Plasma Sodium Concentration Research Articles

Hyponatremia and risk of new-onset heart failure in patients with type 2 diabetes - a real-world study of 70,000 patients

Abstract Background Hyponatremia is common in patients with heart failure and in patients with type 2 diabetes (T2D), and is a risk marker for increased morbidity and mortality. However, it is unclear whether hyponatremia in patients with T2D is associated with an increased risk of new-onset heart failure. Purpose To investigate whether hyponatremia is associated with an increased risk of new-onset heart failure in patients with T2D. Methods From Danish nationwide registers, all patients with T2D with no history of heart failure were identified from 2013-2021. Patients with at least two samples of plasma sodium measured (at least one month apart), during the first six months following their T2D diagnosis, were included with follow-up start six months after T2D diagnosis as well. Patients were categorized in two groups according to the mean plasma sodium concentration at baseline: 1) sodium >137 mmol/L; and 2) sodium <137mmol/L. Cumulative incidence curves and Cox proportional hazards models (crude and adjusted for age, sex, comorbidities, and potential hyponatremia-inducing medications including diuretics, anticonvulsants, and antidepressants) were used to investigate the association of sodium concentration with the incidence of heart failure during follow-up. Incidence rates of heart failure per 1000 person-years were calculated across the spectrum of the measured sodium levels. Results We included 69,750 patients where 57% were male and the median age was 63 (interquartile range: 54-71). At index, 57,723 (83%) patients had a mean sodium concentration of >137 mmol/L and 12,027 (17%) patients had a mean sodium concentration <137 mmol/L (hyponatremia). Patients with a sodium level <137 mmol/L were associated with a significantly higher hazard rate of heart failure compared to patients with sodium concentrations >137 mmol: adjusted hazard ratio (HR) 1.27 (95% confidence interval 1.15-1.41, p-value <0.001). In analyses where sodium concentration was considered a continuous variable, increasing concentration of 1 mmol/L was associated with a decreasing hazard rate of heart failure: adjusted HR 0.96 (0.94-0.97, p-value <0.001). Conclusions Hyponatremia was common and associated with a significantly higher risk of new-onset heart failure in patients newly diagnosed with T2D. Whether hyponatremia could be a new treatment target to prevent heart failure in T2D remains to be determined.Cumulative incidence of heart failureIncident heart failure

Higher sodium in older individuals or after stroke/reperfusion, but not in migraine or Alzheimer’s disease – a study in different preclinical models

Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migraine model, a familial hemiplegic migraine type 2 (FHM2) mouse model, and a transgenic mouse model of Alzheimer’s disease (AD). Our results reveal that older rats exhibited higher sodium concentrations in cerebrospinal fluid (CSF), plasma, and various brain regions compared to their younger counterparts. Additionally, findings from the stroke model demonstrated a significant increase in sodium in the ischemic/reperfused region, accompanied by a decrease in potassium and an elevated sodium/potassium ratio. However, we did not detect significant changes in sodium in the NTG-induced rat migraine model or the FHM2 mouse model. Furthermore, AD transgenic mice showed no significant differences in sodium levels compared to wild-type mice in CSF, plasma, or the hippocampus. These results underscore the nuanced regulation of sodium homeostasis in various neurological conditions and aging, providing valuable insights into potential mechanisms underlying these alterations.

Associations of abnormal fluid status, plasma sodium disorders, and low dialysate sodium with mortality in hemodialysis patients.

Abnormal fluid and plasma sodium concentrations are established prognostic factors for hemodialysis patients. However, the cumulative effects of abnormal salt and water and potential effect modifications and the effect of dialysate sodium remain incompletely understood. The study followed 68,196 incident hemodialysis patients from 875 dialysis clinics in 25 countries over 10 years (2010-2020) investigating dose-response patterns between cumulative exposure time of fluid overload/depletion (measured by bioimpedance spectroscopy using the Fresenius Body Composition Monitor [BCM]), abnormal plasma sodium levels, low dialysate sodium, and all-cause mortality. We calculated time-varying cumulative exposure (in months) of relative fluid overload (any degree; >7% or severe; >13 or >15% in women or men, respectively) and fluid depletion (<-7%), hypo- or hypernatremia (sodium <135 or >145 mmol/L, respectively), low dialysate sodium (≤138 mmol/L), and estimated hazard ratios (HRs) for all-cause mortality using a multivariable Cox model. Of 2,123,957 patient-months, 61% were spent in any degree of fluid overload, 4% in fluid depletion, 11% in hyponatremia, and 1% in hypernatremia. Any degree of fluid overload was associated with higher all-cause mortality (HR peak at 3.42 (95% confidence intervals: 3.12-3.75) relative to no exposure), and this association with all-cause mortality appeared to be stronger with severe fluid overload. The risk pattern associated with hyponatremia was approximately linear in the first four patient-months and then plateaued after the fourth patient-month. We did not observe effect modification between fluid overload and hyponatremia. Even mild fluid overload was associated with higher mortality in hemodialysis patients. Whether a more stringent fluid management results in clinical improvement requires further investigation.

