Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Quanterix, Billerica, Massachusetts, USA.
Eur J Neurol. 2023 Mar;30(3):729-740. doi: 10.1111/ene.15641. Epub 2022 Dec 9.
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.
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®). Glomerular barrier function was assessed based on albumin-creatinine ratio (ACR); biomarker-creatinine ratios were calculated for correction of urine dilution.
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).
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.
本研究旨在评估急性脑损伤患者尿液中胶质纤维酸性蛋白（GFAP）、神经丝轻链（NfL）、泛素羧基末端水解酶 L1（UCH-L1）和总 tau（t-tau）的定量可测量性。
前瞻性收集急性缺血性脑卒中或脑出血患者（目标组）和健康受试者（对照组）的血清和尿液样本；使用超敏单分子阵列（Simoa®）进行测量。根据白蛋白/肌酐比值（ACR）评估肾小球滤过屏障功能；计算生物标志物/肌酐比值以校正尿液稀释。
在目标组中测量了 93 对尿液-血清样本，在对照组中测量了 10 对尿液-血清样本。目标组和对照组尿液中 GFAP 的平均绝对浓度（±标准偏差）分别为 184.7±362.4 pg/ml 和 27.3±24.1 pg/ml（r=0.3[Wilcoxon 效应量]，p=0.007），NfL 分别为 17.5±38.6 pg/ml 和 0.9±0.3 pg/ml（r=0.4，p<0.005），UCH-L1 分别为 320.2±443.3 pg/ml 和 109.6±116.8 pg/ml（r=0.26，p=0.014），t-tau 分别为 219.5±255.8 pg/ml 和 21.1±27.1 pg/ml（r=0.37，p<0.005），而生物标志物/肌酐比值仅在 NfL（r=0.29，p=0.015）和 t-tau（r=0.32，p<0.01）中存在显著差异。在肾小球滤过屏障完整的患者（ACR<30 mg/g）中，仅在目标组和对照组之间的尿液 NfL 存在显著差异，且与相应的血清浓度呈显著相关性（r=0.58[Pearson 相关系数]，p<0.005）。
四种研究生物标志物均可在尿液中测量，校正尿液稀释后，NfL 和 t-tau 的效应量最大。在肾功能正常的患者中，NfL 显示了血清和尿液浓度之间最准确的关系。
