Urinary Electrolyte Research Articles

The Calcium-Sensing Receptor in the Thick Ascending Limb and the Renal Response to Hypercalcemia.

The parathyroid calcium-sensing receptor (CASR) controls the release of parathyroid hormone (PTH) in response to changes in serum calcium levels. Activation of the renal CASR increases urinary calcium excretion and is particularly important when CASR-dependent reductions in PTH fail to lower serum calcium. However, the role of the renal CASR in protecting against hypercalcemia and the direct effects of chronic CASR activation on tubular calcium handling remains to be fully elucidated. Experimental hypercalcemia was induced using the Vitamin D analog (Dihydrotachysterol, DHT) in mice with Ksp-Cre dependent deletion of the Casr (Ksp-Casr) in kidney with Cre negative littermates (WT) serving as controls. Urinary and fecal electrolyte determinations, dual-energy x-ray absorptiometry, molecular and biochemical evaluation, and in vitro tubule microperfusion were performed in both sexes. Ksp-Cre-driven Casr deletion strongly reduced CASR abundance in the thick ascending limb (TAL). At baseline, no marked differences were detected in electrolyte handling and tubular permeability characteristics across the TAL. 3 days of DHT administration induced hypercalcemia in both WT and Ksp-Casr mice. However, while WT mice developed hypercalciuria, this response was absent in Ksp-Casr mice. Urinary excretion of magnesium and other electrolytes did not differ between hypercalcemic WT and Ksp-Casr mice. Intestinal electrolyte absorption was comparable between the two groups. Microperfusion of isolated cortical TALs revealed no baseline differences in the transepithelial voltage, resistance, or ion permeabilities. Following hypercalcemia, transepithelial resistance increased and calcium permeability markedly decreased in WT mice, but not in Ksp-Casr mice, with only minor alterations in magnesium permeability and no changes in transepithelial voltage. In hypercalcemic mice, absence of the CASR in TAL prevented the increase in urinary calcium excretion. The CASR specifically regulated the paracellular permeability of the TAL, especially for calcium.

The direct and urinary electrolyte-mediated effects of ambient temperature on population blood pressure: A causal mediation analysis.

High ambient heat can directly influence blood pressure (BP) through the vasodilation of the skin vasculature and indirectly by affecting urinary volume and electrolyte levels. We evaluated the direct and urine electrolyte-mediated effects of ambient temperature on BP. We pooled 5,624 person-visit data from a community-based stepped-wedge randomized control trial in southwest coastal Bangladesh from December 2016 to May 2017. Same-day ambient temperature data from local weather stations were linked to participant BP and urine electrolytes using geo-locations of their residential addresses. We implemented causal mediation analyses using the product methods of coefficients with linear mixed models under the sequential ignorability assumption. Separate models were run for each urinary electrolyte mediator (sodium, potassium, calcium, and magnesium), followed by combined models to evaluate the natural direct and electrolyte-mediated indirect effects of temperature on BP. Models had participant-level random intercepts and were adjusted for age, sex, body mass index (BMI), religion, exercise, smoking status, sleep hours, alcohol consumption, urine creatinine, time trend, household assets, drinking water salinity, and seasonality. For the combined mediators (sodium, potassium, calcium, and magnesium), for every 5°C increase in average daily temperature: the direct effect on systolic BP was -1.42 (95% CI: -1.94, -0.92) mmHg and urine sodium mediated effect was -0.12 (95% CI: -0.20, -0.05) mmHg; while urine potassium mediated effect was 0.15 (95% CI: 0.08, 0.25) mmHg; urine calcium-mediated effect 0.06 (95% CI: 0.01, 0.12) mmHg; and urine magnesium mediated effect -0.00 (95% CI: -0.03, 0.02) mmHg. We detected similar associations for diastolic BP, pulse pressure, and mean arterial pressure. We found a significant inverse direct effect of ambient temperature on BP compared to minimally mediated urine electrolyte effects. Further studies are needed to uncover the underlying mechanisms of ambient heat and BP associations and to describe the clinical consequences of these associations.

