Urinary Electrolyte Levels Research Articles

Balancing sodium and potassium: Implication of mTORC2-mediated ENaC activation in DCT2 and early CNT for potassium balance in high dietary potassium

Background: The activity of the epithelial sodium ion channel, ENaC, and ENaC-dependent potassium (K+) secretion through ROMK are influenced by both aldosterone-dependent and independent mechanisms in response to dietary potassium (K+). While ENaC activity in the late connecting tubule (CNT) and cortical collecting duct (CCD) depends on aldosterone, it is aldosterone-independent in the late distal convoluted tubule (DCT2) and early CNT (eCNT). Aldosterone-stimulated ENaC activity relies on SGK1, transcriptionally upregulated by aldosterone and subsequently phosphorylated and activated by mTOR complex-2 (mTORC2). Recent evidence suggests that high potassium can rapidly activate mTORC2/SGK1 signaling to stimulate ENaC. In this study, we explore mTORC2’s role in K+ secretion and aldosterone-independent ENaC regulation. Methods: Rictor, a core component of mTORC2, was selectively knocked out (KO'd) in DCT2, CNT and CD by utilizing Calbindin as Cre-driver (CRKO mice) or late CNT and CD, by employing AQP2 as the Cre-driver (ARKO mice). Both wild-type (WT) and KO mice were subjected to a high potassium (HK) diet for short-term (4 hours) or medium-term (48 hours) periods, enabling the monitoring of both the early response and prolonged adaptation to the HK diet. Parameters assessed include urinary and blood electrolyte levels, renal transporter expression, activity and localization, and mTORC2 target phosphorylation. Results: On a normal K+ diet, both KO mice maintained Na+ and K+ balance but CRKO mice had elevated aldosterone levels. After short-term (4-hour) HK intake, CRKO mice had disrupted Na+ and K+ balance, reduced K+ excretion and hyperkalemia. In contrast, ARKO mice maintained Na+ and K+ balance with elevated aldosterone. On a prolonged HK diet (48 hours), CRKO mice had severe hyperkalemia, reduced GFR and significantly elevated aldosterone level. Immunofluorescence studies indicated markedly reduced apical localization of active ENaC in DCT2/eCNT of CRKO mice. Conversely, ENaC apical localization in the late CNT and CCD was mostly unaffected. Phosphorylation of mTORC2 targets involved in ENaC regulation, such as SGK1, and SGK1’s target, Nedd4-2, was also reduced in CRKO mice. ARKO mice maintained ion balance with normal K+ levels but significantly increased aldosterone levels and maintained ENaC apical localization in the late CNT and CCD. Conclusions: The data suggest that high aldosterone can compensate mTORC2 deficiency and maintain ENaC activity in the late CNT and CCD. However, mTORC2 activity is crucial for maintaining ENaC activity in the late DCT and early CNT (aldosterone-independent) and preserving potassium balance during high dietary potassium intake. National Institutes of Health (R01- DK56695), James Hilton Manning and Emma Austin Manning Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evaluation of Tribulus terrestris effect on kidney and liver function in healthy mice

This research aims to evaluate the pharmacological efficacy of aqueous spine extracts of Tribulus terrestris (TT) on liver and kidney function through physiological, biochemical, haematological, and histological assessments. Tribulus terrestris is renowned for its therapeutic benefits in traditional medicine practices in China, India, Pakistan, and Sudan for treating various chronic ailments. The study employed 5 weight per volume percentage (% w/v) of TT aqueous spines extract. BALB/c mice, both male and female, aged 4-6 weeks, were maintained in controlled ecological conditions (temperature: 22-24°C, humidity: 50-70%, light/dark cycle: 12-h). The mice were divided into two groups: the control group received normal tap water throughout the experimental period, while the other group was administered 5% (w/v) TT spines solution for 15 days. The outcomes of BALB/c mice treated with 5% Tribulus terrestris were compared with the control group after 15 days, revealing no significant difference in the drug's efficacy. The physiological results indicated reduced body weight, food intake, and adverse effects in the biochemical profile, including urinary and serum electrolyte levels, liver function tests, increased random blood glucosem, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin (BIL), cholesterol (CHO), high-density lipoprotein (HDL), and triglycerides (TRI). Similarly, kidney function tests showed increased Urinary Nitrogen and creatinine plasma levels, with low blood urea nitrogen (BUN), urinary creatinine, and glomerular filtration rate (GFR). However, no significant difference was observed in haematological profile readings. In conclusion, the findings suggest that the aqueous spine extract of Tribulus terrestris does not demonstrate beneficial effects on liver and kidney function, indicating that this study supports the notion that the plant cannot be utilized as a medicinal remedy.

Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.

Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.

Ameliorative Effect of Multi Herbal Formulation on Lipid Peroxidation and Redox Dysfunction in Ethanol Induced Hepatic Imbalance

Abstract: Introduction: Urolithiasis has afflicted human race since the days of yore. Conventional treatment acts only on associated ailments whereas pharmacologically active phytoconstituents derived from plants are reported to possess lithotriptic as well as anti-urolithiatic effect, thus herbal sources need to be scientifically explored. Present study was aimed to evaluate anti-urolithiatic potential of leaves of Alstonia scholaris and its isolated pentacyclic triterpenoids: lupeol and ursolic acid in ethylene glycolinduced renal calculi rat model. Materials and Methods: Leaves of Alstonia scholaris were extracted with various solvents, amount of triterpenoids in each extract was quantified using HPTLC. Extract which had higher amount of triterpenoid was evaluated for its anti-urolithiatic effect. Albino wistar rats of either sex were divided into 6 groups. All groups except vehicle were fed with 0.75%v/v of ethylene glycol for 28 days. Treatment with standard cystone, low and high dose of extract and pentacyclic triterpenoids were given to respective groups from 4th-28th day of study. On 28th day, serum creatinine, uric acid, BUN, TNF-α, IL-6 and urinary electrolyte levels were estimated. Kidneys were isolated, one was used for histopathological study and other for antioxidant assays. Results and Discussion: Histopathological examination of kidneys revealed destructed morphology due to deposition of large polymorphic crystals and cystic dilatation of tubules. Whereas treatment with extract and its pentacyclic triterpenoids prevented renal damage and deposition of crystals. Perturbations in levels of nitrogenous wastes, inflammatory mediators and urinary electrolytes were also prevented. Alstonia scholaris rich in triterpenoid significantly arrested associated oxidative stress and inflammation thus preventing formation of renal calculi. Conclusion: Leaves of Alstonia scholaris and pentacyclic triterpenoids isolated from them demonstrates potent herbal remedy for treatment of urolithiasis. Key words: Alstonia scholaris, Anti-inflammatory, Lupeol, Oxidative stress, Ursolic acid, Urolithiasis.

Chemical composition, antioxidant activity, and diuretic effect of Moroccan fresh bee pollen in rats.

Aim:This study investigated the chemical composition, antioxidant activity, and diuretic effect of Moroccan aqueous extract of fresh bee pollen (AEFBP) in normal rats.Materials and Methods:The chemical composition of the extracted bioactive compounds was assessed using liquid chromatography with diode array detection coupled to electrospray ionization (ESI) tandem mass spectrometry (LC/DAD/ESI-MSn). 2,2-diphenyl-1-picrylhydrazyl and the reducing power were used to assess the antioxidant properties of the extract, together with the determination of total phenols and flavonoids. To assess the diuretic effect, 20 normal rats were divided into five groups: The first was a control group administered by distilled water (10 mL/kg body weight), the second group received furosemide (10 mg/kg body weight), the third group received 100 mg/kg body weight of AEFBP, the fourth group received 250 mg/kg body weight of AEFBP, and the fifth group received 500 mg/kg body weight of AEFBP for 30 days. Toward the end of this experiment, urine output was measured, and plasma and urine were sampled to analyze creatinine, potassium, chloride, and sodium levels.Results:N1,N5,N10-tri-p-coumaroylspermidine is a spermidine derivative and was the main compound in this sample, in a total of 19 compounds identified, including flavonoids, glucoside flavonoids, and methylated derivatives. Force feeding with the AEFBP induced a significant increase in urine output and urinary electrolyte levels with a dependent dose-effect without changes in plasma electrolytes, whereas furosemide decreased plasma potassium.Conclusion:Moroccan fresh bee pollen extract contains flavonols and spermidines that induce a potential antioxidant activity related to significant diuretic effect without changes in plasma composition.

