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. 2025 May 9;26(1):231.
doi: 10.1186/s12882-025-04130-2.

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

Torunn Axelsson  1 , Henrik Zetterberg  2   3   4   5   6   7 , Kaj Blennow  2   3   8   9 , Burak Arslan  2   3 , Nicholas J Ashton  2 , Markus Axelsson  10 , Maria K Svensson  11   12 , Aso Saeed  13 , Gregor Guron  13
Affiliations

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

Torunn Axelsson et al. BMC Nephrol. .

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.

Keywords: Chronic kidney disease; Glial fibrillary acidic protein; Glomerular filtration rate; Neurofilament light; Tau.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Ethics Committee of the University of Gothenburg approved the study (620-07, 2020-05523), and the research was conducted in accordance with the Helsinki Declaration. All study subjects gave informed written consent to participate. Consent for publication: Not applicable Competing interests: TA, BA and AS declare no conflict of interest. MKS and NJA declare no conflict of interest related to this manuscript. GG has given lectures and/or served at scientific advisory boards for Boehringer Ingelheim, AstraZeneca, Bayer, Novo Nordisk, Vifor Pharma, GSK, Sanofi and Otsuka on topics not related to the content of this manuscript. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, Beckman-Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. MA has received compensation for lectures and/or advisory boards from Biogen, Gazyme and Novartis.

Figures

Fig. 1
Fig. 1
Plasma concentrations of biomarkers of neurological disorders. Box plots with individual data points showing log-transformed plasma concentrations of neurofilament light chain (NfL, A), phosphorylated Tau231 (p-Tau231, B) and glial fibrillary acidic protein (GFAP, C) in patients with chronic kidney disease (CKD, n = 110) and healthy controls (n = 55)
Fig. 2
Fig. 2
Correlations between mGFR and log-transformed plasma concentrations of biomarkers of neurological disorders in patients with CKD. Correlations between measured glomerular filtration rate (mGFR) and log-transformed plasma concentrations of neurofilament light chain (NfL, A), phosphorylated Tau231 (p-Tau231, B) and glial fibrillary acidic protein (GFAP, C) in patients with chronic kidney disease (CKD, n = 110). Linear regression lines are depicted
See this image and copyright information in PMC

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