Edible mushroom (Pleurotus cornucopiae) extract vs. glibenclamide on alloxan induced diabetes: sub-acute in vivo study of Nrf2 expression and renal toxicity.

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.

Serial paired arterial and jugular venous point-of-care values in dogs undergoing manual basic life support.

To evaluate differences in point-of-care (POC) variables obtained from arterial and jugular venous blood in dogs undergoing manual basic life support (BLS) and report changes over time. Experimental study. Small animal research facility. Twenty-four purpose-bred research dogs. Dogs were anesthetized, and arterial catheters were placed before euthanasia. One minute after cardiopulmonary arrest, BLS consisting of manual chest compressions and ventilation delivered via endotracheal intubation, face mask, mouth-to-nose, or no ventilation was initiated. Paired arterial and jugular venous blood samples were obtained for POC testing before euthanasia (T0), at 3minutes (T3), and at 6minutes (T6) into BLS. The association of POC variables with arterial or venous sample type while controlling for type of ventilation and sampling timepoint was determined using a generalized linear mixed model. Variables obtained from arterial and venous blood samples were compared over time using repeated measures ANOVA or Friedman test. Pao2, anion gap, potassium, chloride, glucose concentration, and PCV were significantly higher in arterial blood samples compared with venous samples (P<0.03). By T6, arterial glucose concentration, arterial and venous base excess, venous pH, and plasma lactate, potassium, creatinine, bicarbonate, and sodium concentrations were significantly increased, and arterial and venous Po2, ionized calcium concentration, PCV, and total plasma protein concentration were significantly decreased from T0 (P<0.05). Although statistically significant, arteriovenous differences and changes in POC blood variables during BLS were small and not clinically relevant over time. Given the challenges of arterial blood sampling, it may be reasonable to pursue venous blood sampling during CPR. Further studies in dogs undergoing BLS and advanced life support are needed to better understand the potential clinical role of POC testing during CPR.

Correlation of plasmatic sodium determined by the laboratory and that determined by the dialysis machine

IntroductionChanges in plasma sodium concentration (pNa, expressed in mEq/L) are common in hemodialysis (HD) patients. Hemodialysis monitors can estimate pNa by using an internal algorithm based on ion dialysance measurements. The present study studies the accuracy of the correlation between the pNa estimated by the dialysis monitor and that measured by the biochemistry laboratory at our center. Material and methodsA single-centre prospective observational study in patients on a chronic HD program with the 6008 CAREsystem monitor and standard sodium (138mmol/L) and bicarbonate (32mmol/L) prescriptions. Venous blood samples were drawn from each patient before and after each HD session to ensure inter- and intra-individual validity. The pNa was measured in the biochemistry laboratory using indirect potentiometry and simultaneously the estimated pNa by the HD monitor was recorded at the beginning and at the end of the HD session. For statistical analysis, a scatterplot was made, and Spearman’s correlation quotient was calculated. In addition, the differences between both methods were represented as Bland-Altman diagrams. ResultsThe pre-dialysis pNa measured in the laboratory was 137.49±3.3, and that of the monitor, 137.96±2.91, with a correlation with R2 value of 0.683 (p<0.001). The post-dialysis pNa measured in the laboratory was 137.08±2.23, and that of the monitor was 138.87±1.88, with an R2 of 0.442 (p<0.001). On the Bland-Altman plots, the pre-dialysis pNa has a systematic error of 0.49, in favor of the monitor-estimated pNa, with a 95% confidence interval (CI) of (−3.24 to a 4.22). In the post-dialysis pNa, a systematic error of 1.79 with a 95% CI of (−1.64 to 5.22) was obtained. ConclusionThe correlation between the pNa estimated by Fresnius 6008 CAREsystem HD monitor and that measured by the laboratory is good, especially pre-dialysis measurements. Further studies should verify the external validity of these results.