Corallodiscus flabellata B.L. Burtt Extracts Stimulate Diuretic Activity and Regulate the Renal Expression of Aquaporins

Corallodiscus flabellata B. L. Burtt is a traditional Chinese medicine. Previous studies in our laboratory showed that C. flabellata alleviated symptoms of Alzheimer's disease (AD) in a rat model of AD and increased healthy rats' urine volume. The aims of this study were to explore the diuretic activity of different extracts from C. flabellata and to identify the underlying mechanisms of action. Different doses of a C. flabellata extract (CF-L, CF-M, and CF-H) were administered orally to male KM mice in a single dose. In another procedure, C. flabellata (CF), water extract, and 20%, 30%, and 40% ethanol extracts of C. flabellata (CF-WE, CF-20, CF-30, and CF-40) were administered orally daily for 5 days. The urinary excretion rate, osmolality, and electrolyte levels in urine and serum, renal expression of aquaporins (AQPs), apoptosis-related protein, and MAPK-related protein were analyzed. The results showed that single doses of CF-M and CF-H increased urinary volume significantly, as well as daily administration of CF, CF-WE, CF-20, CF-30, and CF-40. Furthermore, CF-20 and CF-30 increased the concentration of Na+ in the urine. Treatment with CF-40 increased the urine osmolality and Na+ and Cl− concentrations and decreased the concentration of Na+ in the serum. Also, CF, CF-WE, CF-20, CF-30, and CF-40 decreased the renal expression of AQPs, as well as the ratios of Bcl-2/Bax, p-ERK/ERK, p-JNK/JNK, and p-p38/p38. In sum, the medium and high doses of the C. flabellata extract and CF-WE, CF-20, CF-30, and CF-40 were found to have a diuretic activity. They may inhibit the renal expression of AQPs and apoptosis-related proteins by inhibiting the MAPK signaling pathway, thereby achieving diuretic effects.

P.759 Pharmacological inhibition of miRNA metabolism regulating enzyme Dicer deteriorates long-term memory formation

Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD.Phase 2, randomized, controlled, open-label, crossover trial.Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs) > 15 mL/min/1.73 m2 and residual proteinuria with protein excretion ≥ 0.5 g/24 h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy.After stratification by serum phosphate level, ≤4 or >4 mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600 mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period.The primary outcome was 24-hour proteinuria (n = 49 patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness.Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24 h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24 h) sevelamer were similar (P = 0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer.Short treatment duration, lower pretreatment proteinuria than expected.3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria.Sanofi (Milan, Italy).Registered at ClinicalTrials.gov with study number NCT01968759.

SAT-307 NORMAL FETAL KIDNEY VOLUME AND INFANT URINALYSIS IN OFFSPRING OF WOMEN TREATED FOR GESTATIONAL DIABETES

The worldwide prevalence of gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is increasing, and affects up to 20% of pregnancies. Evidence from animal studies indicate that maternal hyperglycemia can be detrimental to renal development and kidney function in exposed offspring. In humans, renal dysfunction and disease has been reported in adults whose mothers had Type 1 or Type 2 diabetes, suggesting that pre-gestational maternal diabetes influences kidney development and the risk of renal dysfunction in adulthood. Despite its high prevalence, few studies have examined kidney development or renal function in offspring of women with GDM. The aim of this study was to evaluate the impact of treated GDM on fetal kidney size and infant renal physiology. A prospective cohort study was conducted between June 2013 and August 2016 in Melbourne, Australia. Participants were recruited at a large public university teaching hospital and clinical data were collected from women without GDM (n=82) and women diagnosed and treated for GDM (n=76). GDM was diagnosed by routine screening at 26-28 weeks gestation. Women with GDM received specialist support for glucose monitoring, diet and exercise in addition to routine antenatal care. One-third of women with GDM also required insulin therapy. Participants underwent an obstetric ultrasound at 32-34 weeks gestation for fetal biometry and fetal kidney volume measurement. Quantitative urinalyses were performed in infant urine samples at 3 months of age for analysis of protein and electrolytes. Maternal age, weight and body mass index were similar in no-GDM and GDM women. Estimated fetal weight and birth weight were also similar in no-GDM and GDM pregnancies. There were no differences in fetal kidney dimensions, total kidney volume, infant urinary albumin or electrolyte levels. Fetal kidney size did not differ by mode of GDM treatment (i.e. diet and exercise alone, or diet and exercise with insulin therapy). There were no associations between maternal glucose levels at screening and fetal total kidney volume or infant urine albumin in multivariable regression analyses. Findings suggest that a limited period of hyperglycemia prior to diagnosis and treatment of GDM in women attending a large metropolitan public hospital in Australia does not alter fetal kidney volume at 32-34 weeks gestation or urinalysis in 3-month-old infants, a favourable finding considering the increasing number of women diagnosed with GDM.

