Urinary Electrolyte Excretion Research Articles

The endocrine basis of the cardio-renal axis: New perspectives regarding corin.

The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans-membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman etal. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss-of-function variant of the gene encoding corin (Cor-/-). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac-derived ANP in these patients, as implied by Feldman etal. Yet, in this mini-review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na+ and water exertion. Collectively, it seems that beside the classic well-established cardio-renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis.

Diclofenac is the non-steroidal anti-inflammatory drug (NSAID) mostly prescribed worldwide, but it is highly associated with hypertension and acute kidney injury. Despite that, little information is available about the renal effects of diclofenac in hypertensive individuals, which led us to carry out this comparative study between the renal effects of this NSAID in normotensive (NTR) and spontaneously hypertensive rats (SHR). Male Wistar NTR and SHR were orally treated with vehicle (V: 10 mL/kg) or diclofenac sodium (D: 100 mg/kg) once a day for 3 days. Urine volume, electrolytes excretion (Na+, K+, Cl-, and Ca2+), urea, creatinine, pH, and osmolarity were evaluated. Furthermore, blood samples and renal tissue were collected to perform biochemical and histological analysis. Diclofenac increased the renal corpuscle and bowman's space in the SHR, while no microscopic changes were observed in the renal tissue of NTR. Regarding the urinary parameters, diclofenac reduced urine volume, pH, osmolarity, and all electrolytes excretion, followed by decreased urea and creatinine levels in both lineages. Moreover, it also induced hyponatremia, hypokalemia, and hypocalcemia in SHR, while reduced glutathione-S-transferase activity, lipid hydroperoxides, and nitrite levels in renal tissue. The data presented herein demonstrated that diclofenac induces renal damage and impaired renal function in both NTR and SHR, but those effects are exacerbated in SHR, as seen by the histological changes and electrolytes balance disturbance, therefore, reinforcing that diclofenac may increase the risks of cardiovascular events in hypertensive patients.

Estimation of 24-hour urinary sodium and potassium excretion among Chinese adults: a cross-sectional study from the China National Nutrition Survey

BackgroundHigh-sodium intake is one of the most important risk factors for hypertension and cardiovascular disease, yet reliable national estimates of sodium intake in Chinese adults have not been reported. ObjectivesWe estimated 24-h urinary sodium and potassium excretion and population daily sodium and potassium intake of Chinese adults for the first time at a national level. MethodsA nationally representative cross-sectional survey was conducted to collect 24-h urine specimens from Chinese adults aged ≥18 y as part of the China National Nutrition Survey 2015. Finally, 10,114 participants (4932 males and 5182 females) with complete 24-h urine specimens were included in the analysis. Estimates of mean urinary electrolyte excretion and demographic, socioeconomic, and health characteristics were used with weighted coefficients that accounted for sample selection probabilities, poststratification weighting, and nonresponse rates. ResultsThe estimation of overall weighted mean 24-h urinary sodium excretion was 4121 mg (95% confidence interval [CI]: 3993, 4250), 4155 mg (95% CI: 3993, 4317) in males and 4081 mg (95% CI: 3953, 4209) in females (P for sex difference = 0.36). Overall mean 24-h urinary potassium excretion was 1534 mg (95% CI: 1492, 1577), 1468 mg (95% CI: 1424, 1513) in males and 1614 mg (95% CI: 1569–1660) in females (P for sex difference <0.001). Mean 24-h urinary sodium excretion was significantly higher in rural adults (4350 mg; 95% CI: 4217, 4483) than in urban residents (3909 mg; 95% CI: 3739, 4080; P < 0.001), and in northern residents (4388 mg; 95% CI: 4237, 4539) than in southern residents (3998 mg; 95% CI: 3832, 4163; P = 0.002). ConclusionsThe first nationwide survey with 24-h urine collection confirmed that mean sodium intake in Chinese adults was more than twice the upper limit, whereas mean potassium intake was <60% of the lower limit, recommended by the World Health Organization. Urgent measures should be taken to reduce sodium intake and increase potassium intake in China.

Trimethoprim inhibits renal H+-K+-ATPase in states of K+ depletion.