#2707 Prediction of plasma sodium changes in hypernatremic patients: the role of tissue sodium content

Abstract Background and Aims Hypo- and hypernatremia are frequently encountered electrolyte disturbances in clinical practice. Rapid correction of these dysnatremias can result in severe neurological complications. Therefore, various formulas have been developed to predict changes in plasma sodium concentration ([Na+]) after treatment. However, these kidney-centered formulas have been shown to be inaccurate. A potential explanation for the discrepancy between predicted and measured plasma [Na+] is the accumulation of sodium in the skin, which is not explicitly taken into account in these formulas. The purpose of this post-hoc analysis is to evaluate the association between factors related to tissue sodium accumulation and the discrepancy between measured and predicted plasma [Na+]. Method We used data from a hypernatremic intensive care unit (ICU) cohort with 66 patients and 1,034 ICU days with complete data on sodium, potassium and water balance. We excluded ICU days with incomplete balances, dialysis and severe diarrhea. The predicted plasma [Na+] was calculated using the Barsoum-Levine (BL) and the Nguyen-Kurtz (NK) formula. Then, we calculated the discrepancy between predicted and measured plasma [Na+] (∆[Na+]). We fitted a linear mixed-effect model to investigate the association between factors related to tissue sodium content and ∆[Na+]. Age, sex, blood pressure, eGFR, CRP, plasma albumin, total body water (TBW), baseline plasma [Na+] and changes in plasma [Na+] were incorporated as fixed effects in the model, while the subjects were introduced as a random effect. TBW was estimated as 60% of body weight for males and 50% of body weight for females, corrected for fluid balances on subsequent ICU days. Results A total of 613 ICU days of 66 patients were included in our analysis. The mean age was 58 ± 15 years and 38% was female. The mean plasma [Na+] at inclusion day was 145 ± 9 mmol/L and mean eGFR CKD-EPI was 52 ± 28 ml/min/1.73 m2. On average, the deviation between predicted and measured plasma [Na+] was 3.8 ± 3.3 mmol/L for the BL formula and 3.9 ± 3.4 mmol/L for the NK formula. For both formulas, TBW (p = 0.01), baseline plasma [Na+] (p &amp;lt; 0.001) and plasma [Na+] change (p &amp;lt; 0.001) were significantly associated with the discrepancy between predicted and measured plasma [Na+] (Table 1). Plasma albumin (p = 0.02) was also significantly associated with this discrepancy when the NK formula was used. Conclusion In a hypernatremic ICU cohort, baseline plasma [Na+], estimated TBW and plasma [Na+] changes are associated with the inaccurateness of plasma [Na+] prediction. As baseline plasma [Na+] and estimated TBW are available when initiating treatment, incorporation of these variables in the currently available formulas may improve the prediction of plasma [Na+].

Evaluation of postoperative fluctuations in plasma sodium concentration and triphasic response after pediatric craniopharyngioma resection: A French cohort study.

Disturbances in plasma sodium levels are a major complication following recent resections of craniopharyngiomas in children. They must be properly managed to avoid neurological sequelae. We aimed to describe the variations and characteristics of postoperative natremia in children who had undergone a first craniopharyngioma resection with a particular focus on the frequency of triphasic syndrome in these patients. Paediatric patients with craniopharyngiomas who underwent a first surgical resection in the neurosurgery department of the Hôpital Femme Mère Enfant (Lyon, France) between January 2010 and September 2021 were included in the present study and the medical records were analysed retrospectively. A total of 26 patients were included. Of these, 17 (65.4%) had a postoperative course characterised by the occurrence of both initial diabetes insipidus (DI) and hyponatremia a few days later. Eight patients (30.8%) presented then with isolated and persistent DI. Patients with the triphasic syndrome had a significantly higher grade of Puget classification on MRI (1 and 2), compared to the other patients. Dysnatremia is common after craniopharyngioma resections in children. This immediate postoperative complication is particularly difficult to manage and requires rapid diagnosis and prompt initiation of medical treatment to minimize fluctuations in sodium levels and avoid neurological sequelae.

