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Background and Aims Hyponatremia is associated with aggravation of inflammation in COVID-19 patients. However, to the best of our knowledge, no study has used longitudinal data and investigated the association between hyponatremia and COVID-19. Therefore, we analyzed COVID-19 patients’ changes in serum sodium (Na) levels from admission to discharge. Method We conducted a retrospective, single-center, observational cohort study, involving adult COVID-19 patients who were admitted to Japan Self-Defense Forces Central Hospital between April 1 and May 31, 2020. Serum Na level of < 135 mEq/L was defined as hyponatremia, 135–145 mEq/L as normonatremia, and > 145 mEq/L as hypernatremia. Inflammation was assessed by serum C-reactive protein (CRP) levels. Univariate logistic regression analyses were used to assess associations between hyponatremia at admission and need for oxygen or death during hospitalization. A comparison of serum Na levels at admission and discharge was tested using a paired t-test. Cross-sectional associations between serum Na and CRP levels at admission or days from onset to admission were analyzed using multivariate linear regression analyses. A restricted cubic spline (RCS) curve incorporated in one of these multivariate linear regression analyses was used to identify when serum Na levels were the lowest. In addition, we employed a mixed-effect model to examine the longitudinal association between changes in serum Na and CRP levels during hospitalization. Results Ninety-eight patients were enrolled, of whom 53 (54%) were male and 39 (40%) had a smoking history. Mean (SD) or median (IQR) of age, eGFR, body mass index (BMI), serum Na, and CRP at admission were 50 (17) years, 82 (20) mL/min/1.73m2, 23.3 (5.5), 138 (3.7) mEq/L, and 1.8 (0.2–6.0) mg/dL, respectively. It took an mean of 8.9 (3.7) days from onset to admission due to social disruption. According to government policies, during observation period, patients diagnosed with COVID-19 have to be hospitalized, even if they have minor or improving clinical symptoms. At admission, hyponatremia was observed in 11 (11.2%) patients; the rest of the patients had normonatremia. Twenty-seven (27.6%) patients received oxygen, and 4 (4.1%) died during hospitalization. Hyponatremia at admission was significantly associated with the need for oxygen (odds ratio: 41.2; 95% CI: 4.9–344; P=0.001) and death (odds ratio: 32.3; 95% CI: 3.0-347; P=0.004). Irrespective of hyponatremia at admission, the serum Na levels at discharge were significantly higher than those at admission (Fig. 1). In both cross-sectional and longitudinal analyses, serum Na levels were negatively associated with serum CRP levels after adjustment for age, sex, eGFR, BMI, and smoking history (P Conclusion Hyponatremia in COVID-19 may occur secondarily, and a condition called “COVID-19-induced hyponatremia” might exist.

Background and Aims Dysnatraemia is associated with increased mortality risk in the general population, but it is unclear to what extent kidney function influences this relationship. We investigated the impact of dysnatraemia on total and cardiovascular (CV) mortality while exploring the concurrent impact of chronic kidney disease. Method We utilised data from the Irish Kidney Disease Surveillance System (NKSS) to explore the association of serum sodium (Na+) (mmol/L) and mortality in a longitudinal cohort study. We identified all adult individuals (age > 18 years) who accessed health care from January 1st, 2007 and December 31st, 2013 in a regional health system with complete data on serum Na+, associated laboratory indicators and vital status up to 31st December 2013 (n = 32, 686). Patients receiving dialysis were excluded. The primary exposure was serum Na+ first recorded during the study period for each patient with a concurrent serum glucose measurement. Chronic kidney disease was defined as eGFR Results There were 5,118 deaths (15.7%) over a median follow up of 5.5 years. In multivariable adjusted models, the association of serum Na+ with all-cause and CV mortality followed a non-linear, u-shaped pattern. For all-cause mortality, the optimal range for greatest survival was between 139-146 mmol/L [HR 1.02 (1.00-1.03) and HR 1.19 (1.02-1.38) respectively, while for CV mortality, the optimal range was much narrower at 134-143mmol/L [HR 1.16 (1.02-1.23) and HR 1.09 (1.01-1.89) respectively] (Figure 1). The impact of serum Na+ on mortality was modified by baseline kidney function (p value < 0.001 for interaction). In stratified analysis, the impact of serum Na+ on all-cause mortality was greatly attenuated among patients with GFR< 60 ml/min/m², than above. This pattern was replicated in analyses of CV mortality. Conclusion This study supports the view that hypernatraemia and hyponatraemia are better tolerated with poorer kidney function. The risk thresholds for mortality were much narrower for CV death than all-cause death suggesting that these thresholds be taken into account to inform decision making and therapeutic interventions. Funding source Health Research Board (HRB-SDAP-2019-036), Midwest Research and Education Foundation (MKid)