Impact of Almond (Terminalia catappa) Ethanolic Leaf Extracts on an Ethylene Glycol-Induced Urolithiasis Rat Model

The disease of renal stones has been recognized for centuries. It is one of the most common disorders, characterized by calcifications in the kidneys, bladder, or urethra. Phytomolecules are effectively used in traditional medicine. The current study aimed to evaluate the effects of high and low doses of Terminalia catappa (T. catappa) leaf extracts on renal stone formation in a rat model of urolithiasis. The rats werehoused individually in metabolic cages and were given drinking water containing 0.75% Ethylene Glycol (EG) and 1% Ammonium Chloride (AC) to induce the production of kidney stones. EG and AC elevated the levels of molecules indicative of renal efficiency, including citrate, oxalate, urobilinogen, and microalbumin. Additionally, they reduced urine volume and urinary pH. After administering (200 or 400 mg/kg body weight) of Cystone or ethanolic extracts of T. catappa leaves orally, renal function parameters returned to normal ranges. Additionally, the urinary electrolytes were diluted, which may have contributed to a reduced risk of calculus formation. Histological analyses were consistent with the biochemical data. This study demonstrated that Cystone and ethanolic extracts of T. catappa leaves exhibited protective properties against urolithiasis induced by EG in rats. The higher dose of T. catappa extracts showed a more significant effect compared to the lower dose.

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

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

Cardiac Autonomic Modulation in Domestic Cats with Obstructive Lower Urinary Tract Disease.

Obstructive feline lower urinary tract disease (OFLUTD) is the most common complication of the urinary system, as metabolic and electrolyte changes can alter the functioning of the autonomic nervous system (ANS). The objective of this study was to describe the indices of heart rate variability (HRV) and their correlations with the observed alterations in Systolic Blood Pressure (SBP) and electrocardiographic, biochemical, and haemogasometric indices in cats diagnosed with OFLUTD. Sixty-five male cats up to 10 years of age were divided into two groups. The control group (CG) was composed of 25 healthy cats, and the obstructed group (OG) consisted of 40 cats with OFLUTD. The OG was evaluated by electrocardiography and blood pressure at four different time points. In the CG, electrocardiographic evaluation and SBP measurement were performed. A comparison of the HRV between the CG and OG (M0) revealed differences in the SDNN (standard deviation of all normal RR-NN) parameters (sympathetic and parasympathetic tone) and in the rMSSD (parasympathetic tone); there was a difference in the SBP, which was greater in the CG. There were higher rates in the CG. The HF and HR were greater in OG. The HRV serves as a preventive tool and predicts the severity of OFLUTD in patients due to an imbalance in the ANS.

Novel Biomarkers and Imaging Tests for AKI Diagnosis in Patients with Cancer.

The lack of non-invasive urine and blood-based biomarkers for the diagnosis of acute kidney injury (AKI) in patients with cancer is an area of significant unmet clinical need. Traditional non-invasive diagnostic tools that are currently utilized in the clinic, such as creatinine and cystatin C-based eGFR measurements, urinalysis, urine sediment exam, urine protein quantification, and urine electrolyte measurement, lack the sensitivity and specificity to distinguish between the various underlying etiologies of AKI in patients with cancer. Imaging-based diagnostics can be helpful to rule out urinary obstruction, but also lack sensitivity and specificity to diagnose the etiology of AKI. Kidney biopsy is often required for definitive diagnosis. As our scientific understanding of the biological pathways that are dysregulated in AKI has advanced, there has been considerable interest in developing new biomarkers for AKI. For example, the diagnosis of acute interstitial nephritis (AIN), which can occur in patients treated with immune checkpoint inhibitors (ICIs), promises to be revolutionized by the incorporation of urinary testing for inflammatory biomarkers such as C-X-C motif ligand 9 (CXCL9), tumor necrosis factor alpha (TNF-α), and interleukin 9 (IL-9). In the case of cisplatin administration, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) may improve prognostication, differentiating between persistent AKI resulting from acute tubular injury versus pre-renal azotemia. The development and validation of blood, urine and imaging biomarkers into widely utilized diagnostic tests will require a concerted effort, but could improve diagnosis, management and prognostication for a growing group of patients who are at high risk of developing AKI during the course of their illness.

Diuretic activity of ethanolic extract and fraction enriched in saponins from Solanum sisymbriifolium Lam. root in rats.