Diurnal rhythm of aquaporins expression and function in the kidney

Aquaporins (AQPs) are a protein family that plays a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and 3 (AQP3) are expressed on the collecting duct and regulated by the antidiuretic hormone, arginine vasopressin (AVP). AVP binds to its receptor on the collecting duct leading to increased expression of AQP2 on the apical membrane and AQP3 on the basolateral membrane to drive water reabsorption and promote urine concentration. We know that there are biological circadian rhythms that are critical for maintaining homeostasis. Therefore, we aimed to determine AQP2 and AQP3 expression and urine concentrating ability during their active time and inactive time in male and female mice. We hypothesize that there is a diurnal pattern in AQP2 and AQP3 expression or abundance leading to the variation of urine concentrating ability. Male (n=12) and female (n=12) C57BL/6J mice (10-11 weeks old) were euthanized in the middle of their active period (midnight) or the middle of their inactive period (noon). Spot urine osmolality was determined using a freezing point osmometer. Plasma sodium, chloride, and blood urea nitrogen (BUN) plasma concentration using an i-STAT blood analyzer. We localized aquaporins in kidney sections by using a diaminobenzidine chromagen method with antibodies against AQP2, AQP2 pS256 (an activation site), AQP2 pS261(an inhibitory site), and AQP3. Then, using a blinded method, the program Fiji Image J was used to quantify aquaporins on collecting ducts by using the integrated density (IntDen) parameter after calibrating into optical density (OD). We found that urine osmolality of control mice during their active period (2449±442.3 mOsm/ kg) was higher than that in the inactive time (1684±705.6 mOsm/kg, p = 0.0043). The plasma sodium concentration was higher in the active time (145±1.782 mmol/ L) than in the inactive time (142.9±1.311 mmol/L) with p = 0.0026. The plasma chloride (Cl−) and plasma BUN were also higher in the active time (Cl− = 115.2±1.4 mmol/L; BUN = 23±3.6 mmol/L) than in the inactive time mice (Cl− = 111±2.0 mmol/L, p &lt; 0.0001; BUN = 19.75±2.5 mmol/L, p = 0.0187). AQP2 was differentially expressed. During the active period, in both male and female mice, AQP2 was highly expressed in the collecting duct but was obviously reduced during the inactive period (active time = 4083±1006 OD; inactive time = 1243±608 OD, p &lt; 0.001). Moreover, AQP2 activation as determined by phosphorylation S256, was also greater during the active period (1148±404 OD) than inactive (221±96 OD, p = 0.002). Interestingly, the inhibitory site, phosphorylation of S261, was also greater during the active period (592 ± 378 OD) than the inactive period (162 ± 36 OD, p = 0.039). We found no significant difference in AQP3 localization or abundance. In summary, we showed that there is diurnal variability in urine osmolality (higher in their active period) that is supported by increased AQP2 expression during the active period of the mice, regardless of sex. Future studies will aim to determine if antagonizing and stimulating the vasopressin 2 receptor affects urine concentration in a diurnal manner. Intramural UAB funds to KAH. 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.

Dapagliflozin Stimulates Renal Ammonia Excretion in Rats

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs that induce glycosuria and are used to treat type 2 diabetes mellitus, moreover it has also been used in other conditions such as heart failure and atherosclerosis. However, little is known about the effects of these drugs on renal function. Considering that the maintenance of acid-base balance is closely related to renal physiology, in this study we evaluated the influence of chronic use of dapagliflozin on global renal function and urinary excretion of ammonia and titratable acids. Objective: To evaluate global renal function and urinary acid excretion (ammonia and titratable acid) in male Wistar rats chronically treated with dapagliflozin. Methods: 3-month-old male Wistar rats were randomized to control (C) and dapagliflozin (D) groups. Animals in group D received dapagliflozin (3 mg/kg, gavage) for 4 weeks. All animals were given food and water ad libitum throughout the experimental protocol. At 4 months of age, animals were placed in metabolic cages for 24-hour urine collection followed by blood sampling. Plasma concentrations of creatinine, sodium, potassium, urea, pH, pCO2, and bicarbonate were evaluated. The following were also evaluated: body weight, water intake, urine flow, and excretion of ammonia, titratable acids, glucose, and protein. Protocol approved by CEUA-UNIFESP number: 5985180423. Values expressed as mean ± standard error; number of animals per group: 6. Results: No significant changes were observed in blood gas parameters: pH (C: 7.33±0.043; D: 7.36±0.027), pCO2 (C: 53.30±2.40; D: 52.67±3.63 mmHg) and HCO3− (C: 27.07±1.31; D: 29.75±1.72 mEq/L) and no significant changes in plasma creatinine concentration (C: 0.41±0.04; D: 0.40±0.04mg/dl), Na+ (C: 144±0.47; D: 137±2.04 mmol/l) and K+ (C: 4.30±0.21; D: 4.16±0.20 mmol/l). We observed a significant increase in urine flow (C: 0.027±0.006; D: 0.068±0.005 mL/min/kg), possibly associated with intense glycosuria (C: 0.017±0.005; D: 8.97±0.51 g/24h). The significant increase in plasma urea concentration (C: 39.17±2.57; D: 48.83±1.27 mg/dL) and proteinuria (C: 11.04±0.30; D: 15.79±0.56 mg/24h) may indicate some renal impairment. Considering the marked increase in urinary excretion of ammonia (C: 0.65±0.05; D: 3.49±2.31 mEq/24h) and titratable acids (C: 0.180±0.036; D: 0.628±0.078 mEq/24h), we can conclude that the drug-induced glycosuria may lead to biochemical adaptations to maintain blood glucose levels within the normal range, at the expense of increased metabolic acid production. However, further experiments are needed to confirm this hypothesis. CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. 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.

