慢性肾病患者血浆中的神经丝轻链、磷酸化tau蛋白231和胶质纤维酸性蛋白浓度升高，且与测得的肾小球滤过率相关。
Plasma concentrations of neurofilament light, p-Tau231 and glial fibrillary acidic protein are elevated in patients with chronic kidney disease and correlate with measured glomerular filtration rate.
作者信息
Axelsson Torunn, Zetterberg Henrik, Blennow Kaj, Arslan Burak, Ashton Nicholas J, Axelsson Markus, Svensson Maria K, Saeed Aso, Guron Gregor
机构信息
Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
出版信息
BMC Nephrol. 2025 May 9;26(1):231. doi: 10.1186/s12882-025-04130-2.
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) 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.
背景
慢性肾脏病（CKD）患者中脑血管疾病和认知障碍的患病率较高。目的是分析CKD患者血浆神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）和磷酸化Tau231（p-Tau231）浓度是否升高，并确定这些生物标志物的独立预测因素，重点关注实测肾小球滤过率（mGFR）的作用。
方法
在这项横断面队列研究中，我们纳入了110例3期和4期CKD患者（估计肾小球滤过率为15 - 59 ml/min/1.73m²），这些患者无明显脑血管疾病或痴呆，以及55名健康对照者。采用超灵敏单分子阵列方法测量神经疾病生物标志物。
结果
与对照组相比，CKD患者血浆NfL浓度（中位数[四分位间距]）为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）和GFAP（190[140 - 281] vs. 153[116 - 211] ng/L，p < 0.001）升高。实测GFR与NfL（r = -0.706，p < 0.001）、p-Tau231（r = -0.561，p < 0.001）和GFAP（r = -0.385，p < 0.001）呈负相关。在多变量线性回归模型中，mGFR是NfL（标准化β系数[β] = -0.439，p < 0.001）和GFAP（β = -0.321，p < 0.001）对数转换后血浆浓度的独立预测因素。
结论
与对照组相比，CKD患者血浆NfL、p-Tau231和GFAP浓度升高，且这些生物标志物与mGFR呈负相关。实测GFR是CKD患者血浆NfL和GFAP浓度的重要独立预测因素。这种关联的潜在机制需要进一步研究。对于GFR显著降低的患者，应谨慎解释NfL和GFAP的血浆水平。
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