Solanum sisymbriifolium Lam. is a native perennial plant with chemical characteristics of therapeutic importance. In Paraguayan traditional medicine, it is attributed to antihypertensive and diuretic activities. For this reason, the objective of the study was to evaluate the effect of acute oral administration of the ethanolic extract and fraction enriched in saponins obtained from the root of S. sisymbriifolium on the diuresis profile of rats. Male Wistar rats were used, randomly distributed in 6 groups to evaluate the diuretic activity. The control group received distilled water; the diuretic group was treated with 20 mg/kg of furosemide. Two groups were treated with 50 and 100 mg/kg of the ethanolic extract of S. sisymbriifolium, and two other groups were treated with 1 and 10 mg/kg with the fraction enriched in saponins. The animals were placed in individual metabolic cages for a period of 24 h. Urine volume was determined at 5 and 24 h, and urinary electrolytes, pH, and glomerular filtration rate at 24 h. The findings indicated that both doses of the ethanolic extract and the saponin-enriched fraction significantly increased diuresis after 24 hours of treatment. Urinary pH was not affected. A significant increase in the urinary excretion of Na+ and Cl- was observed without affecting the elimination of K+ with both doses of the extracts. In addition, a significant increase in GFR was evidenced. Both ethanolic extract and saponins enriched fraction, presented natriuretic and saluretic effects with a possible mechanism of action mediated, at least partially, by the inhibition of carbonic anhydrase. Furthermore, it was possible to demonstrate the participation of the COX/PG pathway in the diuretic mechanism of the extracts in male rats.

The therapeutic potential of Ribes orientale in hypertension: Improving electrolyte balance, enhancing antioxidant activity, and modulating the muscarinic pathway

Cardiovascular diseases like hypertension require diuretics, but their effectiveness and side effects limit their use. Alternatives like Ribes orientale extract are being investigated for potential diuretic. In acute diuretic action, the extract and fractions of Ribes orientale were investigated in saline-loaded rats at doses of 12.5, 25, and 50mg/kg, p.o., while prolonged diuretic activity was also performed by administration of the most potent and significant dose of Ribes orientale butanol fraction (ROBF) for 7days. ROBF diuretic action was confirmed through parameters like urine volume, electrolyte concentration, pH and conductivity. The study found that 50mg/kg of ROBF had the most potent and significant diuretic activity, like furosemide (10mg/kg). It also produced significant natriuresis and insignificant kaliuresis in electrolyte excretion. ROBF increased diuretic activity significantly from the first and 7th days. In the mechanistic study, it has been evaluated that nitric oxide and prostaglandins pathways are not involved in the diuretic effect of ROBF, while cholinergic pathway might be responsible for the diuretic effect of ROBF. Hematological, renal function tests and histopathological studies confirmed the safety of Ribes orientale at 50mg/kg. Results showed slight changes in blood count parameters and no significant changes in creatinine and blood urea nitrogen levels compared to the negative control. Furthermore, downregulation of aldosterone by ROBF prolonged activity enhances the local bradykinin availability that results in marked diuretic and natriuretic activity. It is evident from the decreased level of malondialdehyde (MDA) that Ribes orientale reduces the oxidative stress while increased level of superoxide dismutase (SOD) depicts improving level of antioxidant activity. We conclude that the butanol fraction of Ribes orientale roots possesses a considerable diuretic effect. Therefore, more study is needed to identify the exact mechanism of action and the real efficacy of Ribes orientale as diuretic.

Effects of diluted seawater in drinking water on physiological responses, feeding, drinking patterns, and water balance in crossbred dairy goats

