慢性肾脏病(chronic kidney disease,CKD)，尤其是终末期肾病(end-stage renal disease,ESRD)患者，普遍存在Klotho-成纤维细胞生长因子23(fibroblast growth factor 23，FGF23)轴功能紊乱。主动脉僵硬是尿毒症透析人群常见且具有重要预后意义的血管功能异常，是心血管事件及死亡风险的独立预测指标。研究表明主动脉僵硬不仅反映心血管损伤，还可通过异常搏动能量向脑微循环过度传递，诱发脑小血管病变及认知功能下降，因此被视为连接“心-肾-脑”损伤的关键血流动力学环节。作为慢性肾脏病矿物质和骨异常(chronic kidney disease-mineral and bone disorder，CKD-MBD)的核心调控系统，Klotho-FGF23轴失衡可通过促进血管钙化、炎症与氧化应激及内皮功能障碍，加速主动脉僵硬进展，并通过脑微循环异常及神经血管单元功能失衡参与认知损伤。本文围绕“Klotho-FGF23轴线紊乱-主动脉僵硬-脑微循环损伤-认知下降”这一通路，综述其机制及临床研究进展，构建透析患者“心-肾-脑”连续损伤模型，为综合管理提供理论依据。

Chronic kidney disease (CKD), particularly the end-stage renal disease (ESRD), is commonly associated with dysfunction of Klotho-FGF23 axis. Aortic stiffness represents one of the most prevalent vascular abnormalities significantly influencing the prognosis of dialysis patients, and is an independent factor for predicting risks of cardiovascular events and mortality. Recent studies have indicated that aortic stiffness indicates the presence of cardiovascular abnormalities, and triggers cerebral microvascular injury and cognitive decline by transmission of the excessive vascular pulse to brain microcirculation. Consequently, aortic stiffness is regarded as a key hemodynamic chain linking ‘cardio-renal-cerebral’ injury. Klotho-FGF23 axis is a core regulatory system relating to CKD-mineral and bone disorder (CKD-MBD). Dysfunction of the axis promotes vascular calcification, inflammation, oxidative stress, and endothelial impairment to accelerate aortic stiffness, which contributes to cerebral microvascular injury and dysfunction of neuro-vascular unit to produce cognitive decline. This paper introduces the ‘Klotho-FGF23 axis dysfunction - aortic stiffness - cerebral microcirculatory impairment - cognitive decline’ pathological pathway to review its mechanism and recent research advances and to construct a ‘heart-kidney-brain’ sequential injury model in dialysis patients, in order to provide theoretical bases for comprehensive management of the injuries.