Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction

Cihan Atila; Sara Jessica Camerin; Aleksandra Maleska Maceski; Emanuel J. Miller; Pascal Benkert; Jens Kuhle; Julie Refardt; Mirjam Christ-Crain

doi:10.1093/ejendo/lvag103

Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction

Cihan Atila^*
, Sara Jessica Camerin
, Aleksandra Maleska Maceski
, Emanuel J. Miller
, Pascal Benkert
, Jens Kuhle
, Julie Refardt
, Mirjam Christ-Crain

^*Corresponding author for this work

Internal Medicine

University of Basel
University Hospital Basel

Research output: Contribution to journal › Article › Academic › peer-review

4 Downloads (Pure)

Abstract

Background:

Hyponatremia is the most common electrolyte disorder. While overly rapid correction can cause osmotic demyelination syndrome (ODS), hyponatremia itself is linked to neurocognitive impairment. Despite this, the neurological burden remains underappreciated, and subclinical neuronal and astrocytic injury due to hyponatremia or its correction may be more frequent than recognized. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astrocytic injury.

Objective:

Whether hyponatremia and its treatment are associated with changes in serum NfL and GFAP levels.

Methods:

Two randomized, double-blind, placebo-controlled trials. Study 1: healthy adults underwent experimentally induced hyponatremia within 8 hours. Study 2: hospitalized patients with hyponatremia were treated over 4 days. Biomarkers were measured at baseline and follow-up and analyzed as age- and BMI-adjusted Z-scores (for GFAP, also sex-adjusted).

Results:

In healthy adults, blood sodium decreased by a median of 7 mmol/L [−8(−)–6] within 8 hours, associated with an increase in NfL (+0.48 Z-units [0.09-0.78]) and GFAP (+1.02 Z-units [0.84-1.39]). Patients with hyponatremia showed a baseline sodium of 126 mmol/L [122-127], which increased by 4 mmol/L [2-6] within 24 hours. NfL increased from a Z-score of 1.90 [1.06-2.51] by +0.21 [−0.03-0.66]; GFAP increased from 0.16 [−0.55-0.58] by +0.46 [0.12-0.81]. In multivariable models predicting biomarker Z-scores on day 5, both baseline biomarker levels and the degree of sodium increase within 24 hours were significant predictors.

Conclusion:

Hyponatremia and its correction are associated with measurable neuronal and astrocytic injury. NfL and GFAP may serve as early indicators of osmotic brain stress, suggesting ODS may represent only the visible part of a broader spectrum of cerebral vulnerability.

Original language	English
Pages (from-to)	837-847
Number of pages	11
Journal	European Journal of Endocrinology
Volume	194
Issue number	6
DOIs	https://doi.org/10.1093/ejendo/lvag103
Publication status	Published - Jun 2026

Bibliographical note

Publisher Copyright:
© The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1093/ejendo/lvag103Licence: CC BY

Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correctionFinal published version, 815 KBLicence: CC BY

Cite this

@article{6289553be7c64d11b6fc9e6dc0fcbfaf,

title = "Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction",

abstract = "Background: Hyponatremia is the most common electrolyte disorder. While overly rapid correction can cause osmotic demyelination syndrome (ODS), hyponatremia itself is linked to neurocognitive impairment. Despite this, the neurological burden remains underappreciated, and subclinical neuronal and astrocytic injury due to hyponatremia or its correction may be more frequent than recognized. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astrocytic injury.Objective: Whether hyponatremia and its treatment are associated with changes in serum NfL and GFAP levels. Methods: Two randomized, double-blind, placebo-controlled trials. Study 1: healthy adults underwent experimentally induced hyponatremia within 8 hours. Study 2: hospitalized patients with hyponatremia were treated over 4 days. Biomarkers were measured at baseline and follow-up and analyzed as age- and BMI-adjusted Z-scores (for GFAP, also sex-adjusted). Results: In healthy adults, blood sodium decreased by a median of 7 mmol/L [−8(−){\textendash}6] within 8 hours, associated with an increase in NfL (+0.48 Z-units [0.09-0.78]) and GFAP (+1.02 Z-units [0.84-1.39]). Patients with hyponatremia showed a baseline sodium of 126 mmol/L [122-127], which increased by 4 mmol/L [2-6] within 24 hours. NfL increased from a Z-score of 1.90 [1.06-2.51] by +0.21 [−0.03-0.66]; GFAP increased from 0.16 [−0.55-0.58] by +0.46 [0.12-0.81]. In multivariable models predicting biomarker Z-scores on day 5, both baseline biomarker levels and the degree of sodium increase within 24 hours were significant predictors. Conclusion:Hyponatremia and its correction are associated with measurable neuronal and astrocytic injury. NfL and GFAP may serve as early indicators of osmotic brain stress, suggesting ODS may represent only the visible part of a broader spectrum of cerebral vulnerability.",

author = "Cihan Atila and Camerin, \{Sara Jessica\} and \{Maleska Maceski\}, Aleksandra and Miller, \{Emanuel J.\} and Pascal Benkert and Jens Kuhle and Julie Refardt and Mirjam Christ-Crain",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.",

year = "2026",

month = jun,

doi = "10.1093/ejendo/lvag103",

language = "English",

volume = "194",

pages = "837--847",

number = "6",

}

Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction. / Atila, Cihan; Camerin, Sara Jessica; Maleska Maceski, Aleksandra et al.
In: European Journal of Endocrinology, Vol. 194, No. 6, 06.2026, p. 837-847.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction

AU - Atila, Cihan

AU - Camerin, Sara Jessica

AU - Maleska Maceski, Aleksandra

AU - Miller, Emanuel J.

