The impact of kidney dysfunction on blood-brain barrier integrity and neurological conditions

Abstract

Abstract The kidney–brain axis represents a bidirectional pathophysiological link between chronic kidney disease (CKD), acute kidney injury (AKI), and blood–brain barrier (BBB) dysfunction. CKD affects over 800 million individuals globally and is associated with accelerated cognitive decline, stroke, and neurodegenerative disorders. This review synthesizes evidence that uremic toxins, systemic inflammation, oxidative stress, hormonal dysregulation (erythropoietin deficiency, RAAS activation), and gut dysbiosis converge to impair BBB integrity via tight junction degradation, endothelial activation, and pericyte–astrocyte decoupling. These alterations facilitate neuroinflammation, neurotoxicity, and leukocyte infiltration, contributing to the pathogenesis of stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, and CKD-associated leukoencephalopathy. Hemodialysis-induced osmotic shifts and sleep fragmentation further exacerbate BBB and glymphatic dysfunction. Preserving BBB integrity through uremic toxin reduction, anti-inflammatory strategies, RAAS inhibition, and lifestyle interventions (e.g., exercise) emerges as a critical therapeutic goal. Future research must prioritize biomarker validation (claudin-5, S100B), neuroimaging correlations, and targeted BBB-protective therapies to mitigate neurological morbidity in renal disease.