduced risks of cardiovascular disease (CVD) death. However, the impact of varied sodium levels on this association remains a topic of debate, and the mediators of this association besides blood pressure remain uncertain. Purpose To examine the joint association of potassium and sodium with CVD mortality risk, and to identify potential mediating factors of this association. Methods Based on the ChinaHEART (China Health Evaluation And risk Reduction through nationwide Teamwork) project, participants aged 35-75 from 239 sites across all 31 provinces in the mainland of China were recruited from November 2014 to December 2022. We collected spot urine samples from participants and estimated 24-hour sodium and potassium excretion using the Kawasaki formula. Death records were captured through data linkage with the National Mortality Surveillance System and Vital Registration. Multiple regressions were used to analyze the association between potassium excretion and CVD death, as well as to examine the addictive interaction of potassium and sodium. Results This study included 270,991 participants with a mean age of 55.8±9.8 years, and 60.5% of them were female. The mean potassium excretion was 54.36±12.58 mmol/d , which was higher in males and people living in the north. Findings revealed a positive correlation between low urinary potassium levels and CVD death , and the lowest adjusted hazard rate for CVD mortality was 0.65 (95% CI: 0.58-0.73) in the group with the highest potassium excretion (i.e. ≥64.27 mmol/d) compared with the reference group (&amp;lt;43.79 mmol/d), after adjusting for sociodemographic characteristics, medical histories, and lifestyles. Age modified the association between potassium excretion and risk of CVD death (P for interaction=0.031). In addition to systolic blood pressure (16.6%), heart rate (2.2%) also served as the significant mediator between urinary potassium excretion and CVD death. The relative excess risk of interaction (RERI) of lower potassium excretion and lower sodium was significantly positive (RERI=0.22, 95% CI: 0.02-0.42), which implied the synergy effect. Conclusion Potassium intake in the Chinese population is evidently lower than the guideline recommendations, and increasing potassium intake, especially in the population aged &amp;lt;65 years, may reduce the risk and burden of cardiovascular and other diseases. Moreover, when sodium intake is insufficient, supplementation with both sodium and potassium salt can achieve greater health benefits.Graphic abstract

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

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.

Sex differences in the adrenal circadian clock: A role for BMAL1 in the regulation of urinary aldosterone excretion and renal electrolyte balance in mice.

Brain and muscle ARNT-Like 1 (BMAL1) is a circadian clock transcription factor that regulates physiological functions. Male adrenal-specific Bmal1 (ASCre/+::Bmal1) KO mice displayed blunted serum corticosterone rhythms, altered blood pressure rhythm, and altered timing of eating, but there is a lack of knowledge in females. This study investigates the role of adrenal BMAL1 in renal electrolyte handling and urinary aldosterone levels in response to low salt in male and female mice. Mice were placed in metabolic cages to measure 12-hour urinary aldosterone after a standard diet and 7 days low salt diet, as well as daily body weight, 12-hour food and water intake, and renal sodium and potassium balance. Adrenal glands and kidneys were collected at ZT0 or ZT12 to measure expression of aldosterone synthesis genes and clock genes. Compared to littermate controls, ASCre/+::Bmal1 KO male and female mice displayed increased urinary aldosterone in response to a low salt diet, although mRNA expression of aldosterone synthesis genes was decreased. Timing of food intake was altered in ASCre/+::Bmal1 KO male and female mice, with a blunted night/day ratio. ASCre/+::Bmal1 KO female mice displayed decreases in renal sodium excretion in response to low salt, but both male and female KO mice had changes in sodium balance that were time-of-day-dependent. In addition, sex differences were found in adrenal and kidney clock gene expression. Notably, this study highlights sex differences in clock gene expression that could contribute to sex differences in physiological functions.

Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney.