There is growing consensus that under physiological conditions, collecting duct H+ secretion is independent of epithelial Na+ channel (ENaC) activity. We have recently shown that the direct ENaC inhibitor benzamil acutely impairs H+ excretion by blocking renal H+-K+-ATPase. However, the question remains whether inhibition of ENaC per se causes alterations in renal H+ excretion. To revisit this question, we studied the effect of the antibiotic trimethoprim (TMP), which is well known to cause K+ retention by direct ENaC inhibition. The acute effect of TMP (5 µg/g body wt) was assessed in bladder-catheterized mice, allowing real-time measurement of urinary pH, electrolyte, and acid excretion. Dietary K+ depletion was used to increase renal H+-K+-ATPase activity. In addition, the effect of TMP was investigated in vitro using pig gastric H+-K+-ATPase-enriched membrane vesicles. TMP acutely increased natriuresis and decreased kaliuresis, confirming its ENaC-inhibiting property. Under control diet conditions, TMP had no effect on urinary pH or acid excretion. Interestingly, K+ depletion unmasked an acute urine alkalizing effect of TMP. This finding was corroborated by in vitro experiments showing that TMP inhibits H+-K+-ATPase activity, albeit at much higher concentrations than benzamil. In conclusion, under control diet conditions, TMP inhibited ENaC function without changing urinary H+ excretion. This finding further supports the hypothesis that the inhibition of ENaC per se does not impair H+ excretion in the collecting duct. Moreover, TMP-induced urinary alkalization in animals fed a low-K+ diet highlights the importance of renal H+-K+-ATPase-mediated H+ secretion in states of K+ depletion.NEW & NOTEWORTHY The antibiotic trimethoprim (TMP) often mediates K+ retention and metabolic acidosis. We suggest a revision of the underlying mechanism that causes metabolic acidosis. Our results indicate that TMP-induced metabolic acidosis is secondary to epithelial Na+ channel-dependent K+ retention. Under control dietary conditions, TMP does not per se inhibit collecting duct H+ secretion. These findings add further argument against a physiologically relevant voltage-dependent mechanism of collecting duct H+ excretion.

Abstract P376: Collecting Duct Renin And Its Receptor Contributes To Unilateral Ureteral Obstruction-induced Kidney Injury Via Activation Of The Intrarenal Ras

The collecting duct (CD) is well known for its role in fine-tuning urinary excretion of electrolytes and water. Emerging evidence suggests a potential role played by the CD in immunity and renal injury but the underlying mechanism largely remains elusive. Within the CD, (pro)renin receptor (PRR) via site-1 protease (S1P)-derived soluble PRR interacts with renin controls the intrarenal renin-angiotensin system (RAS) to regulate Na+ and water balance and blood pressure. The present study attempted to employ mouse models of CD-specific deletion of PRR and renin (CD PRR KO and CD renin KO, respectively) and a specific S1P inhibitor PF-429242 (PF) to explore the pathogenic role of this local system in renal injury induced by unilateral ureteral obstruction (UUO). Male 3-4-month-old CD PRR KO and CD renin KO, and their respective floxed controls were subjected to UUO surgery or sham operation for 3 days, followed by analysis of renal fibrosis, inflammation, and indices of the intrarenal RAS. Male 3-4-month-old C57BL/6 mice were subjected to the same surgical procedures and infused with vehicle or PF at 20 mg/kg/day via minipump for 3 days, followed by analysis of the same parameters. 3-day UUO in floxed mice induced renal abundance of fibronectin and α-SMA by 8.6 folds and 5.8 folds, respectively, as assessed by immunoblotting analysis. qRT-PCR detected similar magnitude of increases in mRNA expression of fibronectin, α-SMA, as well as collagen III, collagen I, and TGF-β in the obstructed kidneys. Similar results were obtained by Trichrome Masson staining. In parallel, the obstructed kidney exhibited 4-5-fold increases in renal medullary renin mRNA, renin activity, and active renin content contrasting to unaltered renin levels in the renal cortex. CD-specific deletion of PRR and renin induced comparable attenuation of various indices of renal fibrosis, inflammation, renal medullary renin levels so did PF treatment. UUO induced a 2-fold increase in plasma sPRR, which was completely blocked by PF treatment. Taken together, our results demonstrated that CD PRR/sPRR-dependent activation of renin represents a key determinant of the intrarenal RAS and thus obstruction-induced renal inflammation and fibrosis.