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial

Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Phase 2, randomized, controlled, open-label, crossover trial. Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. After stratification by serum phosphate level,≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Short treatment duration, lower pretreatment proteinuria than expected. 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Sanofi (Milan, Italy). Registered at ClinicalTrials.gov with study number NCT01968759.

MON-373 Pseudohypoaldosteronism Type 1, a Masquerader: Case Study

Background: Pseudohypoaldosteronism (PHA) Type 1 usually present in the newborn period as failure to thrive, hyponatremia and hyperkalemia. The spectrum of manifestation however ranges from asymptomatic to severe. Initial presentation may be easily confused with more common disease process like poor feeding with inadequate calorie intake, dehydration, Congenital Adrenal Hyperplasia (CAH), adrenal insufficiency (AI), urinary tract abnormality and hypoaldosteronism. Patients with PHA Type 1 have supraphysiological aldosterone and renin levels appropriate for the electrolyte abnormality but ineffective due to an abnormality in mineralocorticoid receptor or epithelial sodium channel (ENaC). Clinical case: We present a Caucasian female who was admitted for failure to thrive. At 3 weeks of age, she was found to have lost 14.5% of birth weight. She was afebrile and there was no vomiting. She had hyperkalemia, hyponatremia, hypercalcemia, and mild transaminitis (Na 129mmol/L (134-142mmol/L), K 6.8mmol/L (4-6.2mmol/L), Cl 91mmol/L (96-110mmol/L), Ca 11.8mg/dl (9-10.9mg/dl), ALT 35unit/L (8-32 units/L) with increased urine output (6-6.5ml/kg/hr (4-5ml/kg/hr). Genital examination, newborn screen, ECG, renal US, thyroid function, 17-OH progesterone, and ACTH stimulation tests were normal. No family history of similar electrolyte abnormalities. Treatment with sodium containing IVF and kayexalate improved her electrolytes. Her diagnosis at discharge was inadequate calorie intake and dehydration. Increased calorie intake resulted in continuous weight gain and resolution of electrolyte abnormality at discharge (Na 137mmol/L, K 5.6mmol/L, Cl 97, Ca 10.8mg/dl). Despite improvement in weight gain and being asymptomatic, follow up outpatient monitoring of electrolyte levels showed persistent hyponatremia and hyperkalemia (Na 129 mmol/L, K 7.8mmol/L). No gastrointestinal symptoms or skin abnormalities. Given her electrolyte abnormalities, the differential diagnoses included SIADH, Adrenal Insufficiency and hypoaldosteronism. The diagnosis of PHA Type 1 was made based on increased aldosterone and renin levels (Aldosterone 1031ng/dl (5-90ng/dl), Renin 277pmol/L (2-37pmol/L). She was started on oral Nacl supplement and high dose fludrocortisone resulting in resolution of electrolyte abnormality. Genetic evaluation is underway. Conclusion: PHA Type 1 is a rare clinical entity that can masquerade as other more common causes of malnutrition and electrolyte abnormality. Delay in prompt diagnosis and treatment of PHA Type 1 can be associated with morbidity and mortality. Follow up monitoring of serum and urine electrolyte levels is important in children presenting with malnutrition and electrolyte abnormalities to enable early recognition and adequate treatment initiation.

