Renal Function and Serum Neurofilament Light Chain in Acute Ischemic Stroke: An Observational Cohort Study

Background/Objectives. Neurofilament light chain (NfL) is a biomarker of axonal injury with prognostic value in acute ischemic stroke and a promising surrogate outcome marker. This study evaluated whether serum NfL concentrations in ischemic stroke were modified by varying degrees of renal function. Methods. In this prospective, single-center observational study, patients aged 18-80 y admitted to the IRCCS Mondino Foundation-Stroke Unit between May 2022 and August 2024 were enrolled. Inclusion criteria were: radiologically confirmed ischemic stroke within 24 h of onset, NIHSS ≥ 1 at admission, pre-stroke mRS < 2, no other neurological comorbidities, and eGFR > 30 mL/min/1.73 m². Serum creatinine was measured on admission, and eGFR was calculated using the CKD-EPI equation. Serum NfL was measured by Ella™ immunoassay at T0 (≤24 h), T1 (5 ± 3 d), and T2 (7 ± 3 d). Factors associated with serum NfL concentrations were assessed using linear mixed-effects models, and prognostic associations were evaluated by multivariate logistic regression. Results. Ninety-seven patients were included (median age 68.3 y; 39.2% female). Higher NfL levels were independently associated with lower eGFR (-2.4% per mL/min/1.73 m² increase; 95% CI -3.2% to -1.6%; p < 0.001), and higher NIHSS at admission (+3.5% per point; 95% CI 0.7% to 6.4%; p = 0.014). Time from stroke onset was also associated with NfL (p < 0.001). Among patients with 3-month follow-up and T2 measurement (n = 62), the main effects of log10-transformed NfL at T2 and eGFR were not independently associated with unfavorable outcomes. However, a significant log10 NfL × eGFR interaction was observed (OR 0.22; 95% CI 0.07-0.73; p = 0.014), indicating that the prognostic association of NfL varied according to renal function. Conclusions. Renal function affects serum NfL after ischemic stroke and appears to modify its prognostic association with 3-month outcomes.