Background Among laboratory abnormalities described in the context of SARS-COV-2 infection, hyponatremia seem to be the most common. The mechanism of this sodium disbalance is not well known. Aims Characterize the incidence, etiology and prognostic value of sodium disbalance in patients with COVID19. Method Observational pilot study with 37 patients admitted to Hospital Ramon y Cajal in Madrid, Spain, between March and April 2020, with a confirmed diagnosis of COVID19. Patients were followed until discharge or death. Clinical and laboratory data were collected at admission and before the clinical outcome. Variables were analyzed comparing hyponatremic vs eunatremic patients. Results Distribution of patients according to their serum sodium was as follows: 16 patients with hyponatremia (44%), 19 with normal serum sodium (51%) and 2 with hypernatremia (5%). The average sodium level in hyponatremic patients was 130 ±3.2 mmol/l, median urine sodium was 36 ±3.2 mmol/l (only 6 urine sample available). Hyponatremia was associated with dyspnea at admission and with higher levels of LDH, neutrophil cells account and C reactive protein. However, no worse prognostic was associated with lower serum sodium. All patients recover sodium levels at discharge treated with salt supplementation and free water intake. Conclusion mild hyponatremia is a common electrolyte disorder associated with COVID19. Sing as low urine sodium and recover with water and salt ingestion, point toward hydrosaline dehydration instead of SIADH as most common origin of hyponatremia.

Background and Aims Crystalline solutions, such as normal saline 0.9% (N/S 0.9%) and Ringer's Lactate (L/R), are readily administered for increasing plasma volume. Despite the utility of administering N/S 0.9% to hypovolemic patients, the dose of 154 mmol of sodium (Na) contained in 1 L exceeds the recommended daily dose increasing the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R solution has the advantage of lower Na content, significantly less chlorine and contains lactates which may be advantageous in patients with significant acidemia such as patients with acute kidney injury (AKI) and chronic kidney disease (CKD). The aim of the present study is to investigate the safety and efficacy of administration of L/R versus N/S 0.9% in patients with prerenal AKI and established CKD. Method The study included adult patients with known CKD stage II to V without need for dialysis, with prerenal AKI (AKIN Stage I to III Criteria). Patients with other forms of AKI as well as hypervolemia, heart congestion or hyperkalemia (serum K>5.5 meq/l) were excluded from the study. Patients were randomized in 1:1 ratio to receive intravenously either N/S 0.9% or L/R solution at a dose of 20 ml/kg body weight/day. We studied kidney function (eGFR: CKD-EPI) and response to treatment at discharge and at 30 days after discharge, duration of hospitalization, improvement in serum bicarbonate levels (HCO3), acid-base balance, serum potassium levels and the need for dialysis. Results The study included 26 patients (17 males) with a mean age of 59.1 ± 16.1 years. Thirteen patients received treatment with N/S 0.9% and the rest with L/R solution. Baseline demographic and clinical characteristics at hospital admission and historical data did not show any significant differences in both groups of patients. Renal function at the onset of AKI did not show significant differences between the two groups (16.4 ± 5.8 vs 16.9 ± 5.7 ml/min/1.73 m2, p=ns, treatment with N/S and L/R respectively). The mean volume of solutions received by the two groups (N/S 0.9% 1119 ± 374 vs L/R 1338 ± 364 ml/day, p=ns) as well as the mean total volume of liquids received per day, did not differ significantly (2888 ± 821 vs 3069 ± 728 ml/d, p=ns). Patients treated with L/R were discharged 1 day earlier than patients treated with N/S (5.2 ± 3.2 vs 6.2 ± 4.9 days of hospitalization, p=ns). Renal function improvement during hospitalization and 30 days after discharge did not differ significantly between the two groups. Patients that received L/R showed a higher increase in plasma HCO3 (ΔHCO3) concentration at discharge than those that received N/S 0.9% (4.9 ± 4.1 vs 2.46 ± 3.7 meq/l, p=ns) and pH increase (ΔpH) was slightly higher in those that received L/R solution (0.052 ± 0.066 vs 0.023 ± 0.071, p=ns). Patients treated with N/S 0.9% showed a greater decrease in serum potassium (ΔK) at discharge compared to those treated with L/R (-0.39 ± 1.03 vs -0.17 ± 0.43 meq/l, p=ns, respectively). No patient received acute dialysis treatment. Conclusion Administration of L/R solution as a hydration treatment to patients with prerenal AKI and established CKD is not inferior concerning safety and efficacy to N/S 0.9% solution. In addition, L/R administration seems to marginally improve acid-base balance in this specific group of patients.