OP.LB.02

Objective: Stroke-prone spontaneously hypertensive rats (SHRSP) are a model of chronic hypertension relative to normotensive Wistar-Kyoto rats (WKY). Our studies on urinary protein and electrolyte levels have shown kidney dysfunction and impaired water balance in pregnant SHRSP. We investigated whether urinary peptidomics can identify target molecules involved in kidney dysfunction in pregnant SHRSP. Design and method: We analyzed urine of non-pregnant and pregnant WKY and SHRSP (n = 7) at 0th, 12th and 18th gestational day (GD) using capillary electrophoresis on-line coupled to ESI-TOF-MS. Peptide sequencing was performed in LTQ-Orbitrap™ hybrid mass spectrometer. Quantitative PCR was carried out in kidney specimens of non-pregnant and pregnant WKY and SHRSP (n = 5). Results: The longitudinal comparison within and between WKY and SHRSP at GD0, GD12 and GD18 detected 1228 differentially expressed peptides (p < 0.05, Mann-Whitney test). Repeated measure ANOVA analysis of these peptides identified 46 peptides which were significantly regulated at all time-points and 77 peptides only at GD12 and GD18. In total 43 and 42 peptides markers were down- and up- regulated respectively, at all time-points; while 38 peptides were down-regulated at either, GD12 or GD18 or both, in SHRSP compared to WKY (fold change >1.5, p < 0.05). Peptide sequencing showed fragments of collagen alpha-chains, serum albumin, pro-thrombin, actin, Serpin A3K, pro-epidermal growth factor and uromodulin. Uromodulin peptides showed no significant difference at GD0 while there was 7.8 (p = 0.018) and 8.8 (p = 0.050) fold change increase at GD12 and GD18 respectively, in SHRSP compared to WKY. These results were reflected in mRNA level of uromodulin. No significant change between GD0 and GD18 WKY were identified, while GD0 and GD18 SHRSP showed significant changes (RQ 3.2 ± 0.064, p 0.002 and RQ 6.1 ± 0.048, p 0.0005, respectively). Conclusions: We observed a characteristic peptidomic pattern which was altered in response to both pregnancy and hypertension. Uromodulin is a candidate gene for human hypertension and renal dysfunction but, as yet has not been shown to play a role in hypertensive pregnancy. Our findings suggest that uromodulin may be a novel candidate involved in kidney dysfunction during hypertensive pregnancy.

Abnormal circadian blood pressure regulation in children with nocturnal enuresis

Introduction: To investigate autonomic nervous system function in enuretic children by performing ambulatory blood pressure monitor (ABPM) for 24 h. Methods: Twenty-eight children ranging in age from 6 to 15 years with primary nocturnal enuresis and 27 age-matched healthy controls were enrolled and they get 24 h ABPM. Hypertension was defined as standard deviation score (SDS) > 1.64 (i.e., >95th percentile) adjusted for gender and height. Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were carried out in all children. They have also requested to have a diary about daily fluid intake and urine volume. Results: Although the mean 24-h and daytime diastolic blood pressure (BP) did not differ between the groups, systolic BP (SBP) was significantly higher in enuretic children (p < 0.05). The mean night-time SBP, DBP values, SDS and BP loads were found to be significantly higher than those in the controls (p < 0.01). A lack of nocturnal decrease was more prevalent in the enuretic children compared with the control subjects, the difference was statistically significant for DBP but not for SBP. Patients with elevated night-time BP load was found to have higher frequency of urinary incontinence per week as well as per night when compared with enuretic children with normal night-time BP load (r = 0.72, r = 0.69, p < 0.01, respectively). Conclusion: Subtle abnormalities of circadian BP regulation in enuretic children indicated by a selective elevation of nocturnal SBP, DBP, and MAP, and attenuated nocturnal dipping may reflect sympathetic hyper activation and its possible role in pathogenesis of enuresis.

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children. Materials and Methods : In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine. Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value>0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value 0.05). Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE. Keywords : Child; Enuresis; Blood pressure; Autonomic dysfunction

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children.Materials and Methods: In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine.Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value&gt;0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value&lt;0.05) but did not differ between the groups during the daytime (p-value&gt;0.05).Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE.Keywords: Child; Enuresis; Blood pressure; Autonomic dysfunction

Evaluation of the diuretic and urinary electrolyte effects of methanolic extract of Peganum harmala L. in Wistar albino rats.

