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Klotho deficiency and cognitive impairment in dialysis patients: mechanisms, clinical evidence, and therapeutic
Weiwei Hu1, Yuke Kong1, Jianqin Wang1
1Department of Nephrology, The Second Hospital of Lanzhou University, Lanzhou, China.
Abstract:
Cognitive impairment is highly prevalent among patients with end-stage renal disease (ESRD), particularly those undergoing dialysis, and is associated with poor clinical outcomes and reduced quality of life. Emerging evidence suggests that Klotho, an anti-aging protein predominantly expressed in the kidney, plays a critical role in the pathophysiology of uremia-related cognitive dysfunction. This review summarizes current clinical and experimental evidence regarding Klotho deficiency in dialysis patients and its association with cognitive impairment. We further discuss the underlying mechanisms, including oxidative stress, chronic inflammation, vascular dysfunction, and blood-brain barrier disruption. In addition, the potential role of Klotho as a biomarker and therapeutic target is critically evaluated. Understanding the kidney-brain axis mediated by Klotho may provide novel insights into early identification and targeted intervention for cognitive impairment in dialysis populations.
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