Prevalence and Prognostic Impact of Hyponatremia in Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis.

This study aims to systematically review the existing literature and perform a meta-analysis to evaluate the prevalence of hyponatremia among Guillain Barre Syndrome (GBS) patients and its relationship with disease prognosis. We comprehensively searched PubMed, Embase, Medline, Web of Science, Science Direct, and the Cochrane Library databases from 1995 to 2024 for observational studies on the prevalence of hyponatremia in GBS. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Heterogeneity among the included studies was calculated with the I2 for each analysis. We used the Comprehensive Meta-Analysis software (Version 3.3.070; Biostat, Englewood, USA). Eight observational studies met our inclusion criteria. The meta-analysis showed that the pooled prevalence of hyponatremia among GBS patients was 12% (95% CI: 0.107-0.149). The results exhibited high heterogeneity (I² = 99%), indicating significant variability among the studies. Hyponatremia rates reported in these eight studies ranged from 11.5% to 48% in GBS patients. The prevalence of hyponatremia was found to be 12% in GBS patients, which is relatively lower compared to some reports. Hyponatremia was found to be associated with prolonged hospital stay, mortality, and mechanical ventilation as poor prognostic factors. Further prospective studies are needed to elucidate the mechanisms underlying hyponatremia in GBS and to develop targeted interventions to address this issue.

Pseudohypoaldosteronism Type 1b in a Saudi Female Infant Due to Homozygous Variant Gene Mutation in SCNN1A: A Case Report.

Pseudohypoaldosteronism type 1 (PHA1) is a rare, heterogeneous group of disorders characterized by resistance to aldosterone action. We report the case of a 17-day-old Saudi female infant who presented on the third day of life with persistent hyperkalemia, hyponatremia, and metabolic acidosis. Initial evaluation for congenital adrenal hyperplasia was unremarkable. Genetic testing confirmed a novel homozygous variant (c.1522C>T p.(Arg508) chr 12:6458147 in SCNN1 A) in the SCNN1A gene, consistent with the diagnosis of PHA1B, a genetically confirmed subtype of PHA1. Prompt recognition and management of electrolyte disturbances are crucial in these neonates to prevent life-threatening complications.

Hyponatremia Among Elderly Hospitalized Patients: An Observational Study.

Aim The aim of this study is to analyze the demographic distribution (age and gender distribution), presenting symptoms, and evaluate the underlying etiology of hyponatremia among the study population. The presence of comorbidities and the volume status (hypovolemia, euvolemia, or hypervolemia) of elderly hyponatremic patients with varying severity of hyponatremia were assessed. Methods This cross-sectional, observational study was conducted in Dr. D. Y. Patil Hospital and Research Centre, Pune, India. After approval from the Institutional Ethics Sub-Committee (approval number: IESC/PGS/2022/09), it was conducted during the period between September 2022 and June 2024. The minimum sample size was calculated to be 96 with a confidence interval of 95% using WINIPEPI software (version 11.38). The lab values of serum sodium of all patients aged above 60 years admitted in wards and intensive care units (ICUs) were studied. Out of these hyponatremic patients, a sample size of 100 patients was randomly selected. Patients above 60 years and the patients who were on diuretic therapy were excluded from the study. Results The study included 100 elderly patients with a mean age of 73.25 ± 7.03 years, ranging from 64 to 86 years. Males predominated (63%), and severe hyponatremia (<125 mEq/L) was the most common, affecting 61% of patients. Generalized weakness (22%) and disorientation (17%) were the most frequently reported symptoms. Post-operative conditions (13%) and gastroenteritis (10%) were the leading causes. Most participants had no comorbidities (53%). Hypovolemia was present in 67% and euvolemia in 29% of the study subjects. Among hypovolemic patients, severe hyponatremia was present in 83.5% of patients. Conclusion This study highlights the significant burden of severe hyponatremia among elderly patients, particularly in male subjects and those with hypovolemia. Majority of the participants did not have any comorbidities. Additionally, the study emphasizes the need for heightened clinical vigilance in elderly patients presenting with generalized weakness and disorientation, as these were the most common symptoms associated with hyponatremia. The identification of post-operative conditions and gastroenteritis as leading causes further supports the need for comprehensive management strategies in elderly inpatients to prevent the occurrence and complications of hyponatremia.

Comparison of incidence of hyponatremia between linezolid and vancomycin in neonates and infants.