Background and Aim: In tropical regions, the intrusion of saline from seawater (SW) due to global warming and sea level rise in recent years is an important natural factor influencing goat well-being. This study aimed to determine the effects of diluted SW in drinking water on the physiological responses and eating and drinking patterns of crossbred dairy goats under tropical conditions. Materials and Methods: Twenty dairy goats were divided into four groups (five animals each) based on body weight and milk yield. Animals received either fresh drinking water (SW0.0, control) or diluted SW at concentrations of 0.5% (SW0.5, low salinity), 1% (SW1.0, moderate salinity), and 1.5% (SW1.5, high salinity). The experiment was performed for 49 days (1st–7th week). Throughout this period, daily food and water intake were measured every day. In addition, blood collection was performed on day 25. Total urine and feces were collected from days 25 to 29. Meal and drinking patterns were determined on days 31 and 32. Results: Salinity did not influence dry matter intake throughout the experiment (p > 0.05). However, SW had a significant effect on eating patterns. The effect of SW on water intake (WI) was pronounced from the 2nd to 7th weeks of this experiment (p < 0.05). The water balance decreased and plasma antidiuretic hormone levels increased from SW1.5 to SW2.5 compared to the other treatments. Rectal temperature and respiration rate increased from 15:00 to 17:00 in SW1.5 patients. The concentrations of plasma electrolyte, creatinine, and heat shock protein 70 did not differ between treatments (p > 0.05). The urinary excretion of Na+ from SW1.5 and K+ and Cl- from SW1.0 was higher than that from SW0.0 and SW0.5 (p < 0.01). Conclusion: Lactating crossbred goats adapted to low and moderate SW by increasing urine volume and urinary electrolyte excretion (Uex), whereas animals responded to high SW by either increasing Uex or altering drinking patterns to minimize salt stress. Keywords: antidiuretic hormone, dairy goat, kidney, saline water, water balance.

Urinary chloride excretion in critical illness and acute kidney injury: a paediatric hypothesis-generating cohort study post cardiopulmonary bypass surgery.

Renal chloride metabolism is currently poorly understood but may serve as both a diagnostic and a treatment approach for acute kidney injury. We investigated whether plasma chloride, ammonia and glutamine as well as urinary chloride, ammonium and glutamine concentrations may serve as markers for acute kidney injury in paediatric patients. We conducted a prospective observational trial in a tertiary care paediatric intensive care unit. Ninety-one patients after cardiopulmonary bypass surgery were enrolled. Plasma glutamine, creatinine, (serum) albumin, urinary electrolytes and glutamine were collected pre-cardiopulmonary bypass surgery, at paediatric intensive care unit admission, and at 6, 12, 24, 48 and 72 h after paediatric intensive care unit admission. The urinary strong ion difference was calculated. The median urinary chloride excretion decreased from 51 mmol/L pre-cardiopulmonary bypass to 25 mmol/L at paediatric intensive care unit admission, and increased from 24 h onwards. Patients with acute kidney injury had lower urinary chloride excretion than those without. The median urinary strong ion difference was 59 mmol/L pre-cardiopulmonary bypass, rose to 131 mmol/L at 24 h and fell to 20 mmol/L at 72 h. The plasma chloride rose from 105 mmol/L pre-cardiopulmonary bypass to a maximum of 109 mmol/L at 24 h. At 24 h the plasma chloride concentration was associated with the presence of acute kidney injury. There was no association between plasma or urinary amino acids and chloride excretion or kidney injury. In conclusion, renal chloride excretion decreased in all patients, although this decrease was more pronounced in patients with acute kidney injury. Our findings may reflect a response of the kidneys to critical illness, and acute kidney injury may make these changes more pronounced. Targeting chloride metabolism may offer treatment approaches to acute kidney injury.

Metabolic alkalosis treatment standard.

The kidney is poised to defend against development of metabolic alkalosis through non-adaptive mechanisms in the proximal nephron and adaptive processes in the distal nephron. Despite a prodigious capacity to excrete base, metabolic alkalosis is the most common acid-base disturbance in hospitalized patients. Development of this disorder requires pathophysiologic changes leading to generation of new HCO3- combined with an augmentation in the capacity of the kidney to reclaim filtered HCO3-. The initial approach to these patients is careful assessment of effective arterial blood volume focusing on the physical examination and urine electrolytes. Identifying the mechanisms by which the kidney's ability to correct alkalosis are perturbed provides an understanding of the clinical approach to differential diagnosis and appropriate treatment. While metabolic alkalosis is frequently not dangerous, in certain settings, metabolic alkalosis may contribute to mortality and should be aggressively managed.