The renal epithelial sodium channel (ENaC) is essential for sodium balance and blood pressure control. ENaC undergoes complex proteolytic activation by not yet clearly identified tubular proteases. Here, we examined a potential role of transmembrane serine protease 2 (TMPRSS2). Murine ENaC and TMPRSS2 were (co-)expressed in Xenopus laevis oocytes. ENaC cleavage and function were studied in TMPRSS2-deficient murine cortical collecting duct (mCCDcl1) cells and TMPRSS2-knockout (Tmprss2-/-) mice. Short-circuit currents (ISC) were measured to assess ENaC-mediated transepithelial sodium transport of mCCDcl1 cells. The mCCDcl1 cell transcriptome was studied using RNA sequencing. The effect of low-sodium diet with or without high potassium were compared in Tmprss2-/- and wildtype mice using metabolic cages. ENaC-mediated whole-cell currents were recorded from microdissected tubules of Tmprss2-/- and wildtype mice. In oocytes, co-expression of murine TMPRSS2 and ENaC resulted in fully cleaved γ-ENaC and ∼2-fold stimulation of ENaC currents. High baseline expression of TMPRSS2 was detected in mCCDcl1 cells without a stimulatory effect of aldosterone on its function or transcription. TMPRSS2 knockout in mCCDcl1 cells compromised γ-ENaC cleavage and reduced baseline and aldosterone-stimulated ISC which could be rescued by chymotrypsin. A compensatory transcriptional upregulation of other proteases was not observed. Tmprss2-/- mice kept on standard diet exhibited no apparent phenotype, but renal γ-ENaC cleavage was altered. In response to a low-salt diet, particularly with high potassium intake, Tmprss2-/- mice increased plasma aldosterone significantly more than wildtype mice to achieve a similar reduction of renal sodium excretion. Importantly, the stimulatory effect of trypsin on renal tubular ENaC currents was much more pronounced in Tmprss2-/- mice than that in wildtype mice. This indicated the presence of incompletely cleaved and less active channels at the cell surface of TMPRSS2-deficient tubular epithelial cells. TMPRSS2 contributes to proteolytic ENaC activation in mouse kidney in vivo.

Urine chloride trajectory and relationship with diuretic response in acute heart failure.

Sodium excretion is a well-defined marker used to assess diuretic response in acute heart failure (AHF). Despite a strong pathophysiological background, the role of urine chloride excretion has not been described and established yet. We aimed to evaluate chloride trajectory during intensive diuretic treatment in AHF patients and examine its potential role in predicting poor diuretic response. The study was conducted on 50 AHF patients. Participants were included within the first 36h of hospitalization. They received furosemide dose adjusted for body weight (half in bolus, half in 2h infusion). Post-diuretic hourly urine collection with biochemical analysis was performed. In general, the concentrations of urine chloride (uCl-) and sodium (uNa+) at the baseline samples exhibited a comparable level (71±39 vs. 70±44mmol/L, respectively; P=0.99), but across all post-furosemide study timepoints, uCl- remained significantly higher than uNa+ since 1 to 6h of the study. In this course, both ions (uCl- and uNa+) reached peak values in 2h (114±28 vs. 97±34mmol/L, respectively; P<0.01). The pattern of uCl- dominance over uNa+ concentration was also observed in separate analyses of patients naïve to furosemide and those chronically exposed to furosemide. Regardless of these patterns, naïve to furosemide individuals excreted more ions (both uCl- and uNa+) than chronically exposed patients at all timepoints. Additionally, a strong, linear correlation between uCl- and uNa+ was observed in each post-furosemide timepoint (the strongest in 1h r=0.87; P<0.001). Both interdependent ions concentration was almost parallel when analysed in chronic furosemide users and those naïve to furosemide separately [uCl-=0.85*uNa++28.82, P<0.001, R2=0.83 for chronic furosemide users, and uCl-=0.72*uNa++41.55, P<0.001, R2=0.65 for naïves to furosemide (linear regression model)]. Moreover, uCl- (with cutoff point: 72mmol/L) was a satisfactory predictive factor for poor diuretic response (<100mL/h in 6h since the beginning of furosemide infusion) [odds ratio (OR) 95% confidence interval (CI): 39.0 (3.8-405.00)]. It presented those properties also after adjusting for urine creatinine [cutoff point: 0.296mmol/mg-OR (95% CI): 81.0 (8.0-816.0)]. Urine chloride and sodium are highly interrelated during decongestion of AHF patients. The uCl- (cutoff 72mmol/L) exhibits better prognostic abilities to identify poor diuretic response than uNa+.

