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 m(2)) 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.