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Background: The 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 diuresis via urinary glucose excretion, likely leading to increased electrolyte free water clearance., Methods: In 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., Results: Fourteen 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., Conclusion: The 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.gov NCT03202667., Podcast: This article contains a podcast at., (Copyright © 2022 by the American Society of Nephrology.)

Purpose: The syndrome of inappropriate antidiuresis (SIAD) is the main cause of hyponatremia and the SGLT2-inhibitor empagliflozin is a promising new treatment option. A biomarker predicting treatment response could optimize treatment success., Materials and Methods: Secondary analysis of a trial including 84 hospitalized patients with SIAD-induced hyponatremia. Patients were randomized to four days of treatment with empagliflozin 25 mg/d ( n  = 43) or placebo ( n  = 41) with both groups receiving fluid restriction <1000 ml/d. Baseline levels of copeptin, the natriuretic peptides MR-proANP and NT-proBNP and C-reactive protein (CRP) were evaluated as predictors for treatment response defined as absolute sodium change, using linear regression models. Additionally, urinary sodium was assessed as predictor for non-response to fluid restriction alone by constructing the receiver-operating characteristic (ROC) curve., Results: No clinically relevant predictive value for treatment response to empagliflozin could be found for copeptin, MR-proANP, NT-proBNP or CRP. A urinary sodium cut-off of >76 mmol/l led to a specificity of 91.7% [95% confidence interval (CI): 75%, 100%] and sensitivity of 51.9% [33.3%, 70.4%] to predict non-response to fluid restriction alone., Conclusions: Based on our data, no biomarker could be identified as predictor for treatment response to empagliflozin. Urinary sodium was confirmed as a good marker for non-response to fluid restriction in SIAD patients. Clinical trial registration : ClinicalTrials.gov (Number: NCT02874807).

Background: Since no treatment exists for children suffering from upper respiratory tract infections (URTIs) without immunological disorders, we searched for a possible tool to improve the health of these children., Aim: We evaluated whether dietary advice (based on food matrix and food synergy), including standard supportive care, can decrease the number and duration of URTIs in children with recurrent URTIs., Design and Setting: This study was a multicenter randomized controlled trial in two pediatric outpatient clinics in the Netherlands, with 118 children aged one to four years with recurrent URTIs. The dietary advice group received dietary advice plus standard supportive care, while the control group received standard supportive care alone for six months. The dietary advice consisted of green vegetables five times per week, beef three times per week, 300 mL whole milk per day, and whole dairy butter on bread every day. Portion sizes were age-appropriate., Results and Conclusion: Children in the dietary advice group had 4.8 (1.6-9.5) days per month with symptoms of an URTI in the last three months of the study, compared to 7.7 (4.0-12.3) in the control group ( p = 0.028). The total number of URTIs during the six-month study period was 5.7 (0.55) versus 6.8 (0.49), respectively ( p = 0.068). The use of antibiotics was significantly reduced in the dietary advice group, as well as visits to a general practitioner, thereby possibly reducing healthcare costs. The results show a reduced number of days with symptoms of a URTI following dietary advice. The number of infections was not significantly reduced., Competing Interests: The authors declare no conflict of interest.