AU - Benkert, Pascal

AU - Kuhle, Jens

AU - Refardt, Julie

AU - Christ-Crain, Mirjam

N1 - Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

PY - 2026/6

Y1 - 2026/6

N2 - Background: Hyponatremia is the most common electrolyte disorder. While overly rapid correction can cause osmotic demyelination syndrome (ODS), hyponatremia itself is linked to neurocognitive impairment. Despite this, the neurological burden remains underappreciated, and subclinical neuronal and astrocytic injury due to hyponatremia or its correction may be more frequent than recognized. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astrocytic injury.Objective: Whether hyponatremia and its treatment are associated with changes in serum NfL and GFAP levels. Methods: Two randomized, double-blind, placebo-controlled trials. Study 1: healthy adults underwent experimentally induced hyponatremia within 8 hours. Study 2: hospitalized patients with hyponatremia were treated over 4 days. Biomarkers were measured at baseline and follow-up and analyzed as age- and BMI-adjusted Z-scores (for GFAP, also sex-adjusted). Results: In healthy adults, blood sodium decreased by a median of 7 mmol/L [−8(−)–6] within 8 hours, associated with an increase in NfL (+0.48 Z-units [0.09-0.78]) and GFAP (+1.02 Z-units [0.84-1.39]). Patients with hyponatremia showed a baseline sodium of 126 mmol/L [122-127], which increased by 4 mmol/L [2-6] within 24 hours. NfL increased from a Z-score of 1.90 [1.06-2.51] by +0.21 [−0.03-0.66]; GFAP increased from 0.16 [−0.55-0.58] by +0.46 [0.12-0.81]. In multivariable models predicting biomarker Z-scores on day 5, both baseline biomarker levels and the degree of sodium increase within 24 hours were significant predictors. Conclusion:Hyponatremia and its correction are associated with measurable neuronal and astrocytic injury. NfL and GFAP may serve as early indicators of osmotic brain stress, suggesting ODS may represent only the visible part of a broader spectrum of cerebral vulnerability.

AB - Background: Hyponatremia is the most common electrolyte disorder. While overly rapid correction can cause osmotic demyelination syndrome (ODS), hyponatremia itself is linked to neurocognitive impairment. Despite this, the neurological burden remains underappreciated, and subclinical neuronal and astrocytic injury due to hyponatremia or its correction may be more frequent than recognized. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astrocytic injury.Objective: Whether hyponatremia and its treatment are associated with changes in serum NfL and GFAP levels. Methods: Two randomized, double-blind, placebo-controlled trials. Study 1: healthy adults underwent experimentally induced hyponatremia within 8 hours. Study 2: hospitalized patients with hyponatremia were treated over 4 days. Biomarkers were measured at baseline and follow-up and analyzed as age- and BMI-adjusted Z-scores (for GFAP, also sex-adjusted). Results: In healthy adults, blood sodium decreased by a median of 7 mmol/L [−8(−)–6] within 8 hours, associated with an increase in NfL (+0.48 Z-units [0.09-0.78]) and GFAP (+1.02 Z-units [0.84-1.39]). Patients with hyponatremia showed a baseline sodium of 126 mmol/L [122-127], which increased by 4 mmol/L [2-6] within 24 hours. NfL increased from a Z-score of 1.90 [1.06-2.51] by +0.21 [−0.03-0.66]; GFAP increased from 0.16 [−0.55-0.58] by +0.46 [0.12-0.81]. In multivariable models predicting biomarker Z-scores on day 5, both baseline biomarker levels and the degree of sodium increase within 24 hours were significant predictors. Conclusion:Hyponatremia and its correction are associated with measurable neuronal and astrocytic injury. NfL and GFAP may serve as early indicators of osmotic brain stress, suggesting ODS may represent only the visible part of a broader spectrum of cerebral vulnerability.

UR - https://www.scopus.com/pages/publications/105042578141

U2 - 10.1093/ejendo/lvag103

DO - 10.1093/ejendo/lvag103

M3 - Article

C2 - 42299484

AN - SCOPUS:105042578141

SN - 0804-4643

VL - 194

SP - 837

EP - 847

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 6

ER -

Neurofilament light chain and glial fibrillary acidic protein as potential early indicators of osmotic brain stress in hyponatremia and its correction

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this