Hyponatremia correction is associated with increased brain-derived neurotrophic factor levels (BDNF) - subanalysis of a randomized, double-blind, placebo-controlled, crossover trial

Eszter Kustos-Toth; Julia Beck; Lucia Seeger; Sophie Monnerat; Cemile Bathelt; Julie Refardt; Mirjam Christ-Crain

doi:10.1530/endoabs.110.P880

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Endocrine Abstracts (2025) 110 P880 | DOI: 10.1530/endoabs.110.P880

ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)

Hyponatremia correction is associated with increased brain-derived neurotrophic factor levels (BDNF) – subanalysis of a randomized, double-blind, placebo-controlled, crossover trial

Eszter Kustos-Toth ^1,2 , Julia Beck ^1,2 , Lucia Seeger ^1,2 , Sophie Monnerat ^1,2 , Cemile Bathelt ^1,2 , Julie Refardt ^1,2 & Mirjam Christ-Crain ^1,2

Author affiliations

¹University Hospital Basel, Endocrinology, diabetes and metabolism, Basel, Switzerland; ²University of Basel, Department of Clinical Research, Basel, Switzerland

JOINT2008

Background: Hyponatremia is the most common electrolyte disorder in clinical practice and is associated with cognitive impairment. We have recently shown that correction of sodium levels can improve cognitive function¹. Growing evidence suggests that serum brain-derived neurotrophic factor (BDNF) correlates with cognitive performance, playing a crucial role in learning, memory, and development of neurocognitive diseases, like dementia and depression. There is currently no data on serum BDNF levels in the context of hyponatremia.

Aim: The primary objective of this study was to investigate the effect of hyponatremia correction on serum BDNF levels.

Design and Methods: Secondary analysis of a prospective randomized, double-blind, crossover, placebo-controlled trial of 4-week empagliflozin 25mg/d vs placebo treatment in patients with syndrome of inappropriate antidiuresis (SIAD), conducted at the University Hospital Basel, Switzerland, from December 2017 to August 2021. Serum BDNF levels were assessed by quantitative enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using R version 4.4.2.

Results: A total of fourteen patients were included in the analysis (50% female, median age 72 years [65–77]. At baseline, the median sodium in the empagliflozin group was 131 mmol/l [128–132], which increased to 134 mmol/l [131–136] after treatment (P = 0,008). In the placebo group, median sodium was 131 mmol/l [130–132] at baseline and remained stable at 131 mmol/l [128–132] after treatment. In the total cohort, an increase in sodium was significantly associated with an increase in BDNF levels (1 mmol/l sodium increase led to a 0.3 ng/ml increase in BDNF levels, P = 0.04), which was more profound after empagliflozin treatment (P = 0.004, compared to placebo P = 0.3). However, in the multivariant model the treatment arm was no independent predictor of BDNF change. In the patients without an increase in sodium, the median BDNF was 11,4ng/ml [10,2–18] at baseline compared to 10,9 ng/ml [8,7–15,7] after treatment. In patients with an increase in sodium, baseline median BDNF was 12,3 ng/ml [9,6–14,7] and increased to 15,2 ng/ml [11,8–19,3] after the treatment period. No association was observed between Montreal Cognitive Assessment (MoCA) scores and BDNF levels, regardless of treatment group.

Conclusion: Our findings indicate that hyponatremia correction increases the serum cognitive marker BDNF, highlighting the importance of hyponatremia correction in cognitive health. Further studies are needed to confirm the role of BDNF upon hyponatremia treatment.

References: 1. Refardt et al, JASN, doi.org/10.1681/ASN.2022050623.