Apelin-13 Decreases Epithelial Sodium Channel (ENaC) Expression and Activity in Kidney Collecting Duct Cells

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APLNR (also known as APJ) are widely expressed within the central nervous system and peripheral organs including heart, lung and kidney. Several studies have shown that the apelin/APJ system is involved in various important physiological processes such as energy metabolism, cardiovascular functions and fluid homeostasis. In the kidney, the apelin/APJ system performs a wide range of activities. We recently demonstrated that apelin antagonises the hydro-osmotic effect of vasopressin on aquaporin-2 water channel (AQP-2) expression by reducing its mRNA and protein levels in collecting duct principal cells. The central role of these cells in water and sodium transport is governed by AQP-2 and the epithelial sodium channel (ENaC). The coordination of these channels is essential for the control of extracellular fluid volume, sodium homeostasis and blood pressure. This study aimed at investigating the role of apelin in the regulation of sodium balance in the distal nephron, and more specifically its involvement in modulating the expression and activity of ENaC in collecting duct principal cells. METHODS: mpkCCD cells were incubated in the presence of aldosterone and treated with or without apelin-13. Transepithelial Na+ current was measured and the changes in ENaC expression determined by RT-PCR and immunoblotting. RESULTS: Our data show that apelin-13 reduces the transepithelial sodium amiloride-sensitive current in collecting duct principal cells after 8h and 24h treatment. This effect was associated with a decrease in αENaC subunit expression and mediated through the ERK pathway as well as SGK1 and Nedd4-2. CONCLUSION: Our findings indicate that apelin is involved in the fine regulation of sodium balance in the renal collecting duct by opposing the effects of aldosterone, likely by activation of ENaC ubiquitination.

Clinical impact of personalized sodium prescriptions in hemodialysis

Dialysate sodium prescription is often standardized. In some patients, this can be hypernatremic compared to serum sodium, causing a positive sodium balance at the end of treatment that will contribute to increased extracellular volume and interdialytic weight gain. A prospective study was carried out to monitor and compare the clinical implications between different prescriptions of sodium dialysate (isonatremic versus hyponatremic hemodialysis). For that purpose, we included hemodialysis patients in treatment for at least 9 months. The individual sodium setpoint was determined through the median of pre-dialysis sodium measurements, carried out for 6 treatments. The prescribed dialysate sodium was equal to the setpoint (isonatremic period) for 4 weeks and then 2 meq/L inferior to the setpoint (hyponatremic period) for another 4 weeks. The main outcome was interdialytic weight gain. Secondary outcomes were ultrafiltration rate, blood pressure at the beginning of treatment, intradialytic complications, and qualitative assessment of symptoms. Twenty patients were included. Pre-dialysis serum sodium assessments in both periods tended to be patient specific with a stable value. The interdialytic weight gain was lower in the hyponatremic period (1.83±0.50 kg versus 2.04±0.58 kg) but without statistical significance (p value=0.387). The same trend was found in mean ultrafiltration and blood pressure. Dialysis complications were low in both periods. The percentage of cramps and hypotension requiring intervention was higher in the hyponatremic period with no statistically significant differences. Concerning thirst, there was a symptomatic improvement with sodium customization. This improvement was even more significant in the hyponatremic period. This study allowed us to reinforce the existence of a “sodium setpoint” for each patient and the importance of an individualized dialysis prescription. Our results suggest the safety of using isonatremic hemodialysis with improving patients’ symptoms. Regarding hyponatremic hemodialysis, despite being beneficial, it seemed to be associated with a higher number of complications.

Sodium Dialysate Prescription in a New Dialysis Facility

As the Medical Director of this new dialysis facility, I recommend a fixed sodium dialysate (Nadial) concentration at 138 mEq/L. This relates to my former experience in the Tassin unit in France and the fear of sodium as a powerful uremic toxin. I realize that, according to the Na+ set-point theory, a fixed value of the Nadial may create a plasma–dialysate (P–D) gradient and may favor intradialytic plasma Na+ changes. In cases where this is associated with signs of negative Na+ balance (bad session tolerance/quality of life) or positive Na+ balance (high interdialytic weight gain or high blood pressure), individualization of the Nadial to reduce the P–D gradient and change in plasma Na+ concentration may be useful, even though evidence remains scarce. I look forward to the possibility of using new dialysis machines that allow for the evaluation of sodium balance and tailoring of the sodium diffusion process.