Short-term effects of small volume saline infusion on acid base equilibrium in critically ill patients.

Short-term acid-base effects of 0.9% saline solution infusion are not well described. Aim of this study was to assess the effects of a fluid challenge with 0.9% saline in critically ill patients according to the Stewart's approach, which allows a precise determination of acid base equilibrium. In 40 mechanically ventilated critically ill patients, acid-base variables according to Stewart's approach were measured before and after 30 minutes from the infusion of 0.5L of 0.9% saline. Patients were divided in saline responder (fractional sodium excretion increase <0.5) and non-responders, and in patients with (estimated glomerular filtration rate >63 mL/min) and without renal impairment. After saline infusion, plasma sodium concentration did not change (138 [135-141] vs. 138 [135-140] mEq/L, P=0.646), while chloride concentration significantly increased (102 [100-106] vs. 104 [191-106] mEq/L, P=0.003), reducing strong ion difference (37.0 [34.9-38.0] vs. 35.4 [32.7-37.5] mEq/L, P=0.004) without any impact on pH, due to the concomitant albumin dilution. In saline non-responders, the increase of plasma chloride concentration caused a reduction in strong ion difference, while in saline responders both plasma chloride concentration and strong ion difference remained similar. Patients with and without renal impairment presented a similar acid-base response. The infusion of 0.9% saline reduced strong ion difference by increasing plasma chloride concentration, with no effect on pH due to concomitant albumin dilution. Saline non-responders, characterized by the ability to excrete the sodium excess, were more likely to suffer the acidifying effects of saline infusion, while renal function did not affect the acid-base response to saline infusion.

Long-term health outcomes associated with hydration status.

Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration - such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality - with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status.

Edelman Gamblegrams: a tool to teach and learn disorders of water/plasma tonicity homeostasis.

This article introduces an innovative teaching and learning tool called "Edelman Gamblegrams" that aims to help medical learners better understand disorders related to water/plasma tonicity homeostasis, i.e., hyponatremia and hypernatremia. Gamblegrams, named after physician James L. Gamble, are bar diagrams displaying the relative abundance of extracellular anions and cations and are commonly used in the analysis of acid-base disorders. The Edelman equation represents the physiological variables that determine plasma sodium concentration, namely, total body sodium mass, total body potassium mass, and total body water volume. Edelman Gamblegrams inspired by traditional Gamblegrams but using the components of the Edelman equation, visually demonstrate how sodium, potassium, and water contribute to plasma sodium concentration under normal and pathological conditions. Scenarios that lead to hypotonic hyponatremia and hypernatremia in Edelman Gamblegrams are also discussed. Furthermore, examples of how these visual aids can enhance understanding of the pathogenesis of dysnatremias are also presented. Overall, the use of Edelman Gamblegrams has the potential to improve comprehension and retention of concepts related to water/plasma tonicity homeostasis.NEW & NOTEWORTHY This article introduces a new teaching tool called "Edelman Gamblegrams," modeled after the conventional Gamblegrams used in acid-base disorder analysis and using the independent physiological variables that determine the plasma sodium concentration (Edelman equation), that aims to help medical learners understand disorders related to water/plasma tonicity homeostasis.