A previous study reported that the incidence of hyponatremia after linezolid (LZD) use was higher than that with vancomycin (VCM ) use in adults. However, hyponatremia due to LZD in neonates and infants was not investigated. This study aimed to compare the incidence of hyponatremia between LZD and VCM use in neonates and infants. The retrospective study was conducted at the Aichi Medical University Hospital. All patients who were cared for in NICU or GCU and received ≥ 3 days of LZD or VCM were included in this study. Hyponatremia was defined as serum sodium level ≤ 134 mEq/L and ≥ 5% decrease from baseline after administration of LZD or VCM. A total of 76 patients (LZD, N=36; VCM, N=37) were included. There was no significant difference in the incidence of hyponatremia between the two groups (19.4% vs 16.2%, p = 0.72). The proportion of patients with a minimum value of serum sodium ≤ 134 mEq/L during treatment was 47.3% in the LZD group and 35.1% in the VCM group (p = 0.29), and the decrease in serum sodium level from baseline to the minimum value was 80.5% and 78.4%, respectively (p = 0.85). In conclusion, there was no significant difference in the incidence of hyponatremia between the LZD and VCM groups. Therefore, it is not necessary to avoid LZD use in neonates and infants because of the risk of hyponatremia.

A Rare Presentation of Cryoglobulinemic Vasculitis Associated with Primary Sjögren's Syndrome.

INTRODUCTION: Sjögren's syndrome is a chronic autoimmune disorder that results in dry eyes and mouth. It is rarely associated with cryoglobulinemia, the agglutination of cryoglobulins at cold temperatures that leads to systemic inflammation and organ damage. We have, herein, presented a case of Cryoglobulinemic Vasculitis (CryoVas), which presents as cryoglobulinemic glomerulonephritis and Central Nervous System (CNS) vasculitis and peripheral neuropathy. CASE REPORT: A 52-year-old woman with a past medical history of Sjögren's syndrome was admitted to the intensive care unit with severe hyponatremia, orthopnea, and progressive lower extremity weakness, and was found to have an intradural extramedullary hematoma with mass effect in the thoracic spine and diffuse hyperintense cord signal abnormality in thoracic spine suggestive of intermixed proteinaceous or hemorrhagic material. Further testing demonstrated that the patient experienced worsening neuropathy, proteinuria, hematuria, declining renal function, and the presence of cryoglobulins in the blood. After a thorough examination and a renal biopsy, the patient was diagnosed with cryoglobulinemic glomerulonephritis and cryoglobulinemic vasculitis of the spine. The patient was treated with rituximab and pulse-dose steroids, with which the patient exhibited improved renal function and resolution of a previously seen intradural hematoma on repeat MRI. CONCLUSION: We have, herein, discussed a rare case of cryoglobulinemic vasculitis that has led to a rare CNS manifestation and concomitant cryoglobulinemic glomerulonephritis. This suggests that clinicians should consider cryoglobulinemic vasculitis as the etiology that could manifest with multiorgan involvement, especially in patients with underlying rheumatic diseases.

Adenosquamous carcinoma arising within a long-standing intrapulmonary bronchogenic cyst in an adult presenting with hyponatraemia.

A 74-year-old woman's persistent hyponatraemia led to the discovery of an adenosquamous carcinoma within an intrapulmonary bronchogenic cyst (IPBC), diagnosed 59 years prior. This is the first reported case of such a transformation in an IPBC. An adenosquamous carcinoma, originating from an intrapulmonary bronchogenic cyst identified 59 years prior, was discovered during the workup for a patient's unexplained, persistent hyponatraemia.

Risk Factors for Overly Rapid Correction in Patients with Profound Hyponatremia: A Retrospective Cohort Study.