Abstract P118: Effect of renal denervation on the blood pressure and progression of diabetic kidney disease in T2DN rats

Background: As a common complication of diabetes, diabetic kidney disease (DKD) is a chronic progressive disorder that can lead to kidney failure, and it is currently the leading cause of kidney replacement therapy in the USA and worldwide. Although renal denervation (RDNx) has recently been approved by the FDA to treat hypertension, contradictory findings have been reported on the effect of RDNx on the blood pressure and progression of DKD in type 2 diabetic mellitus. Here, we used type 2 diabetic nephropathy (T2DN) rats, a well-established non-obese model that displays similar renal abnormalities and hyperglycemic levels as seen in humans, to evaluate the effect of RNDx on the blood pressure and progression of DKD. Methods: Bilateral RDNx or sham surgeries were performed on male T2DN rats with mild and severe stages of DN (~20 or >35 weeks old). The blood pressure was monitored chronically using radio telemetry throughout the entire experiment. 24-hr urine collection, glucose tolerance test, and GFR measurement were performed at baseline and at the end of the experiments. Blood and urine electrolytes were measured using a blood gas analyzer. The amount of norepinephrine in the kidney was evaluated by ELISA. Results: Bilateral RNDx were successfully performed on T2DN rats with a significant reduction of norepinephrine in the kidneys of the RDNx group (244±13 vs. 8±1 pg/mg for >35 weeks old rats). The mean arterial pressure (MAP) and heart rate remain the same between the Sham and RDNx groups. The glucose tolerance test also indicates no difference between the two groups. While there is a significant decrease in the GFR in Sham group from baseline to week 3, the GFRs between Sham and RDNx groups are not different. Similarly, total body weight, kidney to total body weight ratio, heart to total body weight ratio, and blood and urine electrolytes are also not different between Sham and RDNx groups. Analysis of the younger group (~20 weeks old) is in progress. Conclusion: In summary, our data suggests that RDNx does not affect the blood pressure and progression of DKD in male T2ND rats, at least at the stage of severe kidney injury (>35 weeks old). Funding sources: National Institute of Health R01 DK135644 and R01 DK129227, Department of Veterans Affairs I01 BX004024 (to AS), and APS Postdoctoral fellowship (to BX).

Satisfactory 2-year outcome of minimal invasive hybrid stabilization with double treated screws for unstable osteoporotic spinal fractures

PurposeThis study evaluates whether the fracture level alters the outcomes of minimally invasive hybrid stabilization (MIHS) with double-threaded, uncemented polyaxial screws for unstable osteoporotic vertebral fractures.MethodsThis prospective cohort study included 73 patients (71.23% females, mean age: 79.9 ± 8.8 years) with unstable OF 3–4 fractures treated by MIHS between Nov 2015-Jan 2018. Patient characteristics, operative data, clinical outcomes, complications, radiological outcomes, and midterm (24-month) follow-up regarding functionality, pain, and quality of life were analyzed.ResultsPatients had thoracolumbar (71.23%), thoracic (10.97%), and lumbar (17.8%) fractures. Operative time was < 120 min in 73.97% of patients, with blood loss < 500 ml in 97.25% of cases. No in-hospital mortality was recorded. Spine-associated complications occurred in 15.07% of patients, while 36.98% of patients had urinary tract infections (n = 12), pneumonia (n = 5), and electrolyte disturbances (n = 9). The mean length of hospital stay was 13.38 ± 7.20 days. Clinically-relevant screw loosening occurred in 1.7% of screws, and secondary adjacent fractures were diagnosed in 5.48% of patients. The alpha-angle improved significantly postoperatively (mean change: 5.4°) and remained stable for 24 months. The beta-angle improved significantly from 16.3° ± 7.5 to 10.8° ± 5.6 postoperatively but increased slightly to 14.1° ± 6.2 at midterm follow-up. Although no differences were seen regarding baseline data, clinical outcomes, and complications, fracture level significantly altered the COMI score at 24 months with no effect on pain score or quality-of-life.ConclusionMIHS using polyaxial screws is a safe treatment for single-level osteoporotic spinal fractures. Fracture level did not alter radiological reduction loss; however, it significantly altered patients’ function at 24 months.