Background and Aims It is traditionally believed that high consumption of sodium chloride leads to the development of arterial hypertension, which, in turn, will cause heart remodeling. However, more and more evidence is accumulating that a high sodium chloride content in the diet can cause heart damage without increasing blood pressure (BP). This is confirmed in experiments on rats. In addition, in animals of this species, supplementing a high-salt diet with soy proteins can prevent cardiovascular damage. Whether such mechanisms operate in primates remains unclear. Method The study was performed on male Macacus fascicularis. Monkeys were included in the experiment at the age of 4.6 -7.0 years and had a body weight of 5,5-7,5kg. Animals were divided into 3 groups. The first (control) included 5 animals, received standard ration; the second – 5 animals, received diet with high sodium chloride content (8 g NaCl/1 kg of the feed); the third – 6 animals, who were on a diet with high salt contents supplemented by soya isolated proteins (200 g/kg of the feed). In anesthetized animals measured blood pressure and performed an echocardiographic investigation. Follow up period lasted four month. Results Initially, in all groups of animals, blood pressure levels (Mean(SEM)) and echocardiographic parameters did not significantly differ. During the observation period, the studied parameters did not change much. For example, in the first group, an ejection fraction (EF) increased from 61.7(1.67) to 71.6(4.74), %; P=0.045. In the same group, a tendency toward a decrease in the left ventricle end-systolic dimension (1.50(0.056)vs 1.29(0.118), mm; P=0.079) was noted. Whereas the level of systolic and diastolic blood pressures in this group (for example, systolic BP: 115.4(3.95)vs 126.0(5.39), mm Hg; P=0.134) as well as in other groups of monkeys did not change significantly. Nevertheless, after four months of observation, the level of systolic blood pressure in the second group (126.0(5.39) mm Hg) of animals was significantly higher than in the first (103.0(5.54), P=0.0118) and nonsignificantly - in the third (104.0(8.39), mm Hg; P=0.065). EF in the end of follow up period in second group (71.6(4.74%) was significantly higher than in control (58.1(2.72),%; P=0.039) but not in the third group (60.9(5.03),%; P=0.162). Tricuspid annular plane systolic excursion in second group (1.02(0.08), mm) had an insignificant tendency to increase in comparison to the first (0.782(0.096), mm; P=0.094) or third (0.818(0.049), mm; P=0.052) groups. Conclusion Our data do not exclude the possibility that a high salt content in the food of lower primates can contribute to an increase in blood pressure and a change in heart function. However, to resolve the issues of the relationship between changes in heart function and the level of blood pressure and the presence of the cardioprotective effect of soy proteins under these conditions, longer observations are needed.

Author(s): Rhee, Connie M; Ravel, Vanessa A; Ayus, Juan Carlos; Sim, John J; Streja, Elani; Mehrotra, Rajnish; Amin, Alpesh N; Nguyen, Danh V; Brunelli, Steven M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundA consistent association between low serum sodium measured at a single-point-in-time (baseline sodium) and higher mortality has been observed in hemodialysis patients. We hypothesized that both low and high time-varying sodium levels (sodium levels updated at quarterly intervals as a proxy of short-term exposure) are independently associated with higher death risk in hemodialysis patients.MethodsWe examined the association of baseline and time-varying pre-dialysis serum sodium levels with all-cause mortality among adult incident hemodialysis patients receiving care from a large national dialysis organization during January 2007-December 2011. Hazard ratios were estimated using multivariable Cox models accounting for case-mix+laboratory covariates and incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose.ResultsAmong 27 180 patients, a total of 7562 deaths were observed during 46 194 patient-years of follow-up. Median (IQR) at-risk time was 1.4 (0.6, 2.5) years. In baseline analyses adjusted for case-mix+laboratory results, sodium levels l138 mEq/L were associated with incrementally higher mortality risk, while the association of sodium levels ≥140 mEq/L with lower mortality reached statistical significance only for the highest level of pre-dialysis sodium (reference: 138-l140 mEq/L). In time-varying analyses, we observed a U-shaped association between sodium and mortality such that sodium levels l138 and ≥144 mEq/L were associated with higher mortality risk. Similar patterns were observed in models incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose.ConclusionsWe observed a U-shaped association of time-varying pre-dialysis serum sodium and all-cause mortality in hemodialysis patients, suggesting that both hypo- and hypernatremia carry short-term risk in this population.