Objective Overly rapid correction of profound hyponatremia can lead to osmotic demyelination syndrome; however, the incidence of and risk factors for overly rapid correction in patients with profound hyponatremia have not been thoroughly examined. Therefore, this study examined the incidence of and risk factors for overly rapid correction in patients with profound hyponatremia. Methods This single-center, retrospective cohort study conducted at an 865-bed teaching hospital analyzed data from 144 new inpatients with profound hyponatremia (initial serum sodium [Na+] level of <125 mEq/L) treated in our department between January 2014 and December 2022. Overly rapid correction was defined as serum Na+ correction of >10 mEq/L at 24 h. We examined the incidence of and risk factors for overly rapid correction.Results Thirty (20.8%) patients met the overly rapid correction criteria; however, none developed osmotic demyelination syndrome. A low initial serum Na+ level, female sex, primary polydipsia, and low frequency of follow-up in 24 h were significant independent risk factors for overly rapid correction in the multivariable analysis (p=0.020, p=0.011, p=0.014, and p=0.025, respectively). Conclusion Our study shows that a low initial serum Na+ level, female sex, primary polydipsia, and low frequency of follow-up within 24 h are associated with an increased risk for overly rapid correction of profound hyponatremia. Therefore, we suggest that physicians perform careful management when managing patients with profound hyponatremia with the risk factors for overly rapid correction identified in this study.

Unmeasured Osmoles: The Hidden Solutes Obscuring a Hyponatremia Evaluation.

Hyponatremia is defined as serum sodium less than 135 mEq/L and is principally a result of water excess relative to total body sodium content. The evaluation of hyponatremia is incomplete without a careful assessment of the patient's volume status, history, and acquisition of both serum and urine osmolality and sodium studies. Many of these studies can be affected by various clinical factors, and these nuances should be considered while interpreting the results. This is because these results guide the etiologic diagnosis of hyponatremia and consequently its management. In this report, we describe a 50-year-old male being evaluated for hyponatremia found to have unusual serum/urine osmolality studies but ultimately found to have an unmeasured serum osmole (ethanol) interfering with the interpretation of these results. Clinical scenarios that interfere with serum and urine studies commonly obtained in a hyponatremia evaluation are reviewed and an equation to correct for ethanol's osmotic contribution is described.

Continuous Kidney Replacement Therapy With Adjusted Dialysate Sodium Concentration for Severe Hyponatremia in Beer Potomania: A Case Report.

Beer potomania is a condition characterized by severe hyponatremia in chronic alcoholics with poor nutritional intake. When complicated by acute kidney injury (AKI), it presents a significant management challenge. We report a case of a 32-year-old male with a history of alcoholism who presented with malaise, nausea, and vomiting. Laboratory tests revealed severe hyponatremia (serum sodium 104 mEq/L) and AKI. Conventional treatment approaches posed risks of overcorrection and osmotic demyelination syndrome (ODS). We implemented continuous kidney replacement therapy (CKRT) with meticulously adjusted dialysate sodium concentrations. This approach enabled gradual, controlled correction of serum sodium without precipitating ODS. The patient was successfully liberated from hemodialysis on the twelfth day of illness. Our findings highlight the potential of CKRT as an effective treatment modality for severe hyponatremia in beer potomania with AKI, offering a means of gradual sodium correction while addressing renal dysfunction. This case underscores the importance of tailored management strategies in complex clinical scenarios involving electrolyte imbalances and kidney injury.

A Novel Steroidogenic Acute Regulatory Protein (StAR) Mutation Causing Adrenal Insufficiency in a Neonate: A Case Report of a Rare Medical Condition.

Congenital lipoid adrenal hyperplasia is a very rare and severe cause of adrenal insufficiency. It occurs due to a mutation of the steroidogenic acute regulatory protein (StAR), disrupting adrenal steroid biosynthesis. Here, we report a case of a three-week-old female infant with vomiting, failure to thrive, electrolyte imbalance, and generalized hyperpigmentation. The hormonal assay and genetic diagnosis confirmed a mutation in the StAR protein, leading to adrenal insufficiency. Appropriate replacement therapy resulted in the resolution of clinical and biochemical abnormalities. This case is being reported for its rare etiology and diagnostic clues. It can guide clinicians to keep adrenal insufficiency as a differential diagnosis in a neonate presenting with hyperpigmentation and electrolyte disturbance to save lives.

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.

Chronic Schizophrenia Presenting With Psychogenic Polydipsia Concealing Stage IV Uterine Adenocarcinoma: A Case Report.

