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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2025-05-01
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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. |
| format | Article |
| id | doaj-art-7d3581aef2c244ceb94de6afb9b8605f |
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| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Nephrology |
| 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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