BackgroundThe syndrome of inappropriate antidiuresis (SIAD) is characterized by a reduction of free water excretion with consecutive hypotonic hyponatremia and is therefore challenging to treat. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresisviaurinary glucose excretion, likely leading to increased electrolyte free water clearance.MethodsIn this randomized, double-blind, placebo-controlled, crossover trial, we compared 4-week treatment with empagliflozin 25 mg/d to placebo in outpatients with chronic SIAD-induced hyponatremia. At baseline and after both treatment cycles, patients underwent different assessments including neurocognitive testing (Montreal Cognitive Assessment [MoCA]). The primary end point was the difference in serum sodium levels between treatments.ResultsFourteen patients, 50% female, with a median age of 72 years (interquartile range [IQR], 65–77), completed the trial. Median serum sodium level at baseline was 131 mmol/L (IQR, 130–132). After treatment with empagliflozin, median serum sodium level rose to 134 mmol/L (IQR, 132–136), whereas no increase was seen with placebo (130 mmol/L; IQR, 128–132), corresponding to a serum sodium increase of 4.1 mmol/L (95% confidence interval [CI], 1.7 to 6.5;P=0.004). Exploratory analyses showed that treatment with empagliflozin led to improved neurocognitive function with an increase of 1.16 (95% CI, 0.05 to 2.26) in the MoCA score. Treatment was well tolerated; no serious adverse events were reported.ConclusionThe SGLT2 inhibitor empagliflozin is a promising new treatment option for chronic SIAD-induced hyponatremia, possibly improving neurocognitive function. Larger studies are needed to confirm the observed treatment effects.Clinical Trial registration number:ClinicalTrials.govNCT03202667.

OBJECTIVE: Hyponatremia in COVID-19 is often due to the syndrome of inadequate antidiuresis (SIAD), possibly mediated by interleukin-6 (IL-6) induced non-osmotic arginine vasopressin (AVP) secretion. We hypothesized an inverse association between IL-6 and plasma sodium concentration, stronger in COVID-19 compared to other respiratory infections. DESIGN: Secondary analysis of a prospective, cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020. METHODS: We included patients with PCR-confirmed COVID-19 and patients with similar symptoms, further subclassified in bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium levels and IL-6 levels. RESULTS: 500 patients were included, 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, 224 (45%) with other viral respiratory infections. In all groups, median [IQR] IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 [28.4, 59.8] vs 9.2 [2.8, 32.7] pg/ml, p<0.0001; bacterial: 122.1 [63.0, 282.0] vs 67.1 [24.9, 252.0] pg/ml, p<0.05; viral: 14.1 [6.9, 84.7] vs 4.3 [2.1, 14.4] pg/ml, p<0.05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: R= −0.48, p<0.001; bacterial: R= −0.25, p=0.05, viral: R= −0.27, p<0.001). CONCLUSIONS: IL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in COVID-19 compared to bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the SIAD in these patients.

Childhood cancer survivors (CCS) are at risk of poor bone health. The potential benefits of high impact loading physical activity (IL-PA) on bone health in CCS are still poorly understood. We found indication that bone health in young CCS can benefit from higher daily duration and number of IL-PA. Our results are promising since performing just a few minutes of IL-PA daily could be a simple and feasible measure to promote bone health in CCS.