Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 171 77 Stockholm, Sweden.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 587 58 Linköping, Sweden.
Int J Mol Sci. 2023 Apr 1;24(7):6628. doi: 10.3390/ijms24076628.
Kidney transplantation (KT) may improve the neurological status of chronic kidney disease (CKD) patients, reflected by the altered levels of circulating BBB-specific biomarkers. This study compares the levels of neuron specific enolase (NSE), brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), and circulating plasma extracellular vesicles (EVs) in kidney-failure patients before KT and at a two-year follow up. Using ELISA, NSE, BDNF, and NfL levels were measured in the plasma of 74 living-donor KT patients. Plasma EVs were isolated with ultracentrifugation, and characterized for concentration/size and surface protein expression using flow cytometry from a subset of 25 patients. Lower NSE levels, and higher BDNF and NfL were observed at the two-year follow-up compared to the baseline ( < 0.05). Male patients had significantly higher BDNF levels compared to those of females. BBB biomarkers correlated with the baseline lipid profile and with glucose, vitamin D, and inflammation markers after KT. BBB surrogate marker changes in the microcirculation of early vascular aging phenotype patients with calcification and/or fibrosis were observed only in NSE and BDNF. CD31+ microparticles from endothelial cells expressing inflammatory markers such as CD40 and integrins were significantly reduced after KT. KT may, thus, improve the neurological status of CKD patients, as reflected by changes in BBB-specific biomarkers.
肾移植(KT)可能会改善慢性肾脏病(CKD)患者的神经状态,这反映在循环血脑屏障(BBB)特异性生物标志物水平的改变上。本研究比较了 74 名活体供肾 KT 患者在 KT 前和两年随访时的神经元特异性烯醇化酶(NSE)、脑源性神经营养因子(BDNF)、神经丝轻链(NfL)和循环血浆细胞外囊泡(EVs)的水平。通过 ELISA,测量了 74 名活体供肾 KT 患者血浆中的 NSE、BDNF 和 NfL 水平。使用流式细胞术从 25 名患者的亚组中分离出超离心的血浆 EVs,并对其浓度/大小和表面蛋白表达进行特征分析。与基线相比,两年随访时 NSE 水平降低,BDNF 和 NfL 水平升高(<0.05)。男性患者的 BDNF 水平明显高于女性。BBB 生物标志物与 KT 后的基线脂质谱以及与葡萄糖、维生素 D 和炎症标志物相关。在伴有钙化和/或纤维化的早期血管老化表型患者的微循环中观察到 BBB 替代标志物变化,仅在 NSE 和 BDNF 中观察到。表达炎症标志物如 CD40 和整合素的内皮细胞 CD31+微颗粒在 KT 后显著减少。因此,KT 可能会改善 CKD 患者的神经状态,这反映在 BBB 特异性生物标志物的变化上。