Study of Urinary Electrolytes and Fractional Excretion of Uric Acid in Evaluating Hyponatremia.

INTRODUCTION: Serum sodium levels <135 mmol/L are known as hyponatremia. The syndrome of inappropriate antidiuresis (SIAD), which is described by a drop in the effective arterial blood volume (EABV), is the most common cause of hyponatremia. This study was carried out to categorize hyponatremia based on volume status and on parameters like fractional excretion of uric acid (FE-UA), fractional excretion of sodium (FE-Na), urine uric acid (U-UA), and serum uric acid (SR-UA) values. MATERIALS AND METHODS: Sixty-one patients admitted to the Department of Medicine at Rajendra Institute of Medical Sciences (RIMS), Ranchi, with hyponatremia were included in the study by applying random sampling. Routine urine and blood samples were collected for biochemical tests. Institutional ethical clearance was obtained for this study. Data were analyzed using Statistical Package for the Social Sciences (SPSS) (version 21). Frequency, central tendency, receiver operating characteristic (ROC), and nonparametric Mann-Whitney U test analysis tools were utilized for analysis. RESULTS: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in nearly 50.82% of hyponatremic patients. Approximately, 70% of non-SIADH patients were hypovolemic. When compared to the non-SIADH group, patients in the SIADH group had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), lower pulse rates, and lower urine creatinine levels and urine creatinine to serum creatinine ratio. The non-SIADH group had significantly higher SR-UA levels (p < 0.0001), but the SIADH group had significantly higher U-UA levels and significantly lower SR-UA levels. Among the studied parameters, FE-UA was the most accurate in diagnosing SIADH. FE-UA (>12%) is a better diagnostic marker for distinguishing SIADH patients from non-SIADH patients. CONCLUSION: FE-uric acid was found to be the most superior in diagnosing SIADH, followed by FE-Na.

Adverse outcomes and mortality in individuals with eating disorder-related electrolyte abnormalities in Ontario, Canada: a population-based cohort study.

BACKGROUND: Individuals with eating disorders are at a higher risk of electrolyte abnormalities than the general population. We conducted the first representative cohort study assessing whether electrolyte abnormalities in people with eating disorders were associated with mortality and physical health outcomes. METHODS: This was a retrospective population-based cohort study in Ontario including people aged 13 years or older with an eating disorder and an outpatient electrolyte measure within 1 year (between Jan 1, 2008 and June 30, 2019). An electrolyte abnormality was any of hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, hypophosphataemia, metabolic acidosis, or metabolic alkalosis. The primary outcome was all-cause mortality. Secondary outcomes were hospitalisation, a cardiac event, infection, acute or chronic kidney disease, fracture, and bowel obstruction. In additional analyses, we examined a younger cohort (<25 years old) and individuals with no previously diagnosed secondary outcome. We involved people with related lived or family experience in the study. FINDINGS: 6163 patients with an eating disorder and an electrolyte measure within 1 year since diagnosis (mean age 26·8 years [SD 17·5]; 5456 [88·5%] female, 707 [11·5%] male; median follow-up 6·4 years [IQR 4-9]) were included. Ethnicity data were not available. The most common electrolyte abnormalities were hypokalaemia (994/1987 [50·0%]), hyponatraemia (752/1987 [37·8%]), and hypernatraemia (420/1987 [21·1%]). Overall, mortality occurred in 311/1987 (15·7%) of those with an electrolyte abnormality versus 234/4176 (5·6%) in those without (absolute risk difference 10·1%; adjusted hazard ratio 1·23 [95% CI 1·03-1·48]). Hospitalisation (1202/1987 [60·5%] vs 1979/4176 [47·4%]; 1·35 [1·25-1·46]), acute kidney injury (206/1987 [10·4%] vs 124/4176 [3%]; 1·91 [1·50-2·43]), chronic kidney disease (245/1987 [12·3%] vs 181/4176 [4·3%]; 1·44 [1·17-1·77]), bone fracture (140/1987 [7·0%] vs 167/4176 [4·0%]; 1·40 [1·10-1·78]), and bowel obstruction (72/1987 [3·6%] vs 57/4176 [1·4%]; 1·62 [1·12-2·35]) were associated with an electrolyte abnormality, but not infection or a cardiovascular event. Findings were consistent in young individuals (<25 years old) and those without secondary outcomes at baseline, by eating disorder type, and by sex. INTERPRETATION: Electrolyte abnormalities are associated with death and poor physical health outcomes, supporting the importance of monitoring and possible interventions to prevent adverse outcomes. Findings also call for a refinement of the definition of severity of eating disorder and replication of these findings in other jurisdictions. FUNDING: None.

