Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate

Abstract Background Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The objective was to analyse whether plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau231 (...

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Main Authors: Torunn Axelsson, Henrik Zetterberg, Kaj Blennow, Burak Arslan, Nicholas J. Ashton, Markus Axelsson, Maria K. Svensson, Aso Saeed, Gregor Guron
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Nephrology
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Online Access:https://doi.org/10.1186/s12882-025-04130-2
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author Torunn Axelsson
Henrik Zetterberg
Kaj Blennow
Burak Arslan
Nicholas J. Ashton
Markus Axelsson
Maria K. Svensson
Aso Saeed
Gregor Guron
author_facet Torunn Axelsson
Henrik Zetterberg
Kaj Blennow
Burak Arslan
Nicholas J. Ashton
Markus Axelsson
Maria K. Svensson
Aso Saeed
Gregor Guron
author_sort Torunn Axelsson
collection DOAJ
description Abstract Background Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The objective was to analyse whether plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau231 (p-Tau231) are elevated in patients with CKD and to identify independent predictors of these biomarkers, with an emphasis on the role of measured glomerular filtration rate (mGFR). Methods In this cross-sectional cohort study, we included 110 patients with CKD stages 3 and 4 (estimated GFR 15–59 ml/min/1.73 m2) without manifest cerebrovascular disease or dementia, and 55 healthy controls. Biomarkers of neurological disorders were measured with ultrasensitive single molecule array methods. Results Plasma concentrations (median [IQR]) of NfL (37.5 [22.1–47.5] vs. 13.4 [10.5–16.7] ng/L, p < 0.001), p-Tau231 (25.7 [19.1–38.7] vs. 13.9 [10.5–16.3] ng/L, p < 0.001) and GFAP (190 [140–281] vs. 153 [116–211] ng/L, p < 0.001) were elevated in patients with CKD vs. controls. Measured GFR was negatively correlated with NfL (r = − 0.706, p < 0.001), p-Tau231 (r = − 0.561, p < 0.001), and GFAP (r = − 0.385, p < 0.001). In multivariable linear regression models, mGFR was an independent predictor of log-transformed plasma concentrations of NfL (standardized beta coefficient [β] = − 0.439, p < 0.001) and GFAP (β = − 0.321, p < 0.001). Conclusion Patients with CKD had elevated plasma concentrations of NfL, p-Tau231 and GFAP compared with controls, and these biomarkers were inversely correlated with mGFR. Measured GFR was a significant, independent predictor of plasma concentrations of NfL and GFAP in patients with CKD. The mechanisms underlying this association need further investigation. Plasma levels of NfL and GFAP should be interpreted cautiously in patients with marked reductions in GFR.
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spelling doaj-art-7d3581aef2c244ceb94de6afb9b8605f2025-08-20T01:49:44ZengBMCBMC Nephrology1471-23692025-05-0126111010.1186/s12882-025-04130-2Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rateTorunn Axelsson0Henrik Zetterberg1Kaj Blennow2Burak Arslan3Nicholas J. Ashton4Markus Axelsson5Maria K. Svensson6Aso Saeed7Gregor Guron8Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Medical Sciences, Renal Medicine, Uppsala UniversityDepartment of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of GothenburgDepartment of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of GothenburgAbstract Background Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The objective was to analyse whether plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau231 (p-Tau231) are elevated in patients with CKD and to identify independent predictors of these biomarkers, with an emphasis on the role of measured glomerular filtration rate (mGFR). Methods In this cross-sectional cohort study, we included 110 patients with CKD stages 3 and 4 (estimated GFR 15–59 ml/min/1.73 m2) without manifest cerebrovascular disease or dementia, and 55 healthy controls. Biomarkers of neurological disorders were measured with ultrasensitive single molecule array methods. Results Plasma concentrations (median [IQR]) of NfL (37.5 [22.1–47.5] vs. 13.4 [10.5–16.7] ng/L, p < 0.001), p-Tau231 (25.7 [19.1–38.7] vs. 13.9 [10.5–16.3] ng/L, p < 0.001) and GFAP (190 [140–281] vs. 153 [116–211] ng/L, p < 0.001) were elevated in patients with CKD vs. controls. Measured GFR was negatively correlated with NfL (r = − 0.706, p < 0.001), p-Tau231 (r = − 0.561, p < 0.001), and GFAP (r = − 0.385, p < 0.001). In multivariable linear regression models, mGFR was an independent predictor of log-transformed plasma concentrations of NfL (standardized beta coefficient [β] = − 0.439, p < 0.001) and GFAP (β = − 0.321, p < 0.001). Conclusion Patients with CKD had elevated plasma concentrations of NfL, p-Tau231 and GFAP compared with controls, and these biomarkers were inversely correlated with mGFR. Measured GFR was a significant, independent predictor of plasma concentrations of NfL and GFAP in patients with CKD. The mechanisms underlying this association need further investigation. Plasma levels of NfL and GFAP should be interpreted cautiously in patients with marked reductions in GFR.https://doi.org/10.1186/s12882-025-04130-2Chronic kidney diseaseGlial fibrillary acidic proteinGlomerular filtration rateNeurofilament lightTau
spellingShingle Torunn Axelsson
Henrik Zetterberg
Kaj Blennow
Burak Arslan
Nicholas J. Ashton
Markus Axelsson
Maria K. Svensson
Aso Saeed
Gregor Guron
Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
BMC Nephrology
Chronic kidney disease
Glial fibrillary acidic protein
Glomerular filtration rate
Neurofilament light
Tau
title Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
title_full Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
title_fullStr Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
title_full_unstemmed Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
title_short Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
title_sort plasma concentrations of neurofilament light p tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate
topic Chronic kidney disease
Glial fibrillary acidic protein
Glomerular filtration rate
Neurofilament light
Tau
url https://doi.org/10.1186/s12882-025-04130-2
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