The Predictive Value of Plasma Sodium and Other Laboratory Parameters in Determining Complicating Appendicitis in Children

Objective: Finding a reliable preoperative predictor of complicated acute appendicitis (AA) has been a challenging diagnostic problem. The present study aimed to identify potential factors that may predict complicated AA in the pediatric emergency department (ED) based on routine, widely available laboratory tests on admission to the ED, including plasma sodium concentration. Methods: We retrospectively reviewed clinical and laboratory data of pediatric patients with AA who underwent emergency surgery at our department between January 2020 and December 2022. The patients were divided into two groups: histopathologically proven complicated AA (n = 80) and noncomplicated AA (n = 155). Results: Complicated AA was associated with reduced plasma sodium and chloride concentrations (p < 0.001, both), decreased values of lymphocytes (p = 0.002), elevated C-reactive protein (CRP) (p < 0.001), and elevated values of white blood cells (WBC) and neutrophils (p = 0.012 and 0.001, respectively). In binomial logistic regression, increased levels of CRP and WBC and decreased levels of sodium were predictors of complicated AA. The area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.764, 0.886). Conclusion: We identified mild hyponatremia and elevated CRP and WBC values as potential markers for distinguishing complicated from uncomplicated pediatric AA with implications for surgical approaches for treating complicated AA and conservative approaches for treating uncomplicated AA.

Forecasting individual exercise sweat losses from forecast air temperature and energy expenditure.

Recent success in predicting individual sweat losses from air temperature and energy expenditure measurements suggests a potential for forecasting individual sweat losses for future combinations of environment and exercise. The purpose of this study is to determine the plausibility of accurately forecasting exercise sweat losses from meteorological air temperature forecasts and individual running energy expenditure forecasts. The potential impact on plasma sodium is also estimated when setting drinking rates equal to forecast sweat losses. Individual exercise sweat losses (equated to water needs) and energy expended while running were measured in 33 participants along with air temperature and compared with forecasts of the same. Forecast inputs were used in a web app to forecast exercise sweat losses for comparison with observed values. The bias between forecast and observed exercise sweat losses was used to calculate the potential drinking impact on plasma sodium. The concordance correlation coefficient between forecast and observed values was 0.95, 0.96, and 0.91 for air temperature, energy expenditure, and exercise sweat losses, respectively, indicating excellent agreement and no significant differences observed via t-test. Perfect matching of water intake to sweat losses would lower plasma sodium concentrations from 140 to 138 mmol/L; calculations using the 95% limits of agreement for bias showed that drinking according to forecast exercise sweat losses would alter plasma sodium concentrations from 140 to between 136 and 141 mmol/L. The outcomes support the strong potential for accurately forecasting exercise sweat losses from commonly available meteorological air temperature forecasts and energy expenditure from forecast running distance.

Predictors of blood ionized calcium concentration in sick adult cattle.

Data on the factors affecting blood ionized calcium concentration (ciCa2+ ) and diagnostic performance of serum total calcium concentration (ctCa) measurements to detect abnormal blood iCa2+ status are lacking in sick adult cattle. Assess the association of ciCa2+ with venous blood pH, plasma concentrations of chloride (cCl), sodium (cNa), and potassium (cK), and ctCa, and total protein, albumin, and globulin concentrations in sick adult cattle. Two-hundred and sixty-five adult cattle (≥1-year-old) with different diseases. Prospective study. Whole blood pH, ciCa2+ , cNa, cK, and cCl were measured using a blood gas and electrolyte analyzer, whereas ctCa, and total protein, and albumin concentrations were determined using an autoanalyzer. The relationship between ciCa2+ and venous blood pH, plasma cCl, cNa, cK, and ctCa, and total protein, albumin, and globulin concentrations was investigated. Sensitivity and specificity were calculated for ctCa for diagnosis of abnormal ciCa2+ . Sensitivity of ctCa measurements to detect abnormal ciCa2+ was 66.0% whereas specificity of ctCa measurements was 72.3%. Serum total calcium concentration measurements accounted for 42% of adjusted blood ionized calcium (iCa2+ 7.40 ) concentration variance. Plasma cCl, and cK had explanatory power of ciCa2+ 7.40 , accounting for an additional 21% and 9% of the variance, respectively. Serum tCa measurements failed to accurately predict blood iCa2+ status in ill adult cattle. Serum tCa concentrations and plasma cCl were the strongest predictors of ciCa2+ in sick adult cattle.