Effects of donors' and recipients' preoperative serum sodium on the prognosis of liver transplantation.

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively.

Complex mechanism of brugada phenocopy: moderate hyponatremia and right ventricular compression by liver metastatic tumor - case report.

Brugada phenocopy (BrP) occurs in various clinical conditions and manifests as a Brugada-like ECG pattern with coved (type 1) or saddle-back (type 2) ST-segment elevation in the right precordial leads. Unlike Brugada syndrome (BrS), which is an inherited channelopathy, BrP is not associated with an increased risk of malignant arrhythmia. BrP has been reported in severe metabolic disturbances (significant hyponatremia, hypokalemia or hyperkalemia), mechanical heart compression, coronary artery disease, pulmonary embolism and myocarditis/pericarditis. The authors described a case of a 69-year-old female whose Brugada-like ECG was atypically associated with only moderate hyponatremia (127 mmol/l). She was admitted due to a skin and subcutaneous tissue infection of the left shank and coexistent urinary tract infection (without a fever). She had the history of advanced melanoma with multiple liver metastases. Her cardiac history was negative, especially the patient has never suffered from ventricular arrhythmias. ECG on admission showed saddle-back ST-segment elevation in the right precordial leads; however, the patient did not report any chest pain. Troponin I level and left ventricular function in echocardiography were normal while regional longitudinal strain in RV apex was decreased and showed post-systolic shortening. The substernal view revealed compression of the right ventricle (RV) by liver metastatic tumor. ECG changes disappeared quickly during natrium chloride supplementation and did not recur during hospitalization. This case illustrates that even moderate hyponatremia may be a reversible cause of BrP when other predisposing conditions (e.g. heart compression by tumor) coexist.

Intensive Care Management of Severe Hyponatraemia-An Observational Study.

Background and Subject: Hyponatraemia is a common electrolyte disorder. For patients with severe hyponatraemia, intensive care unit (ICU) admission may be required. This will enable close monitoring and allow safe management of sodium levels effectively. While severe hyponatraemia may be associated with significant symptoms, rapid overcorrection of hyponatraemia can lead to complications. We aimed to describe the management and outcomes of severe hyponatraemia in our ICU and identify risk factors for overcorrection. Materials and Methods: This was a retrospective single-centre cohort that included consecutive adults admitted to the ICU with serum sodium < 120 mmol/L between 1 January 2017 and 8 March 2023. Anonymised data were collected from electronic records. We included 181 patients (median age 67 years, 51% male). Results: Median admission serum sodium was 113 mmol/L (IQR: 108-117), with an average rate of improvement over the first 48 h of 10 mmol/L/day (IQR: 5-15 mmol/L). A total of 62 patients (34%) met the criteria for overcorrection at 48 h, and they were younger, presented with severe symptoms (seizures/arrythmias), and had lower admission sodium concentration. They were more likely to be treated with hypertonic saline infusions. Lower admission sodium was an independent risk factor for overcorrection within 48 h, whereas the presence of liver cirrhosis and fluid restriction was associated with normal correction. No difference was identified between the normal and overcorrected cohorts for ICU/hospital length of stay or mortality. Conclusions: In some patients with severe hyponatraemia, overcorrection is inevitable to avoid symptoms such as seizures and arrhythmias, and consequently, we highlight the key factors associated with overcorrection. Overall, we identified that overcorrection was common and concordant with the current literature.

Neuroinflammation-Induced SIADH in West Nile Virus Infection: An Uncommon Neurological and Endocrine Manifestation.

BACKGROUND West Nile virus (WNV) is a vector-borne flavivirus that is typically transmitted by Aedes and Anopheles mosquitos. WNV infection typically presents with symptoms consistent with viral meningitis, which include fever, headache, and meningeal signs. WNV infections are typically self-resolving, with symptoms lasting 3-10 days. Although uncommon, patients with WNV infection can be afflicted with hyponatremia, although the etiology is unclear. Because of encephalitis, neuroinflammation may be involved in the deterioration of adrenal signaling, leading to salt wasting. CASE REPORT We present the case of a 75-year-old man who presented with headache, neck pain, photophobia, and viral illness symptoms. He was found to be profoundly hyponatremic, concerning for SIADH. He had a sodium drop to 117 mmol/L, leading to further lethargy and confusion. He received 3% saline, fluid restriction, and salt tablets, and more common causes of SIADH were ruled out. MRI revealed the absence of the posterior pituitary bright spot. He was subsequently found to have positive WNV titers and improved with continued supportive treatment. CONCLUSIONS WNV presents a unique challenge to providers due to its difficult diagnosis and association with hyponatremia. There is no clear role for specific medical treatment such as corticosteroids vs IV immunoglobulins. Supportive care is recommended for those testing positive for WNV. Clinicians should consider the possibility of viral infections, such as WNV, in patients living in endemic areas who present with unexplained hyponatremia, cognitive symptoms, and relevant history.