The use of traditional medicines as a diuretic agent has been increasing in recent years. The diuretic activity of a number of plant extracts used as diuretic agents in ethnomedicine has been confirmed in experimental animals. However, despite the widespread use of Peganum harmala in traditional medicine, there is a paucity of data supporting its use as a diuretic agent. Therefore, the present study aimed to envisage the true effect and magnitude of diuresis of methanolic extract of P. harmala (MEPH) in comparison with a well-known diuretic drug furosemide using Wistar albino rats. MEPH was administered orally in three different doses (150, 300 and 450 mg/kg) to experimentally dehydrated rats. Furosemide (10 mg/kg orally) was used as a reference drug. The diuretic effect of the MEPH was evaluated by measuring urine volume, urine pH, urinary electrolyte levels, natriuretic and saliuretic effects. The urine volume (in mL) measured at 5 h and 24 h and electrolyte excretion (Na+, K+, and Cl−) at 24 h duration were measured. The urine output and urinary electrolyte excretion were found to be significantly higher in rats treated with MEPH as compared to normal rats in a dose dependent manner (P < 0.05). The results of our study were comparable to furosemide drug. Based on observed results, we can recommend that P. harmala may be an effective diuretic, however, toxicity studies should be conducted before administration.

Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat.

Overactivity of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. Catheter-based renal nerve ablation for the treatment of drug-resistant hypertension has recently been developed. An alternative strategy for the modulation of sympathetic nerve function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting dopamine β-hydroxylase (DβH), the enzyme that catalyzes the conversion of dopamine (DA) to NA in the sympathetic nerves. Renal denervation (RDN) surgery was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on the DA and NA levels and on blood pressure over a 28-day period. The selective peripheral DβH inhibitor etamicastat (30 mg kg (-1)day(-1)) was administered to another cohort of SHR. RDN and etamicastat treatment had no effect on the renal function, as assessed by measuring the water balance response, renal function and urinary electrolyte levels. RDN significantly decreased the systolic blood pressure (SBP) and the diastolic blood pressure (DBP). A gradual return of the SBP and the DBP to the high baseline levels was observed over time. Conversely, treatment with etamicastat resulted in a significant decrease in the SBP and the DBP at all time points. On the last day of the assessment, NA levels in renal tissue were significantly decreased in both RDN and etamicastat-treated groups. In contrast, the NA levels in the left ventricle were decreased only in the etamicastat-treated group. Thus, RDN produces transitory decreases in blood pressure, whereas prolonged downregulation of sympathetic drive with the DβH inhibitor etamicastat results in a sustained decrease in the SBP and the DBP.

Cyprinid herpesvirus-3 (CyHV-3) disturbs osmotic balance in carp (Cyprinus carpio L.)—A potential cause of mortality

Cyprinid herpesvirus-3 (CyHV-3) causes a fatal disease in carp (Cyprinus carpio) and its ornamental koi varieties which seriously affects production and trade of this fish species globally. Up to now, the pathophysiology of this disease remains unclear. Affected individuals develop most prominent lesions in gills, skin and kidney, in tissues which are involved in the osmotic regulation of freshwater teleosts. Therefore, here serum and urine electrolyte levels were examined during the course of an experimental infection of carp with CyHV-3. In infected carp an interstitial nephritis with a progressive deterioration of nephric tubules developed, which was paralleled by elevated electrolyte losses, mainly Na+ in the urine. The urine/plasma ratio for Na+ increased from 0.03 in uninfected carp to 0.43–0.83 in carp under CyHV-3 infection, while concentration of divalent ions were not significantly changed. These electrolyte losses could not be compensated since plasma osmolality and Na+ concentration dropped significantly in CyHV-3 infected carp. This was most probably caused by the progressive deterioration of the branchial epithelium, which in teleosts plays a prominent role in osmoregulation, and which was seen concomitantly with decreasing electrolyte levels in the serum of carp under CyHV-3 infection.Immediately after infection with CyHV-3, by day 2 post exposure, affected carp showed severe anaemia and prominent leucocytosis indicating the development of an acute inflammation, which could intensify the observed hydro-mineral imbalances.The data presented here show that an infection with CyHV-3 induces an acute inflammation and a severe dysfunction of osmoregulation in affected carp or koi, which may lead to death in particular in the case of acute disease progression.