Fractional excretion of electrolytes and neutrophil gelatinase-associated lipocalin as early biomarkers of acute kidney injury in dogs with acute pancreatitis.

To determine if fractional excretion of urinary electrolytes and neutrophil gelatinase-associated lipocalin could detect different degrees of kidney injury in dogs with naturally occurring acute pancreatitis. We included dogs with acute pancreatitis. Dogs with a history of kidney disease, urinary tract infection, dogs which received potentially nephrotoxic drugs and dogs managed with haemodialysis were excluded. Acute kidney injury was diagnosed if there was an acute onset of clinical signs, haemato-chemical results compatible with acute kidney injury. Students or staff-owned dogs were selected to build the healthy group. The study population was composed of 53 dogs: acute pancreatitis with AKI (n=15), acute pancreatitis alone (n=23), and healthy dogs (n=15). In dogs with acute pancreatitis and AKI, all the FEs of urine electrolytes were significantly higher than dogs with acute pancreatitis alone and healthy ones. Dogs with acute pancreatitis alone had higher uNGAL/uCr than healthy dogs (median 54 ng/mg vs. 0.1 ng/mg) and lower compared to AP-AKI patients (54 ng/mg vs 209 ng/mg). Some fractional excretion of electrolytes are increased acute kidney injury dogs, however their role in the early detection of renal injury in acute pancreatitis dogs remains doubtful. On the contrary, urinary neutrophil gelatinase-associated lipocalin had higher concentrations in dogs with acute pancreatitis with or without acute kidney injury compared to healthy controls, suggesting that it may be used as an early marker of renal tubular damage in acute pancreatitis dogs.

Normonatremic Transient Renal Salt Wasting (TRSW) Is Not Rare in a Department of Internal Medicine.

We previously reported that for around 5% of patients hospitalized with hyponatremia, it was related to what is called "transient renal salt wasting" (TRSW). In the present study we ask whether TRSW can also be observed in patients without hyponatremia. In this observational retrospective study we analyze the urine solute excretion of 200 consecutive normonatremic patients with normal kidney function and admitted in our department over one year. Patients were selected for analyses of FE.K, UCa/UCr and FE.PO4 if FE.Na was higher than 2% (N &lt; 1.6%) before any treatment, and only if they were not taking diuretics. Eleven normonatremic patients presented with transient high FE.Na &gt; 2% on admission (2.9 ± 0.6% with a high FE.K of 28 ± 6.4%; a high UCa/UCr of 0.37 ± 0.13 and a high FE.PO4 of 23.2 ± 9.6%). All of these patients were elderly. Seven were female and four were male. Neurological disorders were observed in six patients (three strokes, one transient ischemic attack, one syncope and one epileptic attack). Heart problems were observed in three patients (all angina pectoris, two of which also had HBP). One patient presented with rectal bleeding with HBP, and another presented COPD with a pneumothorax. One patient with angina pectoris showed a transient relapse after four days of hospitalization (FE.Na 3.6%). The urine electrolyte excretion in these patients are similar to those observed after furosemide intake. Normonatremic TRSW is not a rare observation, particularly in patients with neurological or cardiac problems.

Effects of Potassium Supplementation and Kir7.1 Knockout on Renal Function During the Progression of Salt‐Sensitive Hypertension

