Work

Usage and limitations of neuroglial biomarkers NfL and GFAP in urine as non-invasive disease markers in multiple sclerosis

Year: 2025

Type: article

Abstract: BACKGROUND: NfL and GFAP in blood are emerging as important biomarkers in MS. A urine-based assay could provide a simpler, non-invasive alternative; however, limited biomarker transfer into urine may pose a major challenge. This study aimed to evaluate the detectability and diagnostic potential of urinary and serum NfL and GFAP for distinguishing MS patients from healthy controls. METHODS: Urine and serum samples from patients with relapsing-remitting MS (RRMS; n = 62) and progressive MS (PMS; n = 17) were analyzed alongside healthy controls (n = 21). NfL and GFAP concentrations were quantified using bead-based immunoassays (Simoa). Pre-analytical validation included inter-/intra-assay precision, reproducibility, and parallelism. Creatinine ratios (CRs) were calculated to adjust for urine dilution. RESULTS: Urinary NfL and GFAP concentrations were detectable but overall low and fell below the assays' validated detection range in most samples. Analyses restricted to valid measurements, as well as sensitivity analyses including all samples, revealed no significant group differences in urinary NfL, GFAP, or their CRs. Subgroup analyses of RRMS patients with or without relapse or MRI contrast enhancement showed similar results. A weak association between serum and urinary NfL was found in univariate regression but not for GFAP. In multivariate models, urinary creatinine concentration, reflecting urine dilution, was the strongest mediator of the measured urinary biomarker levels. CONCLUSION: NfL and GFAP can be detected in urine using ultra-sensitive immunoassays; however, concentrations are very low and strongly influenced by urine dilution. Consequently, urinary NfL and GFAP currently lack reliability for distinguishing MS patients from healthy controls or for monitoring disease activity.

Source: Multiple Sclerosis and Related Disorders

DOI: 10.1016/j.msard.2025.106899