探索慢性肾脏病进展中的肾—脑关系：基于多模态磁共振影像技术的纵向研究

Chronic Kidney Disease (CKD), as its high incidence, can progress to kidney failure and easily be complicated with cognitive impairment, has become a global public health problem.Recent studies suggest that the alteration of brain function in the progress of CKD were closely related to cognitive impairment; however, it is not clear whether the decline of renal function can predict early cognitive impairment. Therefore, exploring the physiological mechanism of renal-brain interaction and search for the early interventional target is the key to prevent CKD cognitive impairment. Currently, the multi-modal magnetic resonance imaging can invasively and comprehensively evaluate renal oxygenation, perfusion, microstructure and fibrosis. This project will conduct a two-year follow-up study of chronic glomerulonephritis induced CKD stage 3 and 4 adopting the latest kidney and brain multi-modal magnetic resonance imaging techniques with multiple imaging data analysis methods, refer to the testing results of neurocognitive scales and clinical biochemical indexes, and dynamically explore and evaluate the relationships among the ‘renal function-brain function-biochemical index-cognitive impairment’.This project is expected to reveal the possible physiological mechanism of kidney-brain interaction in CKD progression in theory and prevent or delay the irreversible brain damage in patients with CKD and reduce the morbidity and mortality of cognitive impairment clinically.

慢性肾脏病（CKD）因其高发病率、可进展至肾衰竭、易并发认知障碍而成为全球性公共健康难题。近年来，研究发现CKD进展过程中脑功能改变与认知障碍密切相关，但肾功能下降能否预测认知障碍并不清楚。为此，积极探索CKD肾脑交互的生理机制和可能的早期干预靶点，是防治CKD认知障碍的关键。目前，多模态肾脏MRI成像技术可以无创、全面的对肾血氧灌注、微观结构及纤维化进行评价。本项目采用最新的多模态肾脏及大脑磁共振技术，使用模式识别及多种影像数据分析技术，结合神经认知量表和临床生化指标的测查，对慢性肾小球肾炎所致CKD3-4阶段的患者进行两年的追踪研究，结合多变量分析方法，动态观察和全面评估CKD各阶段患者肾功能-脑功能-认知障碍-临床生化之间的关系。本研究可望在理论上揭示CKD进展过程中肾脑发生交互作用的生理机制，在临床上可预防或延缓CKD患者大脑不可逆性损伤，对降低CKD认知障碍的发生率具有重要意义。

慢性肾脏病（CKD）因其高发病率、可进展至肾衰竭、易并发认知障碍而成为全球性公共健康难题。近年来，研究发现CKD进展过程中脑功能改变与认知障碍密切相关，但肾功能下降能否预测认知障碍并不清楚。为此，积极探索CKD肾脑交互的生理机制和可能的早期干预靶点，是防治CKD认知障碍的关键。据此，本研究发现（1）与 CKD3 期患者组相比，CKD4 期患者脑白质FA 值减低，MD 值增高，主要位于胼胝体（膝部及体部）、双侧下额枕束、双侧上纵束、双侧下纵束和双侧丘脑前辐射。同时胼胝体膝部 MD值与 DST 评分呈负相关，左侧丘脑前辐射 FA 值与血钙浓度呈正相关。表明 CKD4 期患者存在脑白质微结构的损伤，白质损伤可能与CKD 分期的严重程度有关，并与认知障碍相关。血清钙水平的降低可能是导致CKD 患者脑白质损伤的因素。（2）终末期肾病患者大脑白质FA值普遍降低及MD、AD及RD值普遍升高，主要表现为双侧放射冠、双侧丘脑前辐射、胼胝体体部及膝部、双侧上纵束和右下纵束，提示可能与患者认知损伤有关。（3）终末期肾病患者右侧前额叶皮质（包括 4 个局部峰值顶点，即外侧前额叶皮质、内侧前额叶皮质和腹侧前额叶皮质）厚度减少。 我们研究为终末期肾病患者皮质异常提供了证据。