The inward‐rectifying potassium channel (Kir) family has been shown to play an important role in the kidney’s ability to maintain electrolyte homeostasis as well as blood pressure. Kir7.1 (encoded by the Kcnj13 gene) is expressed in the kidney, though its role in renal function is rudimentary. To examine the role of Kir7.1 in renal electrolyte handling and the development of salt‐induced hypertension, we generated a knockout of Kcnj13 on the Dahl salt‐sensitive (SS) rat background. Rats with the knockout of Kcnj13 were embryonically lethal; therefore, to study the Kir7.1 channel, we used heterozygous (SSKcnj13+/‐) rats. Immunohistochemistry staining for Kir7.1 revealed basolateral staining in the cortical sections of the kidneys in wild‐type littermates (WT), while SSKcnj13+/‐ rats showed little to no staining. In addition, immunofluorescence analysis confirmed that Kir7.1 was localized on the basolateral side in tubules and revealed that Kir7.1 co‐localized with aquaporin 2 and sodium‐chloride cotransporter (NCC). This data indicates that Kir7.1 is expressed in the cortical collecting duct (CCD) and the distal convoluted tubule (DCT). SSKcnj13+/‐ rats were further used to measure blood pressure and electrolyte handling changes during the development of salt‐induced hypertension. DSI telemeters were implanted in animals at 8 weeks of age; after a week to recover from surgery, animals were fed a high salt 4% NaCl diet (HS) for three weeks. Both WT and SSKcnj13+/‐rats become hypertensive after three weeks of HS; no difference between mean arterial pressures (153.1 ± 5.7 vs. 159.2 ± 6.9 mmHg for WT and SSKcnj13+/‐rats, respectively) was identified. Serum electrolytes were measured and also showed no difference in the amount of potassium (3.4 ± 0.1 vs. 3.5 ± 0.1 mmol/L) or sodium (142 ± 0.8 vs. 142 ± 0.4 mmol/L). Furthermore, urinary electrolyte excretion was measured and revealed no differences between WT and SSKcnj13+/‐ animals for potassium (14.0 ± 0.6 vs. 15.6 ± 1.9 K+/Cre) or sodium excretion (91 ± 11 vs. 117 ± 16 Na+/Cre). Potassium supplementation has previously been shown to augment renal Kir7.1 expression. Thus, we repeated the previous protocol but instead using a high salt and high potassium 4% NaCl and 2% KCl (HSHK) diet. After three weeks on this diet, animals exhibited no difference in blood pressure (154.2 ± 9.1 vs 145.6 ± 4.1 mmHg) and no differences in plasma potassium (4.0 ± 0.1 vs 4.0 ± 0.1 mmol/L) or sodium (139 ± 1 vs 139 ± 1 mmol/L). Urinary electrolyte excretion showed no differences in potassium excretion (60.9 ± 3.3 vs 54.8 ± 1.1 K+/Cre), but SSKcnj13+/‐ animals did have a significant decrease in sodium excretion (130 ± 8 vs 103 ± 3 Na+/Cre). Altogether, we have confirmed the presence of Kir7.1 in the CCD and DCT, found that heterozygous knockout of Kir7.1 does not affect the development of blood pressure on a HS or HSHK diet. However, we do see a reduction in sodium excretion in SSKcnj13+/‐rats on the HSHK diet, suggesting that Kir7.1’s role may be more pronounced under conditions of higher potassium.

Anti-hypertensive effects of Callisia fragrans extract on Reno-vascular hypertensive rats

ABSTRACT Objectives This study aims to investigate the anti-hypertensive effects of aqueous extract of Callisia fragrans and their underlying mechanism using a two-kidney one-clip (2K1C) model of reno-vascular hypertension in rats. Methods The reno-vascular hypertensive rats were treated with C. fragrans leaf extract (100 and 500 mg/kg; p.o.) and a reference drug, captopril (20 mg/kg; p.o.), for 4 weeks. The blood pressure and heart rate were recorded using a tail-cuff. The heart weight, left ventricular wall thickness, and serum creatinine and urea levels were measured. A spectrophotometric assay was used to analyze the angiotensin-converting enzyme (ACE) inhibition activity of the extract and the reference drug. The total volume and the concentration of sodium, potassium, and chloride in urine samples were evaluated. Results C. fragrans extract significantly reduced both systolic and diastolic blood pressures in the reno-vascular hypertensive rats. No significant difference in the heart rate was observed between each animal group. C. fragrans extract reduced the 2K1C-induced increase in the heart and body weight ratio and the left ventricular wall thickness. Moreover, the extract also attenuated the increase in serum urea induced by the 2K1C treatment. C. fragrans extract inhibited ACE activity in vitro with an IC50 of 20.97 ± 3.94 µg/ml. The urine output and urinary electrolyte excretion significantly increased in C. fragrans extract-treated rats. Conclusions These findings demonstrated that C. fragrans extract can mitigate hypertension and alleviate ventricular hypertrophy and renal dysfunction in reno-vascular hypertensive rats, at least in part via ACE activity inhibition and diuretic property.

Synthesis and Diuretic Activity of Substituted 1,3,4-Thiadiazoles.

