Chronic kidney disease‑associated encephalopathy: Clinical features, pathomechanisms and emerging therapeutic strategies (Review).

Abstract

Chronic kidney disease (CKD) is a progressive disorder whose systemic effects extend to the central nervous system, leading to CKD‑associated encephalopathy. Epidemiological data indicate that the prevalence of cognitive impairment in patients with CKD is as high as 40%, while mood disorders such as depression and anxiety exceed 60% among those receiving hemodialysis, and the risk of cerebrovascular events is also notably increased. These complications substantially impair the quality of life of patients, functional independence and long‑term prognosis, thereby constituting a considerable clinical burden. The key pathological mechanisms involve disruption of the 'gut‑kidney‑brain axis'. Declining renal function leads to the accumulation of gut microbiota‑derived uremic toxins, such as indoxyl sulfate, p‑Cresyl sulfate and trimethylamine N‑oxide. Through multiple pathways, including disruption of blood‑brain barrier integrity, induction of neuroinflammation, promotion of oxidative stress and direct neurotoxicity, these toxins collectively contribute to the injury of the neurovascular unit, neuronal dysfunction and even neurodegeneration. The present review systematically outlines the clinical manifestations, the aforementioned core pathogenic mechanisms and emerging therapeutic strategies for CKD‑associated encephalopathy. Clinically, early identification of neurological complications (such as through neuropsychological assessment, gait analysis and neuroimaging), along with monitoring of specific biomarkers, is crucial for timely intervention and improved prognosis. In terms of treatment, the targeted interventions on the gut‑kidney‑brain axis (such as specific probiotics and intestinal adsorbents), and the advantages and disadvantages of stem cells and gene therapy are summarized in the present review. A deeper understanding of these mechanisms will provide a solid theoretical foundation for the development of innovative treatments and ultimately improve neurological outcomes in patients with CKD.