stable in 5% of cases, worst in 43% of cases. Conclusions: Our study confirms that hypernatremia is a situation known in less than 1% of patients admitted to the emergency department. It mostly happens with old patients, with cognitive disorders, and generally it is associated with extracellular dehydration. Most of the times, the admission’s reason to the emergency is confused with the cause of hypernatremia. The mortality of hypernatremic patients is important because of underlying comorbidities and the reason for admission to the emergency. After one day of hospitalization, 43% of patients have serum sodium higher than at the entrance. The factors which increase the natremia are numerous: inadequate choice for the rehydration fluid, no calculation of water deficit, less prescription by prescriber (rate). Hypernatremia is a situation related with a significant mortality. The emergency management of hypernatremia has to be improved. Several factors lead to the aggravation of the hypernatremia during the first 24 hours for some patients.

Background. Our objective was to study the risk factors and mechanisms of hypernatraemia in critically ill patients, a common and potentially serious problem. Methods. In 2005, all patients admitted to the medical, surgical or neurological intensive care unit (ICU) of a university hospital were reviewed. A 1:2 matched case-control study was performed, defining cases as patients who developed a serum sodium >= 150 mmol/l in the ICU. Results. One hundred and thirty cases with ICU-acquired hypernatraemia (141 +/- 3 to 156 +/- 6 mmol/l) were compared to 260 controls. Sepsis (9% versus 2%), hypokalaemia (53% versus 34%), renal dysfunction (53% versus 13%), hypoalbuminaemia (91% versus 55%), the use of mannitol (10% versus 1%) and use of sodium bicarbonate (23% versus 0.4%) were more common in cases (P < 0.05 for all) and were independently associated with hypernatraemia. During the development of hypernatraemia, fluid balance was negative in 80 cases (-31 +/- 2 ml/kg/day), but positive in 50 cases (72 +/- 3 ml/kg/day). Cases with a positive fluid balance received more sodium plus potassium (148 +/- 2 versus 133 +/- 3 mmol/l, P < 0.001). On average, cases were polyuric (40 +/- 5 ml/kg). Mortality was higher in cases (48% versus 10%, P < 0.001), for which hypernatraemia was an independent predictor (odds ratio 4.3, 95% confidence interval 2.5 to 7.2). Conclusions. Hypernatraemia seems to develop in the ICU because various factors promote renal water loss, which is then corrected with too little water or overcorrected with relatively hypertonic fluids. Therapy should therefore rely on adding electrolyte-free water and/or creating a negative sodium balance. Adjustments in intravenous fluid regimens may prevent hypernatraemia.

Patients with chronic renal failure on periodical dialysis frequently are hypertensive. This frequency has increased in relation to the liberalization of diet and to short dialysis with a high sodium concentration in the dialysate. Although various factors influence the pathogenesis of this type of hypertension, volume overload is the most significant. The achievement of an optimal dry weight is still one of the most difficult and important tasks of a dialysis clinic. The reduction in extracellular volume in haemodialysis implies an improvement in dialysis tolerance. The time factor is one of the principal elements in this control, but it is possible, using other elements, to improve tolerance in 4-5 h sessions and to achieve the proper dry weight associated with normotension in most patients.