1,3,4-Thiadiazole nuclease, a 5-membered heterocyclic ring system containing two nitrogen and one sulfur atoms in addition to carbon atoms, is compound that showed promising results in the process of searching new diuretic agents. In this study, seven 5- and 2-thioate derivatives of 1, 3, 4-thiadiazoles were synthesized by substitution reaction using acetone as solvent and K2CO3 as a base. The compounds ware then characterized by using IR and NMR spectroscopy. The diuretic activity of the compounds was evaluated on Swiss albino mice by measuring urine volume, urinary pH, and urinary Na+, K+, and Cl−. The result showed increase in urinary excretion of both water and electrolytes. 5-Methyl-substituted derivatives of 1, 3, 4-thiadiazoles showed significant increase in excretion of both water and electrolytes when they are compared to both negative control and 5-amino-substituted derivatives. The highest diuretic activity (0.82) was recorded for para-nitro-substituted benzene ring at 2-thioate group of 5-methyl-1, 3, 4-thiadiazole, while the least (0.56) was recorded for propanethioate group at 2nd position and amine group at 5th position of 1, 3, 4-thiadiazole. The finding of the present study showed that all the compounds have diuretic activity and 5-methyl derivatives of 1, 3, 4-thiadiazoles exhibited significant diuretic activity.

Effects of high salinity in drinking water on behaviors, growth, and renal electrolyte excretion in crossbred Boer goats under tropical conditions.

Background and Aim:The high salinity of drinking water has been a significant problem of the Mekong Rivers Delta. Animals drinking high salinity water altered feed and water intake (WI), urinary electrolytes excretion, and productivity. This study aimed to evaluate the effects of high salinity in drinking water on drinking and eating behaviors and kidney function in crossbred goats.Materials and Methods:The experiment was completely randomized with two treatments: freshwater (0%, seawater [SW0]) and water high in salinity (1.5%, SW1.5) from diluted SW, with five replicates (five animals per treatment). This experiment lasted 3 weeks: the 1st week for the pre-treatment period and the 2nd-3rd weeks for the post-treatment. Dry matter intake (DMI) and WI were recorded every day, while urine volume (UV) was determined from day 8 to day 21. Blood and urinary samples were collected on days 6, 14, and 21 of the study for electrolytes and creatinine analysis.Results:The results demonstrated that both DMI and WI were affected by SW1.5 (p<0.05). Goats drinking from SW1.5 had lower DMI during D19–21, and the ratio of DMI/WI was significantly different during D16–21 (p<0.05). Interestingly, the UV from SW1.5 was higher than that from SW0 during D13–21 (p<0.05). Although the body weights (BW) of both groups were similar (p>0.05), the weight gain observed in the SW1.5 group tended to decrease (p=0.056) at the 2nd week. The concentration of electrolytes in blood did not differ between the groups (p>0.05). In contrast, the concentration and excretion of Na+ and Cl- in urine increased in SW1.5 goats at D14 (p<0.05), while creatinine levels in the blood remained normal (p>0.05).Conclusion:The study concluded that crossbred male goats can tolerate 1.5% saline water from diluted SW for 2 weeks. The high salinity in water influences drinking and eating behavior in growing goats. However, the adaptive mechanism by increasing urine output and reducing the reabsorption of Na+ and Cl- in the kidney is the key function and works faster than behavioral responses. The kidney apparently drives drinking behavior during high salinity water consumption.

Electrolyte profiles with induced hypothermia: A sub study of a clinical trial evaluating the duration of hypothermia after cardiac arrest.

BackgroundElectrolyte disturbances can result from targeted temperature treatment (TTM) in out‐of‐hospital cardiac arrest (OHCA) patients. This study explores electrolyte changes in blood and urine in OHCA patients treated with TTM.MethodsThis is a sub‐study of the TTH48 trial, with the inclusion of 310 unconscious OHCA patients treated with TTM at 33°C for 24 or 48 h. Over a three‐day period, serum concentrations were obtained on sodium potassium, chloride, ionized calcium, magnesium and phosphate, as were results from a 24‐h diuresis and urine electrolyte concentration and excretion. Changes over time were analysed with a mixed‐model multivariate analysis of variance with repeated measurements.ResultsOn admission, mean ± SD sodium concentration was 138 ± 3.5 mmol/l, which increased slightly but significantly (p < .05) during the first 24 h. Magnesium concentration stayed within the reference interval. Median ionized calcium concentration increased from 1.11 (IQR 1.1–1.2) mmol/l during the first 24 h (p < .05), whereas median phosphate concentration dropped to 1.02 (IQR 0.8–1.2) mmol/l (p < .05) and stayed low. During rewarming, potassium concentrations increased, and magnesium and ionizes calcium concentration decreased (p < .05). Median 24‐h diuresis results on days one and two were 2198 and 2048 ml respectively, and the electrolyte excretion mostly stayed low in the reference interval.ConclusionsElectrolytes mostly remained within the reference interval. A temporal change occurred in potassium, magnesium and calcium concentrations with TTM’s different phases. No hypothermia effect on diuresis was detected, and urine excretion of electrolytes mostly stayed low.