Long-Term Follow-up Results of Children with Urolithiasis Followed in Our Clinic

Title and Objective: Urolithiasis is a prevalent condition frequently observed in childhood within the Turkish population. The aim of this study was to evaluate the metabolic, radiological, and clinical features of pediatric patients with urolithiasis. Materials and Methods: Records of 158 children referred to the Pediatric Nephrology Department of Celal Bayar University between 2010 and 2020 with suspected urolithiasis and microlithiasis were retrospectively reviewed. The complaints and ages of the cases during hospital admission, their medical histories, and the location of the stones were determined. All patients underwent complete urine analysis, spot urine electrolytes, urine culture, serum electrolytes, kidney function tests, uric acid, albumin measurements, and urinary ultrasonography. 24-hour urine electrolytes were studied in patients capable of urine collection. Stone analysis using X-ray diffraction was performed on patients from whom stones were obtained. Results: Out of the individuals, 88 (55.7%) were male, and 70 (44.3%) were female, resulting in a male-to-female ratio of 1.25:1. The average age at the time of diagnosis was determined to be 89.82 ± 57.35 months. A family history of urolithiasis was reported in 108 (68.3%) patients, and 46 individuals (29%) were born from consanguineous marriages. At the time of diagnosis, 32 patients (20%) had a urinary tract infection. Stones were predominantly situated in the upper urinary system in 129 patients (81.6%), with 123 (77.8%) having unilateral stones and 35 (22.2%) having bilateral stones. Calcium oxalate stones were the most commonly observed (80%) in patients who underwent stone analysis. Hypercalciuria emerged as the most frequently identified urinary metabolic risk factor. At the end of the follow-up period, 14 patients experienced a recurrence, while 67 patients remained free of stones. Conclusion: Urolithiasis continues to be a significant concern among children in our nation. Due to the higher recurrence rate and more frequent underlying metabolic disorders in children with stone diseases compared to adults, metabolic assessment and stone analysis are recommended procedures, emphasizing the need for lifelong monitoring in these cases.

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.

Diuretic activity and urinary electrolyte effects of Hemidesmus indicus (L.) R.Br. &amp; Decalepis hamiltonii Wight &amp; Arn. in experimental rats

Introduction: Diuretic drugs are commonly prescribed as primary or adjuvant therapy in various diseases, including congestive cardiac failure and hypertension. However, the adverse effects limit their usage to specific populations. There is an excellent opportunity for drugs with effective diuretic action and limited side effects. The present research was designed to assess the diuretic potential of ethanolic extract of Hemidesmus indicus (HIEE) and Decalepis hamiltonii (DHEE). Methods: A total of 8 groups (n=6) of Wistar rats were used in the study to assess the diuretic activity of HIEE and DHEE. Group I was treated with 0.5% carboxymethyl cellulose (CMC), group II with furosemide (10 mg/kg, p.o), groups III-V with HIEE, and groups VI-VIII with DHEE, respectively, at 200, 400, and 800 mg/kg doses. After the treatment, animals were individually shifted to metabolic cages for urine collection at 5 and 24 h intervals and studied the urinary electrolytes. Saluretic and natriuretic effects and the index of HIEE and DHEE were calculated. Results: The results revealed that both extracts considerably (P &lt; 0.05) increased the urine volume and electrolytes (Na+ , K+ , Cl– ) compared to the normal control except low dose treatment. DHEE extract at 800 mg/kg dose showed higher diuretic potential than HIEE in the total volume of urine and urinary electrolytes (P &lt; 0.05). Conclusion: HIEE and DHEE possess diuretic potential, which should be confirmed in human studies.

Protective Role of Rosmarinic Acid in Experimental Urolithiasis: Understanding Its Impact on Renal Parameters.

This study aimed to assess the ability of rosmarinic acid (RA) to prevent kidney stone formation in an ethylene glycol and ammonium chloride (EG/AC) model. There was an increase in diuresis in the normotensive (NTRs) and hypertensive rats (SHRs) treated with hydrochlorothiazide (HCTZ) and exposed to EG/AC, while RA restored urine volume in NTRs. The EG/AC groups exhibited lower urine pH and electrolyte imbalance; these parameters were not affected by any of the treatments. Both HCTZ+EG/AC and RA+EG/AC reduced calcium oxalate crystal formation in NTR and SHR urine. Kidney tissue analysis revealed alterations in oxidative stress and inflammation parameters in all EG/AC-receiving groups, with RA enhancing antioxidant defenses in SHRs. Additionally, crystals were found in the kidney histology of all EG/AC-exposed groups, with reduced Bowman's capsule areas in NTRs and SHRs. The NTR VEH+EG/AC group showed intense renal damage, while the others maintained their structures, where treatments with HCTZ and RA were fundamental for kidney protection in the NTRs. Docking analysis showed that RA exhibited good binding affinity with matrix metalloproteinase-9, phosphoethanolamine cytidylyltransferase, and human glycolate oxidase enzymes. The data disclosed herein underscore the importance of further research to understand the underlying mechanisms better and validate the potential of RA for clinical use.