reatinine clearance decreases with age by 1 ml/min/year after 40 years of age, although serum creatinine remains constant because of reduction of muscle mass. Reduction of water intake may occur in the elderly because of a reduced sensation of thirst; this is associated with a tendency to lose water with urine. The capacity to respond to sodium load is impaired in aged kidneys, thereby leading to ECV expansion and hypertension. But there is also, in the elderly, a reduced capacity for retaining sodium (FENa is higher than in young subjects), making old subjects sensitive to salt depletion and ECV contraction. Hypernatraemia (Nas > 150 mmol/l) is not infrequent in the elderly (1%) and is usually due to water deficiency (old subjects should be forced to drink), and rarely to iatrogenic excess of sodium. It is the abrupt occurrence of severe hypernatraemia that causes neurological symptoms due to dehydration and brain shrinking, which may lead to cerebral haemorrhage and death. Hyponatraemia (Nas < 130 mmol/l) is frequent among the elderly (7-11%) and is mainly due to water overload, which is usually iatrogenic. Hypovolaemic hyponatraemia occurs when salt depletion causes ECV contraction > 10%, and is due to water retention in an attempt to normalize ECV. Hypervolaemic hyponatraemia is due to ADH hypersecretion because of a decrease in 'effective' circulating blood volume. 'Pseudohyponatraemia' may occur because of hyperlipidaemia or hyperproteinaemia. It is the abrupt occurrence of severe hyponatraemia that causes neurological symptoms (water intoxication), secondary to the oedomatous swelling of the brain within the skull. While rapidly occurring hyponatraemia may be lethal, slowly occurring hyponatraemia is usually asymptomatic. Rapid correction of hyponatraemia may cause cerebral dehydration and 'osmotic demyelination syndrome' ('central pontine myelinosis'). Decrease (e.g. by diuretics) or increase (e.g. by ACE-inhibitors, non-steroidal anti-inflammatory drugs, beta-blockers) or serum potassium may occur in the elderly. Diuretics should be used with caution in elderly subjects to avoid salt depletion, hypotension and renal function impairment.

Five patients on maintenance haemodialysis were exposed to varying degrees of hypernatric dialysate, leading to acute hypernatraemia (plasma sodium concentrations 158 mmol/l to 179 mmol/l). With the exception of one patient, who developed pulmonary oedema, symptoms were minimal and in each case hypernatraemia was corrected without residual complications. The hypernatric dialysate resulted from a granular and less soluble batch of sodium bicarbonate powder. The extra effort required to dissolve the powder caused CO2 to be shaken out of solution, producing sodium carbonate and raising the pH. Mixing calcium from the 'acid' concentrate with excess carbonate in the 'bicarbonate' concentrate led to rapid precipitation of calcium carbonate on the conductivity monitoring cells. Dialysate conductivity was incorrectly sensed as low by the coated conductivity cells, so that an increasing amount of 'acid' concentrate, with its accompanying electrolytes, was delivered to the patient. When the granular powder was ground to a fine powder, passed through a 125 microns sieve and gently dissolved, the machine operated normally. We recommend that sodium bicarbonate powder is supplied with a sieve size no greater than 125 microns, kept dry to prevent the formation of large crystals, and dissolved gently.

Intrarenal dopamine (DA) synthesis, sympathetic activity and sodium homeostasis were studied in eight HLA-identical kidney recipient and donor pairs at 50, 150, and 300 mmol sodium intake. Trimethaphan was given intravenously (i.v.), to mimic acute denervation, tyramine i.v. to induce noradrenaline (NE) release, and the DA precursor DOPA i.v. to study DOPA to DA conversion. Blood pressure was higher in the recipients (P < 0.05) and was not influenced by sodium intake. Cumulative sodium balances were not different between the groups. Sodium intake did not affect DA excretion in either group. The recipients had higher DA (P < 0.05) and DOPA (P < 0.01) excretions and lower urinary DA over DOPA ratio (UDA/DOPA, P < 0.01) and lower NE excretion (P < 0.05) during the whole study. High sodium intake suppressed the UDA/DOPA in both groups (P < 0.05). Trimetaphan decreased renal vascular resistance (RVR) and increased sodium excretion only in the donors (P < 0.05), while GFR increased in both groups. During HiSo tyramine increased RVR in the recipients (P < 0.01) and UDA/DOPA in the donors (P < 0.05). DOPA infusion increased DA excretion four to fivefold but did not change sodium excretion in either group. It is concluded that the recipients maintained sodium homeostasis well but seem to have an impaired functional innervation of the transplanted kidney. NE release seem to stimulate intrarenal DOPA to DA conversion. In both groups a direct relation between DA and sodium excretion was lacking.

Udgivelsesdato: 2008-Oct