POS-390 ELECTROLYTE PROFILES OF LUPUS NEPHRITIS PATIENTS TREATED WITH THE NOVEL CALCINEURIN INHIBITOR VOCLOSPORIN

Electrolyte imbalances, which can be modulated within the kidney, have been previously reported with calcineurin inhibitor (CNI) utilization in solid organ transplant.1,2Dietary supplementation of electrolytes may correct serum electrolyte imbalances; therefore, it can be useful to evaluate urinary excretion over time to detect changes in electrolytes due to diet or to confirm clinical findings in serum. Voclosporin is a novel CNI approved in the US for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Data from the pivotal Phase 3 AURORA 1 study showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids results in higher complete renal response rates at one year (40.8% vs 22.5%; OR 2.65; p<0.0001) in patients with lupus nephritis. AURORA 1 was a double-blind, randomized controlled trial designed to evaluate oral voclosporin (23.7 mg twice daily) compared to placebo in patients with active lupus nephritis, with all patients receiving MMF (target dose 1 g twice daily) and low-dose oral steroids (rapidly tapered to 2.5 mg daily at week 16). Serum electrolyte imbalances including hypomagnesemia are common adverse events associated with CNIs. In contrast to these reports, mean serum electrolyte concentrations of patients treated with voclosporin were within normal ranges in AURORA 1. As serum electrolytes concentrations can be impacted by dietary supplementation, we evaluated urinary excretion rates to assess if inadvertent dietary supplementation during the study had impacted the findings in serum. Twenty-four-hour urine samples from 60 patients in each treatment arm were selected including patients that responded to treatment at one year with at least 50% reduction in urine protein creatinine ratio (UPCR) from baseline (treatment responders), those who had not (non-responders), and patients who had at least 30% reduction from baseline in estimated glomerular filtration rate (eGFR) during the study. Mean change from baseline to one year in magnesium, potassium and sodium are presented as 24-hour urinary electrolyte excretion rates. Mean changes from baseline in urinary electrolyte excretion were small for magnesium (≤13.4 mg/24 hours) and potassium (≤6.4 mmol/24 hours) with no significant differences between treatment arms for any of the subgroups. Sodium excretion decreased from baseline in all subgroups (≤30.5 mmol/24 hours) except for responders in the control arm (increase of 14.0 mmol/24 hours) at one year (Table 1). Patients with lupus nephritis in AURORA 1 treated with voclosporin in combination with MMF and low-dose steroids achieved significantly higher complete renal response rates compared to patients treated with only MMF and low-dose steroids. At the doses studied, changes from baseline in urinary electrolyte excretion of magnesium, potassium, and sodium were not clinically meaningful in either treatment arm regardless of response to treatment. These results confirmed dietary supplementation did not impact the findings in serum concentrations. Together with the reported normal electrolyte concentrations in serum, this study confirms voclosporin has no meaningful impact on mean concentrations of electrolytes. This analysis further supports the safety and efficacy of voclosporin for the treatment of patients with lupus nephritis.

Evaluation of nocturnal blood pressure changes and urinary electrolyte excretion in children with enuresis.

