Brain--specific biomarkers in urine as a non--invasive approach to monitor neuronal and glial damage

Background and purpose: This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy--terminal hydrolase L1 (UCH--L1) and total tau (t--tau) in urine of patients with acute cerebral damage. Methods: Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single--molecule arrays (Simoa (R)). Glomerular barrier function was assessed based on albumin--creatinine ratio ( ACR); biomarker--creatinine ratios were calculated for correction of urine dilution. Results: Ninety--three urine--serum pairs in the target group and 10 urine--serum pairs in the control group were measured. The mean absolute concentration +/- standard deviation in urine of the target and control groups were 184.7 +/- 362.4 pg/ml and 27.3 +/- 24.1 pg/ml for GFAP (r = 0.3 [ Wilcoxon effect size], p = 0.007), 17.5 +/- 38.6 pg/ml and 0.9 +/- 0.3 pg/ ml for NfL (r = 0.4, p < 0.005), 320.2 +/- 443.3 pg/ml and 109.6 +/- 116.8 pg/ml for UCH--L1 (r = 0.26, p = 0.014), and 219.5 +/- 255.8 pg/ml and 21.1 +/- 27.1 pg/ml for t--tau (r = 0.37, p < 0.005), respectively, whereas biomarker--creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t--tau (r = 0.32, p < 0.01). In patients with intact glomerular barrier (ACR < 30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation--coefficient], p < 0.005). Conclusion: All four investigated biomarkers could be measured in urine, with NfL and t-tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.