Estradiol modulation of behavioral and physiological body fluid control during repeated dietary sodium deprivation

The low salt diet is a first line treatment for hypertension, but it is a difficult diet to maintain. As a result, patients may alternate between periods of high and low salt intake, the effects of which are unclear. Importantly, blood pressure increases in women after menopause, suggesting that estrogen plays a role in preventing hypertension. At present, however, it is unknown if the behavioral and physiological impact of alternating episodes on the low salt diet may be altered by the presence of estrogen. Our goals were to assess salt intake and body fluid hormones with repeated dietary sodium deprivations. Using ovariectomized rats with (EB) and without (OIL) estrogen treatment, we subjected rats to one or two dietary sodium deprivations using low salt laboratory chow. 0.5 M NaCl and water intakes were recorded after each period of regular chow or deprivation. After deprivation, rats were sacrificed, and trunk blood was collected for analysis of vasopressin, norepinephrine, epinephrine, and aldosterone levels. Plasma sodium concentration, plasma protein concentration, body weight, and uterine weight were also measured. There was no difference in the salt intakes of OIL- or EB-treated rats after one or two dietary sodium deprivations. However, EB-treated rats drank a less concentrated solution overall, suggesting less overcompensation after dietary sodium deprivation. Additionally, after a single episode of dietary sodium deprivation, EB-treated rats’ consumption remained elevated above baseline even after returning to regular laboratory chow. These behavioral differences were not explained by alterations in vasopressin, norepinephrine, epinephrine, or aldosterone. Plasma sodium and plasma protein concentrations also did not show alterations related to the change in behavior. Further research is necessary to determine the mechanism behind these changes in intake in EB-treated rats, which may ultimately be clinically relevant for both pre- and postmenopausal women on the low salt diet.

The Role of Sodium and Glucose in the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage: A Literature Review of New Evidence

AbstractThe present study aims to review the influence of glycemia and natremia on the propensity to develop complications, worse prognosis, and mortality risk in patients with aneurysmal subarachnoid hemorrhage (aSAH). This is an integrative literature review guided by the guiding question: “Do changes in blood glucose levels or plasma sodium concentration influence in-hospital morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage?”. The search for articles was performed on the PubMed platform, limiting the selection to works published in English in the period from 2017 to 2022. The results found demonstrate that the role of sodium ions in changes in the prognosis of patients is complex, with hypernatremia being the main factor described to worse outcomes. In contrast, the part of hyponatremia is controversial and may not have prognostic value, and serum sodium concentration is increasingly an important item to be evaluated in patients with aSAH. As for glucose, the variability of this substrate, both hyperglycemia and hypoglycemia, may be correlated with in-hospital and long-term mortality in patients with aSAH. Thus, the present study concludes that changes in blood glucose values and plasma sodium concentration influence the in-hospital morbidity and mortality of patients with aSAH. However, it is emphasized that the analysis of the independent influence of each of the related predictors must be done with caution due to the heterogeneity of the results found.

OR2805 Plasma Sodium Increase Is Associated With An Increase In Bone Formation In Outpatients With Chronic SIAD—A Predefined Secondary Analysis Of The SANDx Trial

Abstract Disclosure: S. Monnerat: None. J. Refardt: None. C. Meier: None. M. Christ-Crain: None. INTRODUCTION Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with increased mortality and morbidity, including an increased risk for osteoporosis and fragility fractures. Preclinical studies suggest that hyponatremia upregulates osteoclasts. In a previous analysis of 88 hospitalized patients with a syndrome of inappropriate antidiuresis (SIAD), we observed that hyponatremia normalization after 4 days had a positive impact on osteoblast function. METHODS This is a secondary analysis of a double-blind, crossover, placebo-controlled trial investigating the effect of 4-week treatment with empagliflozin 25mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). Two patients with an antiresorptive osteoporosis treatment and 1 patient with recent hip arthroplasty were excluded (n=11). The primary objective was to investigate the relationship between the change in bone formation index (BFI), defined as PINP/CTX, and the change in plasma sodium levels. Secondary objectives included the relationship between the change in the osteoblasts markers procollagen type 1 N (P1NP) and osteocalcin and the osteoclasts markers C-telopeptide crosslink (CTX), and the change in plasma sodium levels over the treatment period. Linear mixed models and Spearman correlation were computed. RESULTS Six out of the 11 outpatients with a chronic SIAD were female (median [IQR] age 73 years [66, 78]). At baseline, median [IQR] CTX concentration was 0.47 ug/L [0.29, 0.65], median [IQR] osteocalcin was 18.00 ug/L [13.95, 25.87] and median [IQR] P1NP was 64.64 ug/L [45.62, 68.45]. The calculated median BFI [IQR] was 131.86 [96.21, 168.73]. A sodium increase of 1 mmol/L was associated with an increase of 5.21 in BFI (95%-CI: 1.41, 9.00, p = 0.013) and with an increase of 1.48 ug/L in P1NP (95%-CI: 0.26, 2.62, p = 0.03). Plasma sodium concentration was not associated with a change in osteocalcin (β = 0.32; 95%-CI: -0.09, 0.72, p = 0.18), nor with a change in CTX (β = 0.003; 95%-CI: -0.008, 0.014, p = 0.324). Empagliflozin was not a significant predictor for the change of any bone markers and there was no interaction between treatment allocation and sodium. Changes in plasma sodium were positively correlated with changes in BFI and P1NP (BFI: ρ = 0.55, p &amp;lt; 0.001; P1NP: ρ = 0.45, p = 0.004) but not with CTX and osteocalcin (CTX: ρ = -0.21, p = 0.184; Osteocalcin: ρ = 0.34, p = 0.149). CONCLUSION An increase in plasma sodium levels in outpatients with chronic SIAD was associated with an increase in bone formation index (P1NP/CTX), which seemed to be triggered by an increase in P1NP, a surrogate marker of osteoblast function. This supports the importance of treating hyponatremia, particularly in older adults in whom chronic hyponatremia is also associated with falls. Presentation: Sunday, June 18, 2023

