Cerebral Neurodegeneration and Cognitive Impairment in Patients on Maintenance Hemodialysis: the Role of Neuroglia and Associated Factors (Review)

Chronic kidney disease (CKD), which often requires maintenance hemodialysis (MHD), represents a model of accelerated aging. Therefore, understanding the mechanisms underlying cerebral neurodegeneration (CND) and cognitive impairment (CI) in patients undergoing MHD is of particular importance. Brain damage in patients with end-stage CKD is considered a multicomponent process associated with the impact of cerebrovascular, neurodegenerative, and numerous dysmetabolic factors. Special attention is given to CND mechanisms mediated by the activation of microglia and astrocytes. The high prevalence of CI in the general population and especially among patients with end-stage CKD undergoing MHD determines the need to clarify CND risk factors and biomarkers. Furthermore, it is essential to explore therapeutic targets, as well as modifiable modern strategies and technologies aimed at slowing the CND progression. This review synthesizes data on the role of neuroglia and associated factors in the development of CND and CI in MHD patients. It presents the mechanisms and factors affecting neuroglia and involved in the pathogenesis of CND and CI. Particular focus is placed on chronic systemic inflammation, the effects of uremic toxins, and the activation of the cerebral renin-angiotensin-aldosterone system. The article studies such chronic systemic inflammatory factors associated with neuroglia as protein S100B, IL-1β, IL-6, TNF-α, and fibrinogen. Experimental and clinical data investigating the impact of uremic toxins (indoxyl sulfate, p-cresol sulfate, and imidazole propionate) on microglia and astrocytes, as well as the activation of the cerebral renin-angiotensin-aldosterone system, are analyzed. Potential further clinical research fields aimed at slowing the CND and CI progression in this patient population are highlighted.