Implications of Dysnatremia and Endocrine Disturbances in COVID-19 Patients.

Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin-angiotensin-aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients.

Prolonged extracellular low sodium concentrations and subsequent their rapid correction modulate nitric oxide production dependent on NFAT5 in microglia.

Hyponatremia is the most common clinical electrolyte disorder. Chronic hyponatremia has been recently reported to be associated with falls, fracture, osteoporosis, neurocognitive impairment, and mental manifestations. In the treatment of chronic hyponatremia, overly rapid correction of hyponatremia can cause osmotic demyelination syndrome (ODS), a central demyelinating disease that is also associated with neurological morbidity and mortality. Using a rat model, we have previously shown that microglia play a critical role in the pathogenesis of ODS. However, the direct effect of rapid correction of hyponatremia on microglia is unknown. Furthermore, the effect of chronic hyponatremia on microglia remains elusive. Using microglial cell lines BV-2 and 6-3, we show here that low extracellular sodium concentrations (36 mmol/L decrease; LS) suppress Nos2 mRNA expression and nitric oxide (NO) production of microglia. On rapid correction of low sodium concentrations, NO production was significantly increased in both cells, suggesting that acute correction of hyponatremia partly directly contributes to increased Nos2 mRNA expression and NO release in ODS pathophysiology. LS also suppressed expression and nuclear translocation of nuclear factor of activated T cells-5 (NFAT5), a transcription factor that regulates the expression of genes involved in osmotic stress. Furthermore, overexpression of NFAT5 significantly increased Nos2 mRNA expression and NO production in BV-2 cells. Expressions of Nos2 and Nfat5 mRNA were also modulated in microglia isolated from cerebral cortex in chronic hyponatremia model mice. These data indicate that LS modulates microglial NO production dependent on NFAT5 and suggest that microglia contribute to hyponatremia-induced neuronal dysfunctions.

Maintenance intravenous fluid therapy in infants with sepsis and hyponatremia: a clinical trial.

BACKGROUND: This study aimed to compare the effect of two methods of maintenance intravenous fluid therapy on hyponatremia in hospitalized infants with sepsis. METHODS: In a double-blinded randomized clinical trial, 60 term infants with sepsis were enrolled. Blood samples were taken to determine sodium, potassium, Creatinine, and BUN levels before the initiation of treatment. Urine samples were taken to assess specific gravity and urinary output. Infants in the intervention group received half saline in 10% dextrose and infants in the control group were assigned to receive the conventional solution as maintenance. The above indicators were re-evaluated 24 and 48 h after the initiation of treatment. Two groups were compared concerning the incidence of hyponatremia, and other criteria such as urinary output and urinary specific gravity, blood urea nitrogen (BUN), and creatinine levels. RESULTS: Hyponatremia was more common in the control group. Sodium levels were significantly higher in half saline recipients 24 h (137.83 ± 2.86 vs. 134.37 ± 1.91 mmol/L), and 48 h (138.10 ± 2.41 vs. 133.66 ± 1.98 mmol/L) after treatment (P < 0.001). Although BUN in the intervention group was significantly higher in comparison to the control group, the difference in urinary output, urine specific gravity, potassium, and Creatinine levels were not significant in the two groups. CONCLUSIONS: The use of a half-saline solution as maintenance fluid reduces the risk of hyponatremia after 48 h when compared to 0.18%NaCl. TRIAL REGISTRATION: This has been registered at Iranian Registry of Clinical Trials (Retrospectively registered, Registration date: 2017-10-12, identifier: IRCT2017053034223N1, https://irct.behdasht.gov.ir/trial/26204 ).

Electrolyte disorders related emergencies in children.

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes.Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

The association of hyponatremia and early postoperative complications in aseptic revision total shoulder arthroplasty.