THU112 Effect Of Protein Supplementation On Plasma Sodium Levels And Urinary Urea Excretion In Patients With Chronic Siad—A Monocentric Open-Label Proof-Of-Concept Study—The Treasure Study

Abstract Disclosure: S. Monnerat: None. C. Atila: None. F.E. Baur: None. M. Dickenmann: None. M. Christ-Crain: None. INTRODUCTION The syndrome of inappropriate antidiuresis (SIAD) is the most common cause of euvolemic hyponatremia. Besides fluid restriction, increasing free-water clearance is an effective treatment approach that can be achieved through osmotic diuresis by administering oral urea. However, oral urea has a very peculiar taste that impedes long-term compliance. Dietary proteins are metabolized into soluble excretable urea by the liver. We hypothesized that dietary protein could increase free water clearance through urea-induced osmotic diuresis and therefore aimed to investigate the effect of high-protein supplementation on plasma sodium levels in outpatients with chronic SIAD. METHODS This is an interim analysis of a monocentric open-label proof-of-concept trial conducted at the University Hospital of Basel since October 2021. Adult outpatients with chronic SIAD of any etiology were eligible. Patients received 90g protein daily for 7 days in the form of protein powder dissolved in a maximum of 1L of liquid of choice. After a wash-out period of at least a week, patients received 30g of oral urea daily for 7 days. Patients were asked to keep their baseline fluid intake unchanged throughout the study. The primary endpoint was the increase in sodium levels from baseline to the end of the 7-day protein supplementation. RESULTS Thirteen patients, 10 females and 3 males, with chronic SIAD were included. Median [IQR] age was 63 [61, 80] and the median [IQR] duration of hyponatremia was 33 months [12, 42]. At baseline, median [IQR] plasma sodium concentration was 130 mmol/L [129, 133]. Eight patients had mild hyponatremia (130-134 mmol/L), 4 had moderate hyponatremia (125-129 mmol/L), and 1 patient had profound hyponatremia (&amp;lt;125 mmol/L). After 7 days of 90g daily protein supplementation (n = 13), sodium levels increased by a median [IQR] of 3 mmol/L [0, 5], blood urea nitrogen increased by a median [IQR] of 4.3 mmol/L [1.7, 5.1] and urinary urea corrected for urine creatinine increased by a median [IQR] of 26.0 mmol/mmol [17.1, 32.3]. After 7 days of oral urea (n = 8), sodium levels increased by a median [IQR] of 2 mmol/L [1, 3], blood urea nitrogen increased by a median [IQR] of 8.5 mmol/L [3.8, 10.2] and urinary urea corrected for urine creatinine increased by a median [IQR] of 31 mmol/mmol [21.1, 39.8]. CONCLUSION This interim analysis suggests that high-protein supplementation with protein powder increases plasma sodium levels in patients with chronic SIAD. The increase in urea concentration in both plasma and urine upon protein supplementation is comparable to the increase upon oral urea administration, which supports protein-induced ureagenesis to be the underlying mechanism of action. Presentation: Thursday, June 15, 2023