Monosymptomatic nocturnal enuresis (MNE) is defined as involuntary nighttime urination of children over five years of age without any congenital or acquired defect in the central nervous system. Many factors, mainly nocturnal polyuria, sleep disorders, decreased bladder capacity, and bladder dysfunctions play a role in the etiology of MNE. Eighty-three children diagnosed with MNE were included in the study. Complete blood cell count, blood biochemistry, renin, and aldosterone levels of all children were obtained. Twenty-four-hour urine samples were collected separately daytime and nighttime and urinary electrolytes were evaluated. Also, 24-hour ambulatory blood pressure monitoring (ABPM) was performed for each patient. The results were evaluated by comparing both enuretic children vs. control group and enuretic children with polyuria vs. without polyuria. When we compared the enuretic children and the control group in terms of urinary electrolytes, the fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) values of the enuretic group were higher than the control. The evaluation of the 24-hour ABPM findings revealed no significant difference in terms of the mean arterial pressure (MAP) and diastolic blood pressure (DBP) during the daytime and nighttime measurements. The daytime systolic blood pressure (SBP), however, was significantly lower in the enuretic group. When enuretic children with and without polyuria and the control group were compared, the nighttime, FENa, FEK, as well as nighttime urinary excretion of calcium and protein were significantly higher in enuretic children with polyuria. No difference was detected on the MAP, SBP, or DBP values. In conclusion, the nighttime urinary solute excretion of enuretic children was found to be higher and this condition may especially be associated with pathogenesis of nighttime polyuria. In enuretic children, nighttime blood pressure changes were not influential in the etiopathogenesis in all patient groups and multiple mechanisms may play a role in the pathogenesis of enuresis.

Evaluation of Diuretic activity of Fractional Extracts of Ajuga remota Benth (Lamiaceae) in Albino mice

The present study was evaluated the in vivo diuretic activity of fractional extracts of A. remota in albino mice. The dried aqueous crude extracts were subjected to soxhlet extraction by n-butanol, methanol and water solvents. The mice were randomly divided into eleven groups with 8 mice in each. All fractions were administered orally at doses of 250, 500 and 1000 mg/kg to adult male mice, and the positive and negative controls were treated with furosemide (10 mg/kg, p.o) and the vehicle distilled water (2 ml/100 gm of body weight) respectively. The diuretic effect of the extracts was evaluated by measuring urine volume, urinary electrolytes and urinary pH. The result indicates that aqueous and methanolic fractions at 1000 mg/kg dose produced significant (p&lt;0.001) increase in urine output and electrolyte excretion (p&lt;0.001) when compared to control. Additionally, potassium sparing activity (27%, p&lt;0.05) and high natriuretic index (2.7-3.03) were produced by the n-butanol fraction relatively even if it showed minimal effect on urine output. Therefore, from the present study it may be concluded that the compounds present in methanolic and aqueous fraction are responsible for diuretic activity. This finding together with previous results on the aqueous crude extracts provides a quantitative basis for developing a new diuretic medicine from A. remota plant.

Whey beverage improves hydrating capacity of the soccer players

The hydration process is critical in soccer players. The hydrating capacity, energy recovery, and electrolyte excretion in urine were determined by the use of a whey beverage as a hydration medium for high-performance athletes compared to the effects of purified water and a sport beverage. The study was carried out through an approved research protocol, which contemplates the determination of hydrating capacity by monitoring body weight during a period of exercise and a subsequent hydration period. Energy recovery was determined by monitoring blood glucose levels and electrolyte excretion was performed by quantifying the concentration of sodium (Na+ ), potassium (K+ ), calcium (Ca2+) and magnesium (Mg2+) in urine samples provided by the participants during the research protocol. It was concluded that the whey beverage has an appropriate capacity for hydration and energy recovery, while with regard to minerals it was observed that it effectively regulates the excretion of Na+ , Ca2+ and Mg2+ .

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

BackgroundFurosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design.ResultsThe most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF).ConclusionsThese results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

Diurnal rhythms of urine volume and electrolyte excretion in healthy young men under differing intensities of daytime light exposure

In humans, most renal functions, including urine volume and electrolyte excretions, have a circadian rhythm. Light is a strong circadian entrainment factor and daytime-light exposure is known to affect the circadian rhythm of rectal temperature (RT). The effects of daytime-light exposure on the diurnal rhythm of urinary excretion have yet to be clarified. The aim of this study was to clarify whether and how daytime exposure to bright-light affects urinary excretions. Twenty-one healthy men (21–27 years old) participated in a 4-day study involving daytime (08:00–18:00 h) exposure to two light conditions, Dim (< 50 lx) and Bright (~ 2500 lx), in a random order. During the experiment, RT was measured continuously. Urine samples were collected every 3 ~ 4 h. Compared to the Dim condition, under the Bright condition, the RT nadir time was 45 min earlier (p = 0.017) and sodium (Na), chloride (Cl), and uric acid (UA) excretion and urine volumes were greater (all p < 0.001), from 11:00 h to 13:00 h without a difference in total daily urine volume. The present results suggest that daytime bright light exposure can induce a phase shift advance in urine volume and urinary Na, Cl, and UA excretion rhythms.