Psychogenic polydipsia (PPD) may be commonly seen in patients suffering from schizophrenia. It remains unknown how often psychiatric illness can mask other more serious conditions. The patient is a 58-year-old female with chronic schizophrenia and PPD presenting to the emergency department (ED) with abdominal pain over a seven-year period from 2016 to 2022 with her symptoms attributed to a schizophrenia exacerbation with minimal to no diagnostic follow-up. After several ED admissions, in 2022, tumor marker tests were collected yielding concerning results for underlying cancer including CA125 85.9/50.1, CA19-9 >10, and CEA 0.3. A pelvic ultrasound was completed in 2022 after another three ED visits, revealing an infiltrative uterine mass measuring up to 5.6 cm, which was confirmed by CT abdomen and pelvis to be stage IV uterine adenocarcinoma. Several potential opportunities for intervention were missed in this patient including (1) primary prevention, (2) inadequate physical exam and history acquisition, and (3) delayed diagnostic imaging from the onset of abdominal pain to diagnosis. This case highlights the shortcomings across disciplines in providing early intervention and the disparities of basic patient care in psychiatric patients.

Predictive factors and scoring system for delayed symptomatic hyponatremia following endoscopic endonasal surgery: A single-center retrospective study.

BACKGROUNDS: Delayed symptomatic hyponatremia (DSH) is one of the common complications following endoscopic endonasal surgery (EES). Currently, published studies have predominantly focused on delayed postoperative hyponatremia, while there is relatively limited research on DSH. METHODS: We analyzed 175 consecutive cases from a single center between 2019 and 2023, involving patients who underwent endoscopic endonasal surgery (EES) for pituitary adenoma or Rathke's cleft cyst (RCC), all histopathologically confirmed. We collected preoperative, intraoperative, and postoperative data, and performed statistical analysis to determine the incidence of postoperative diabetes insipidus (DI) and identify significant predictive factors. Based on these factors, we developed a simplified scoring system. RESULTS: There were 29 cases (16.6%) of DSH occurrence. In the binary logistic regression analysis, Knosp grade ≥3 (OR, 4.19; 95% CI, 1.26-13.92; P=0.019), intraoperative cerebrospinal fluid leaks (OR, 3.93; 95% CI, 1.49-10.34; P=0.006), serum sodium on the second day after surgery (OR, 0.88; 95% CI, 0.78-1.00; P=0.049), and postoperative diabetes insipidus (OR, 2.88; 95% CI, 1.10-7.53; P=0.031) were factors with independent predictive value for DSH. The scoring system achieved a maximum area under the ROC curve (AUC) of 0.789 (95% CI, 0.697-0.881), with a cutoff value of 1, sensitivity of 86.2%, and specificity of 59.6%. CONCLUSION: The incidence rate of DSH after EES in patients was 16.8%. Knosp grade ≥3, intraoperative cerebrospinal fluid leaks, serum sodium concentration on the second day after surgery, and postoperative diabetes insipidus were associated with the occurrence of DSH.

Complexities of Severe Leptospirosis: A Case With Acute Hypoxic Respiratory Failure, Acute Kidney Injury, and Hyponatremia.

Leptospirosis, an acute zoonotic infection caused by spirochetes of the genus Leptospira, poses significant health risks worldwide. Transmission occurs through contact with infected animals' urine, blood, or tissue. This case report examines a 44-year-old man with severe leptospirosis, presenting as Weil's disease, characterized by acute hypoxic respiratory failure and acute kidney injury (AKI) secondary to rhabdomyolysis, complicated by severe hyponatremia. The case underscores the diagnostic and management challenges associated with leptospirosis, highlighting the importance of interdisciplinary collaboration and comprehensive diagnostic evaluation.

The Vasopressin Receptor Antagonist Tolvaptan Counteracts Tumor Growth in a Murine Xenograft Model of Small Cell Lung Cancer.

We have previously demonstrated that the vasopressin type 2 receptor (AVPR2) antagonist tolvaptan reduces cell proliferation and invasion and triggers apoptosis in different human cancer cell lines. To study this effect in vivo, a xenograft model of small cell lung cancer was developed in Fox1nu/nu nude mice through the subcutaneous inoculation of H69 cells, which express AVPR2. One group of mice (n = 5) was treated with tolvaptan for 60 days, whereas one group (n = 5) served as the control. A reduced growth was observed in the tolvaptan group in which the mean tumor volume was significantly smaller on day 60 compared to the control group. In the latter group, a significantly lower survival was observed. The analysis of excised tumors revealed that tolvaptan effectively inhibited the cAMP/PKA and PI3K/AKT signaling pathways. The expression of the proliferative marker proliferating cell nuclear antigen (PCNA) was significantly lower in tumors excised from tolvaptan-treated mice, whereas the expression levels of the apoptotic marker caspase-3 were higher than those in control animals. Furthermore, tumor vascularization was significantly lower in the tolvaptan group. Overall, these findings suggest that tolvaptan counteracts tumor progression in vivo and, if confirmed, might indicate a possible role of this molecule as an adjuvant in anticancer strategies.