PURPOSE: This study investigates the association between preoperative serum sodium levels and 30-day postoperative complications following aseptic revision total shoulder arthroplasty (TSA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent aseptic revision TSA from 2015 to 2022. The study population was divided into two groups based on preoperative serum sodium levels: eunatremia (135-144 mEq/L) and hyponatremia (< 135 mEq/L). Logistic regression analysis was performed to investigate the relationship between hyponatremia and early postoperative complications. RESULTS: Compared to eunatremia, hyponatremia was independently associated with a significantly greater likelihood of experiencing any complication (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.14-2.40; P = .008), blood transfusions (OR 2.45, 95% CI 1.24-4.83; P = .010), unplanned reoperation (OR 2.27, 95% CI 1.07-4.79; P = .032), and length of stay > 2 days (OR 1.63, 95% CI 1.09-2.45; P = .017). CONCLUSION: Hyponatremia was associated with a greater rate of early postoperative complications following noninfectious revision TSA. This study sheds light on the role of preoperative hyponatremia as a risk factor for postoperative complications and may help surgeons better select surgical candidates and improve surgical outcomes in the setting of revision TSA.

Hydroelectrolytic and nutritional needs of infants with epidermolysis bullosa during the first month of life.

Dehydration and malnutrition are common in infants with severe epidermolysis bullosa (EB), but their nutritional needs have been poorly studied. The principal aim was to assess the nutritional status, fluid and electrolyte balance, and nutritional intake of newborns with EB during the first month of life and estimate their needs during this period. This was a retrospective study over an eight-year period. Inclusion criteria were neonates with confirmed EB admitted to our neonatal referral unit during the first month of life. Exclusion criteria were hospitalisations <7 days. Twenty-seven patients with EB (mean [min-max] gestational age = 39 weeks [33; 41]; birth weight = 2986 g [1982; 4150]), were included. Four patients (15%) had hyponatraemia < 135 mmol/L at admission (age at admission = 4.8 days +/- 2.6 [2; 7]). Sixteen patients (59%) had a sodium deficit -requiring fluid and sodium intake well above recommendations from the World Health Organisation (WHO). The risk of hyponatraemia was significantly higher in infants with the greatest body surface area affected but did not appear to be related to EB subtype. Caloric and protein intake were well above the WHO's recommendations, preventing acquired growth restriction. The rate of sodium deficit in neonates with EB is high and related to the significance of skin exudate. The administration of nutrient intake greater than that recommended helps to prevent acquired growth restriction. We propose recommendations for nutritional intake and monitoring in neonates with EB in the first month of life.

Transient secondary pseudo-hypoaldosteronism in infants with urinary tract infections: systematic literature review.

Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases. CONCLUSIONS: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable. WHAT IS KNOWN: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection. WHAT IS NEW: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week.

Hyponatremia Is Associated with Mortality in Acute Pancreatitis Patients.

BACKGROUND: Disorders of serum sodium are common among general patients and are associated with poor outcomes. The prognostic value of serum sodium disorders in patients with acute pancreatitis (AP) has not been studied. We conducted this retrospective study to explore the association between serum sodium levels and the outcomes of patients with AP. MATERIALS AND METHODS: Patients with AP from the Medical Information Mart for Intensive Care III (MIMIC-III) were screened for this study. The laboratory variables, including serum sodium levels, were obtained by analyzing the first blood sample on the first day after admission. Univariate logistic regression was performed to discover potential factors for mortality of AP. The unadjusted and adjusted association between serum sodium level and mortality of AP was shown by the restricted cubic spline (RCS). The categorical cutoff for the detrimental effect of serum sodium level on the prognosis of AP was also confirmed by stepwise logistic regression after adjusting for con-founding effects of significant factors in the univariate logistic regression. RESULTS: A total of 869 patients with AP in the MIMIC-III were included with a mortality of 13.1%. Unadjusted logistic regression showed that age (p < 0.001), simplified acute physiological score (SAPS) (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), hemoglobin (p = 0.040), serum creatinine (p = 0.046), and serum phosphorus (p < 0.001) were significantly associated with the mortality of AP. The RCS showed that the serum sodium level was negatively and linearly associated with mortality of AP after adjusting for confounding effects of significant factors in the univariate logistic regression. Serum sodium < 133 mmol/L, which indicated hyponatremia, was significantly correlated with a higher mortality risk than serum sodium ≥ 133 mmol/L (p = 0.013). CONCLUSIONS: Hyponatremia is widely developed among patients with AP and correlates with a higher mortality risk of AP. Physicians should pay more attention to managing patients with AP with hyponatremia.

[Herpes simplex encephalitis complicated with cerebral salt wasting syndrome: a case study].