Gitelman syndrome during pregnancy – from diagnosis to treatment: a case series and review of the literature

Abstract Objective: Gitelman syndrome (GS) is a rare renal disease, originating from a defect in the Na-Cl co-transporter in the distal tubule, which causes hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and low-normal blood pressure. Mild hypokalemia of pregnancy is physiological. Fatigue, nausea, vomiting, polyuria and low blood pressures are also common complaints associated with a normal pregnancy. Therefore, the diagnosis of an organic renal disorder, i.e., GS, may go undetected, until severe hypokalemia and possible life-threatening cardiac arrhythmias develop. Maternal consequences are obvious. The possibility of fetal pathology remains unclear. Study design: In this study, we describe nine pregnancies in seven women with a clinical diagnosis of GS. Nearly all women were diagnosed initially during pregnancy. We describe their clinical presentation, serum and urine electrolyte levels during pregnancy and immediately post-partum, their treatment and pregnancy outcome. Results: Fetal pregnancy outcomes were mostly favorable. While it is likely that women suffering from GS do not require special fetal surveillance, they are at high risk for electrolyte depletion and thus aggravation of GS during pregnancy. Conclusion: Clinical suspicion of GS should arise in all women presenting with symptomatic hypokalemia. Once the diagnosis is made, adequate supplementation and routine maternal monitoring should ensue.

Acute Hyperkalemia Associated with Inhalation of a Potent ENaC Antagonist: Phase 1 Trial of GS-9411

Inhaled epithelial sodium channel (ENaC) blockers are designed to increase airway surface liquid volume, thereby benefiting cystic fibrosis patients. This study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of ENaC blocker GS-9411, in healthy participants. This randomized, double-blind, placebo-controlled, parallel-group, residential, Phase 1 study evaluated inhaled GS-9411 (2.4, 4.8, and 9.6 mg) or placebo, dosed twice daily for 14 days. GS-9411 was well tolerated; 86.1% of treated participants completed dosing (n=31/36). Cough and dizziness (27.8% participants each; most of mild severity) were the most commonly reported adverse events and occurred in both placebo and GS-9411 treatment groups. Arrhythmias were not observed for GS-9411-treated participants, and electrocardiographic changes were not considered clinically significant. Serum potassium levels exceeded the upper limit of normal (>5 mmol/L), 4 hr after the morning dose in GS-9411 (n=16/24) and placebo (n=4/12) treatment groups (38 incidences total). Retesting revealed levels had returned to normal within 2-3 hr. In urine electrolyte analyses, obtained 0-6 hr after the Day 1 morning dose, mean sodium/potassium ratios significantly increased from values 0-6 hr before dosing. Increased urine sodium/potassium ratios corresponded with high urine concentrations of active GS-9411 metabolites, which inhibited sodium reabsorption in the kidney, leading to the observed transient hyperkalemia in these participants. Inhaled GS-9411 was well tolerated except for the emergence of transient clinically significant hyperkalemia; this finding resulted in termination of further clinical development of this drug and will necessitate development of a new generation of ENaC blockers, which provide a sustained improvement in mucociliary clearance, while reducing renal exposure to ENaC blockade. Transient increases in mean urine sodium/potassium ratios appeared to be the first signal of electrolyte imbalances resulting from drug-induced block of ENaC in the kidney. The results of this study strongly suggest that clinical trials of novel ENaC blockers will require intensive measurement of plasma and urine electrolyte levels.

Protective role of silymarin against manganese‐induced nephrotoxicity and oxidative stress in rat

Metal toxicity may occur after exposure from many sources. Oxidative stress is thought to be involved in manganese-induced toxicity and leads to various health disorders. Silymarin (SIL), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to assess the toxicity of manganese (Mn) on oxidative stress and DNA damage in the kidney of rats and its alleviation by SIL. Manganese was given orally in drinking water (20 mg MnCl2 /mL) with or without SIL administration (100 mg /kg intraperitoneally) for 30 days. Our data showed that SIL significantly prevented Mn induced nephrotoxicity, indicated by both diagnostic indicators of kidney injury like plasma urea, uric acid and creatinine and urinary electrolyte levels and by histopathological analysis. Moreover, Mn-induced profound elevation of the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. This is evidenced by the increase of lipid peroxidation, protein carbonylation, DNA fragmentation and urinary hydrogen peroxide, while, the activities of enzymatic antioxidant and glutathione level were decreased. Treatment with SIL reduced the alterations in the renal and urine markers, decreasing lipid peroxidation markers, increasing the antioxidant cascade and decreasing the Mn-induced damage. All these changes were supported by histopathological observations. These findings suggested that the inhibition of Mn-induced damage by SIL was due at least in part to its antioxidant activity and its capacity to modulate the oxidative damage.