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.

Involvement of Cholinergic and Cyclooxygenase Pathways in the Diuretic Effects of Rosmarinic Acid.

Rosmarinic acid (RA) is a natural antioxidant known for its diverse biological activities. Although its diuretic activity has been previously established, the mode of action remained unclear. To investigate this, we examined the diuretic activity of RA alone and in combination with hydrochlorothiazide (HCTZ), amiloride (AML), atropine (ATR), and indomethacin (INDO) to see if any of these drugs could interfere with RA's activity in an 8-hour acute diuresis animal model. We observed that RA increases urine excretion and may have a synergistic effect in the HCTZ+RA group, with a potassium-sparing capacity. In the AML+RA group, we also noted increased urine excretion while sodium and potassium excretion decreased. ATR and INDO prevented RA from increasing urine excretion, suggesting a potential interaction with muscarinic receptors or a role in promoting prostaglandin production. Additionally, molecular docking analysis indicated possible interactions with key receptors involved in increased diuresis or free-electrolyte water excretion.

Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

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.

6411 Ozempic - Oh no! Acute Renal Failure Associated with Initiation of Semaglutide

Abstract Disclosure: K. Barney: None. D. Tahir: None. A. Pannu: None. R. Saeed: None. Background: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which has been proven to reduce weight in those with obesity and improve glycemic control in patients with type II diabetes mellitus. The effect of semaglutide on kidney function has not been well established. The phase 3b SUSTAIN trials revealed that when compared with other GLP-1 agonists, semaglutide exhibited more frequent acute kidney injuries [1-3]. The SUSTAIN 6 trial reported two instances of acute renal failure (ARF) in patients with chronic kidney disease, and one case of ARF in a patient with normal kidney function who was treated with semaglutide [3]. Despite these reports, the SUSTAIN 1-9 trials report no significant decline in kidney function associated with semaglutide [3-6]. Case: We present the case of a 58-year-old male with a past medical history of human immunodeficiency virus (HIV), type II diabetes mellitus, and hypertension who presented to the hospital with ARF after initiation of Ozempic (semaglutide) two months prior to presentation. On admission, vitals were stable and physical examination was benign. His pertinent labs were blood urea nitrogen (BUN) 55 mg/dL, creatinine 5.94 mg/dL (baseline 1.2 mg/dL), and urinalysis with 2+ protein. To determine the cause of his renal failure, urine sodium and creatinine were obtained to calculate his fractional excretion of sodium, which was found to be consistent with intrinsic renal disease. Further workup, including renal ultrasound, urine protein, urine eosinophils, complement and free light chain levels, and creatinine kinase, were unrevealing for cause of intrinsic renal injury. He was managed with intravenous fluids and his creatinine improved to 2.03 mg/dL. Given the acute onset of the patient’s renal failure and recent initiation of Ozempic, it was determined that this medication was the cause of his renal failure, and it was discontinued on discharge. He has since followed up with nephrology and endocrinology. He remains off Ozempic and is doing well. Conclusions: Our case highlights a rare but significant adverse effect of semaglutide on renal function. As the use of semaglutide has increased due to its rising popularity for weight loss and glycemic control in type II diabetes mellitus, the potential for renal injury should be considered and discussed with patients. Furthermore, it is imperative that semaglutide associated renal injury be considered as a cause for ARF in patients taking this medication. This case demonstrates that instances of ARF associated with semaglutide treatment are a cause for concern and further exploration. Presentation: 6/1/2024