A 78-year-old man was admitted to the hospital with a 4-day history of fever and confusion. Physical examination revealed oral dryness and decreased skin turgor. Blood tests showed hyponatremia (121.5 |mEq/l), and cerebrospinal fluid examination revealed positivity for herpes simplex virus 1 (HSV-1) via polymerase chain reaction. He was diagnosed with herpes simplex encephalitis and initiated acyclovir treatment. The hyponatremia was diagnosed as cerebral salt wasting syndrome (CSWS) and treated with hypertonic saline infusion and fludrocortisone. The cerebrospinal fluid HSV-1 DNA became negative, and the serum sodium levels normalized. Hyponatremia complicated with encephalitis is often caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), whereas CSWS is rare, mostly observed in tuberculous meningitis. Differentiating between the SIADH and CSWS is important as they require distinct therapeutic strategies.

Association Between Preoperative Hyponatremia and Survival After Liver Transplant: A Systematic Review and Meta-Analysis.

OBJECTIVES: Numerous studies have been conducted to investigate the effects of preoperative hyponatremia on survival after liver transplantation. The variable findings underscore the necessity for performing a systematic review to elucidate the potential effects of preoperative hyponatremia. MATERIALS AND METHODS: We searched PubMed, Scopus, Web of Science, Science Direct, Cochrane Library, and reference lists of articles for observational cohort studies that reported association between preopera-tive hyponatremia and survival after liver transplant in adults regardless of publication year. We used the random-effect model to pool the extracted data for meta-analysis. RESULTS: Meta-analyses of mean difference in serum sodium levels showed that nonsurviving recipients had 2.58 mEq/L lower preoperative serum sodium levels than surviving recipients (0.02; 95% CI, .33-4.83). Two observational methods were used to assess survival after liver transplant of patients with preoperative hyponatremia. According to meta-analyses, no dif-ference in survival was shown between recipients with and without preoperative hyponatremia (sodium> 130 mEq/L) (≤1 month : 0.69 [95% CI, 0.9-1.07], 3-month survival: 0.54 [95% CI, 0.95-1.02]). Second, when we compared posttransplant survival of recipients with preoperative hypo-natremia versus those with normal serum sodium levels (sodium = 130-145 mEq/L), we found that recipients with preoperative hyponatremia had lower survival after liver transplant than those with normal preoperative serum sodium levels. CONCLUSIONS: Liver transplant recipients with preop-erative hyponatremia probably have shorter survival posttransplant than those with normal preoperative serum sodium level.

Vascular Calcification Is Accelerated by Hyponatremia and Low Osmolality.

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt (protein kinase B) pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

Efficacy of oral sodium chloride in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy: A randomized controlled trial (SCHO Trial).

INTRODUCTION: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia. MATERIALS AND METHODS: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared. RESULTS: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups. CONCLUSIONS: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388.

Risk factors and outcome of hyponatremia in patients with Guillain-Barré syndrome.

The objective of the present study was to evaluate the risk factors and outcomes associated with hyponatremia in patients with Guillain-Barré syndrome (GBS). We retrospectively studied 80 consecutive patients with GBS who visited our hospital and compared clinical, laboratory, and electrophysiological findings of patients with and without hyponatremia. Disability was evaluated using the Hughes grading system. Of the 80 patients, 18 (23%) had hyponatremia. Hyponatremia was significantly associated with older age (P = 0.003), urinary retention (P < 0.0001), Hughes grade ≥ 4 at admission and nadir (P = 0.003 and P < 0.001, respectively), acute inflammatory demyelinating polyneuropathy subtype (P = 0.017), sepsis (P = 0.001), mechanical ventilator support (P = 0.013), longer hospitalization length of stay (P < 0.0001), and inability to walk independently at 6 months (P < 0.001). Multivariate analysis performed to assess the risk factors of hyponatremia revealed that urinary retention (odds ratio [OR] 30.7, 95% confidence interval [CI] 3.6-264.4; P = 0.002) and mechanical ventilator support (OR 13.8, 95% CI 1.6-118.0; P = 0.017) were significant independent risk factors of hyponatremia. In assessing the outcomes of patients with hyponatremia, multivariate analysis showed that hyponatremia was independently associated with hospitalization length of stay ≥ 60 days and inability to walk independently at 6 month, with the former showing statistical significance but the latter not (OR 9.3, 95% CI 1.8-47.7; P = 0.007 and OR 4.9, 95% CI 0.9-26.3; P = 0.066, respectively). Therefore, we demonstrate that, along with mechanical ventilator support, urinary retention-possibly indicating autonomic dysfunction-is a risk factor of hyponatremia in GBS. Moreover, we confirm that hyponatremia is associated with poor outcome in GBS.