Dynamics of Urine Electrolytes in Term Neonates during the 1st Week of Life

Background: Urine electrolyte assessment is vital for diagnosing and managing neonatal conditions. However, the challenge of urine collection in neonates has resulted in a lack of standardized urine electrolyte reference values. Aim: This study seeks to explore the reference levels and potential trends in serum and urine electrolytes to better understand how the kidneys handle these substances. Methods: Healthy neonates were prospectively enrolled following normal births. Using biochemical methods, blood and urine samples were collected and analyzed on the 1st and 5th postnatal days. Statistical analysis was performed using descriptive statistics and the Wilcoxon matched-pairs signed-rank test. Results: This prospective study enrolled 55 healthy neonates. Significant changes in serum electrolyte concentrations were observed between the 1st and 5th days after birth. Notably, sodium, creatinine, urea nitrogen, and uric acid levels decreased, whereas potassium, calcium, and phosphate levels increased. Urine analysis revealed significant increases in the tubular maximum phosphate reabsorption per glomerular filtration rate and decreases in the fractional excretion of potassium and uric acid by Day 5. Conclusion: This study challenges prevailing assumptions about the stability of neonatal urine electrolytes and highlights dynamic changes in the first postnatal week. These insights lay the groundwork for further research into electrolyte disorders in newborns and have potential implications for improving neonatal care practices.

The Proximal Tubule Response to Low Potassium Is Mediated by mTOR/AKT Activation via Kir4.2

Background: The renal epithelium is highly sensitive to changes in blood potassium (K+) levels. We have a detailed understanding of distal K+-sensitive signaling pathways, yet proximal mechanisms are less well-defined. Results: Mice lacking the basolateral proximal tubule inwardly rectifying K+ channel, Kir4.2, (Kir4.2−/−) demonstrated normal blood and urine electrolytes at baseline. Upon removal of K+ from their diet, Kir4.2−/− animals decompensated as evidenced by increased urinary K+ excretion and development of a proximal renal tubular acidosis compared to control animals (Kir4.2+/+). Potassium wasting in Kir4.2−/− mice was not proximal in origin, but was dependent upon increased ENaC activity along the connecting segment. This was demonstrated by the correction of K+ wasting in knockouts treated with the ENaC inhibitor, amiloride. Using lithium clearance studies, we further demonstrated increased distal sodium delivery in Kir4.2−/− animals due to reduced proximal tubule sodium reabsorption. Optical clearing and three-dimensional confocal imaging reveal Kir4.2−/− mice failed to undergo proximal tubule hypertrophy when fed a low K+ diet, while the distal convoluted tubule response was exaggerated in knockouts compared to control animals. A phosphoproteomics mass spectrometry analysis identified increased mTOR/AKT signaling as mediating the proximal dietary response to K+ depletion in control animals, and changes to mTOR/AKT signaling was blunted in Kir4.2 knockouts. Lastly, we demonstrated in isolated renal tubules that AKT phosphorylation in response to low K+ depended upon mTORC2 activation by secondary reductions in intracellular Cl−. Conclusions: In this work we identify the basolateral inwardly rectifying K+ channel, Kir4.2, as a mediator of the proximal tubule response to K+ deficiency. Kir4.2 knockout mice increase their distal nephron transport burden to maintain electrolyte homeostasis in the face of deficient proximal tubule cell function. Data identify a conserved proximal role for cell Cl− which, as it does along the distal convoluted tubule, responds to extracellular K+ changes to activate intracellular kinase signaling. Along the proximal tubule, mTOR/AKT signaling is essential for the cell response to low K+. Proximal and distal nephron cell Cl− responses work in concert to preserve K+ homeostasis. These studies were supported by NIH grants DP5-OD033412 (AST), DK51265, DK95785, DK62794, DK7569, P30DK114809 (RCH, MZZ), and the Vanderbilt Center for Kidney Disease and Vanderbilt Diabetes Research and Training Center (DK020593) pilot and feasibility grant (JSD). 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.

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.