419-P: Correlation between 24-Hour Urinary Electrolyte and Urinary Albumin in Patients with Type 2 Diabetes

Objective: To explore the characteristics of 24-hour urinary electrolyte excretion in patients with type 2 diabetes mellitus (T2DM), and its correlation with urinary albumin and early renal injury. Methods: A total of 1475 T2DM and 265 nondiabetic patients (ND group) from 2018 to 2020 were enrolled. According to the urinary albumin excretion rate (UAER), T2DM patients were divided into normal albuminuria group (NA group): UAER &amp;lt; 30mg/24h; Microalbuminuria group (MA group): UAER 30~300 mg/24 h; massive albuminuria group (PR group): UAER &amp;gt; 300mg/24h. The characteristics of 24h urinary electrolyte excretion in different groups were observed and the correlation between 24h urinary electrolyte excretion and urinary albumin was analyzed. Results: We found that 24h urinary potassium, sodium, chlorine, phosphorus and magnesium in all subgroups of T2DM were higher than those in ND group (P &amp;lt; 0.001), 24h urinary calcium in ND group was higher than that in PR group (4.3±2.1 vs. 3.2±2.5, P &amp;lt; 0.001), but lower than that in NA group (4.3±2.1 vs. 4.7±2.8, P &amp;lt; 0.001). As urinary albumin increased, 24h urinary calcium of T2DM patients showed a decreasing trend while the other urinary electrolytes showed an increasing trend (P &amp;lt; 0.001). Urinary albumin was positively correlated with 24h urinary potassium, sodium, chlorine, phosphorus, magnesium (r=0.133~0.169, P &amp;lt; 0.001) and negatively correlated with 24h urinary calcium (r= -0.130, P &amp;lt; 0.001). Multiple linear regression showed that 24h urinary potassium was an independent influencing factor of urinary albumin (β = 0.178, P &amp;lt; 0.001). Conclusion: There is a difference in 24h urinary electrolyte excretion between T2DM and nondiabetic patients. The urinary electrolyte excretion of T2DM patients varies with urinary albumin. 24h urinary electrolyte excretion changes before the appearance of albuminuria, which may be an indicator of early renal injury. High urinary potassium may serve as a parameter to predict early diabetic nephropathy. Disclosure Y. Wang: None. M. Zhang: None. H. Li: None. S. Qu: None.

Plasma Renin Activity after Diuretic Treatment in Patients with Stable Heart Failure: With Special Reference to its Association with Electrolyte Chloride

A recent study reported an intimate association between urinary chloride (Cl) and plasma renin activity (PRA) in acute heart failure (HF) status, reflecting normal functioning of the ‘tubulo-glomerular feedback’ mechanism. Whether the ‘tubuloglomerular feedback’ mechanism functions normally in stable HF status, however, is unclear. This study examined whether the ‘tubulo-glomerular feedback’ mechanism functions normally under resolution of worsening HF after decongestive therapy. Data from 26 patients with acute HF and its recovery after decongestive therapy were analyzed. Clinical tests included measurement of peripheral blood tests, serum and spot urinary electrolytes, plasma neurohormones, and fractional urinary excretions of electrolytes. In a total of 26 patients, PRA increased after acute HF treatment (from 1.64±2.0 to 5.48±6.1 ng/ mL/h, p=0.002). Changes in the serum logPRA and urinary Cl concentration from worsening to its recovery tended to be inversely correlated (R2 =0.12, p=0.085) and logPRA and the serum Cl concentration at recovery were inversely correlated (R2 =0.23, p=0.01). When divided into 2 groups (n=13 in each) according to the median PRA, the group with greater PRA changes showed a larger decrease in the urinary Cl concentration (from 110±44 to 72.8±38, p=0.03). The group with higher PRA at recovery showed a lower serum Cl concentration than the group with lower PRA at recovery (102±6.5 vs 107±4.2 mEq/L, p=0.04). In conclusion, the association between PRA and the serum/urinary Cl concentration is blunted in stable HF under-decongestive therapy, possibly due to the physiologic status under full cardiovascular medication compared with that in acute HF status.