Disorders of sodium balance in patients with hypothalamic-pituitary lesions in traumatic brain injury

Background. Traumatic brain injury (TBI) still remains the leading cause of death in people of working age. In Ukraine, the frequency of TBI varies from 2.3 to 6 cases (average of 4–4.2) per 1,000 population annually depending on the regions. Patients with primary damage to the brain and hypothalamic-pituitary system are at risk of developing cerebral edema due to the water-electrolyte imbalance and, accordingly, osmolar imbalance between cellular and extracellular spaces. Water-electrolyte imbalance as a result of damage to the hypothalamic-pituitary system in traumatic brain injury is not described enough in the literature. The functioning of the central and peripheral links of the endocrine system depending on the location, nature and severity of injury is examined not enough. The question of diagnostic and prognostic values of various indicators of volume status in patients with trauma is also underinvestigated. The purpose of this study was to examine the types of disorders of sodium balance in patients with isolated TBI and hypothalamic-pituitary lesions; to clarify the influence of sodium imbalance type on mortality in patients with TBI and hypothalamic-pituitary lesions. Material and methods. We examined 74 patients (men/women = 60/14) with focal cerebral contusion and lesions of the hypothalamic region. Forty-seven of them were diagnosed with hypovolemia combined with hyponatremia. Hypernatremia with hypervolemia was found in 15 patients. Intracranial pressure monitoring was performed using a multifunction monitor (BSM-3562, Japan, 2018, Nihon Kohden Corporation) with a line for invasive pressure measurement. Continuous non-invasive measurement of organ tissue oxygenation (rSO2) was carried out using Somanetics Invos Oximeter Cerebral/Somatic monitor (Covidien, Mansfield, MA, USA, 2020). Plasma electrolytes were evaluated in all patients. Conclusions. Patients with TBI and hypothalamic-pituitary lesion have different types of water-sodium imbalance, which demand the differentiated approach to their treatment. Given the small number of observations, we do not dare to link the type of sodium imbalance with lethality in patients with brain trauma and hypothalamic-pituitary lesions. We consider this requires further researches.

Total Body Sodium Balance in Chronic Kidney Disease

Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population.

The Effect of The Cucumber Consumption To The Level of Sodium Potassium in Mus Muscullus’s Urine Production

Cucumber (Cucumis sativus L.). was known for lowering blood pressure agents. Some researches show that Cucumber had a similar mechanism with a loop diuretic (Furosemide), exceeding sodium and potassium excretion. However, a part of Cucumber that gives a better effect on managing water and sodium balance remains unknown. This study was to explain the differences potential diuretic among parts of Cucumber (Cucumis sativus L.). This study was using a post-test only control group designed in animals. There were 44 male Mus musculus tested in this study. All of the animal testings was divided into 9 different treatment groups and 2 control groups. All Mus musculus got 1 mL methanol extract of Cucumber (Cucumis sativus L.) according to their group. The animal testing was put on metabolic cage to measure urine volume for 24 hours. The flesh and rind part of Cucumber (Cucumis sativus L.) showed a similar result with furosemide as diuretics agents. However, whole part of the fruit of Cucumber (Cucumis sativus L.) (flesh, rind, and seed) showed as natriuretic dan kaliuretic, Cucumber (Cucumis sativus L.) has a similar potential diuretic with Furosemide. Even in low concentrations of Cucumber extract, it led to having a potential diuretic, with natriuretic and kaliuretic effects in the whole part of the fruit. This could be suggested to people with chronic kidney diseases to prevent hyperkalemia.

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia

Objective: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on COVID-19-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact. Study design and methods: 117 patients (81 males, 64±13 years) hospitalized for COVID-19 between 1st March and 30th April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurements, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death. Results: At admission, 26.5% patients had hyponatremia, 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders (“mixed dysnatremia”). Lower sodium levels at admission were correlated with higher CRP (p=0.039) and serum lactate levels (p= 0.019), but not IL-6. Hypernatremia and a wider sodium variability were associated to maximum required ventilation, need of ICU assistance and duration of the hospitalization. Mean estimated time to ICU admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (Log-Rank test p=0.032). Conclusions: Sodium alterations frequently affect hospitalized COVID-19 patients. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients’ prognosis.