Duloxetine-Induced Antidiuresis in Rats with Lithium-Induced Nephrogenic Diabetes Insipidus.

Antidepressants, including duloxetine, are a significant cause of drug-induced hyponatremia, which can disrupt the continuation of medication. Tolvaptan is beneficial for correcting hyponatremia caused by the syndrome of inappropriate antidiuresis, but its impact on duloxetine-induced hyponatremia remains unknown. We used male Sprague-Dawley rats to examine the impact of duloxetine treatment on lithium-induced nephrogenic diabetes insipidus (Li-NDI) and to evaluate whether the results were reversed by co-treatment with tolvaptan. To induce Li-NDI, lithium chloride (40 mmol lithium/kg dry food) was administered for 2 weeks. Duloxetine (50 mg/kg/day) and tolvaptan (10 mg/kg/day) were also administered in food to assess their individual effects over the same period. At the end of each animal experiment, kidneys were harvested to measure levels of cAMP, vasopressin-2 receptor (V2R), cAMP-responsive element binding protein 1 (CREB-1), aquaporin-2 (AQP2), and prostaglandin E2 (PGE2). Water diuresis was induced in the Li-NDI rats, and duloxetine treatment reduced polyuria while increasing urine osmolality. Duloxetine treatment prevented the decrease in total AQP2, AQP2 phosphorylation at serine 256, and CREB-1 phosphorylation in Li-NDI rats. The V2R mRNA level was also reduced in Li-NDI rats and restored by duloxetine treatment. In the subsequent experiment, the decreased water diuresis in Li-NDI rats treated with duloxetine was reversed by co-treatment with tolvaptan. Tolvaptan co-treatment also reversed the changes in AQP2 protein and CREB-1 phosphorylation in the renal cortex and medulla. The decreased cAMP levels in Li-NDI rat kidneys were elevated by duloxetine treatment, and this elevation was reversed by co-treatment with tolvaptan. However, the elevated PGE2 levels in Li-NDI rat kidneys were not affected by either duloxetine alone or tolvaptan co-treatment. In conclusion, antidiuresis was induced by duloxetine in Li-NDI and reversed by tolvaptan co-treatment through alterations in the V2R-cAMP-AQP2 pathway. These findings could underlie the mechanism of duloxetine-induced hyponatremia and suggest the potential usefulness of tolvaptan in treating drug-induced hyponatremia.

Adding Hyponatremia to the "Rule-of-6" Prediction Tool Improves Performance in Identifying Hospitalised Patients with COVID-19 at Risk of Adverse Clinical Outcomes.

The 'rule-of-6' prediction tool was shown to be able to identify COVID-19 patients at risk of adverse outcomes. During the pandemic, we frequently observed hyponatremia at presentation. We sought to evaluate if adding hyponatremia at presentation could improve the 'rule-of-6' prediction tool. We retrospectively analysed 1781 consecutive patients admitted to a single tertiary academic institution in Singapore with COVID-19 infection from February 2020 to October 2021. A total of 161 (9.0%) patients had hyponatremia. These patients were significantly older, with more co-morbidities and more likely to be admitted during the Delta wave (2021). They were more likely to have radiographic evidence of pneumonia (46.0% versus 13.0%, p < 0.001) and more adverse outcomes (25.5% vs. 4.1%, p < 0.001). Hyponatremia remained independently associated with adverse outcomes after adjusting for age, lack of medical co-morbidities, vaccination status, year of admission, CRP, LDH, and ferritin. The optimised cut-off for serum sodium in predicting adverse outcomes was approximately <135 mmol/L as determined by the Youden index. Although derived in early 2020, the 'rule-of-6' prediction tool continued to perform well in our later cohort (AUC: 0.72, 95%CI: 0.66-0.78). Adding hyponatremia to the 'rule-of-6' improved its performance (AUC: 0.76, 95%CI: 0.71-0.82). Patients with hyponatremia at presentation for COVID-19 had poorer outcomes even as new variants emerged.

Women have a higher risk of hospital admission associated with hyponatremia than men while using diuretics.

Background: Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia. Methods: All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level ≥135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125-134 mmol/L). Results: A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively). Conclusion: Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.

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.