Chronic Kidney disease and cognitive frailty in aging: molecular crosstalk and clinical implications

Chronic kidney disease (CKD) and cognitive frailty frequently co-occur in older adults, compounding adverse health outcomes and placing substantial strain on healthcare systems.

This review outlines the molecular pathways that link CKD to cognitive decline, including chronic inflammation, oxidative stress, vascular dysfunction, hormonal dysregulation, and interactions along the gut-kidney-brain axis. Recent advances in neuroimaging offer objective biomarkers of brain atrophy, white matter injury, and disrupted functional connectivity.

Multi-omics and single-cell technologies are uncovering cell-type-specific mechanisms and candidate biomarkers, paving the way for precision medicine approaches. Emerging strategies include integrated geriatric-nephrology care models and targeted interventions, such as SGLT2 inhibitors, IL-6 antagonists, microbiome modulation, and structured exercise programs. Bioengineering and artificial intelligence now enable the integration of multimodal data to support risk prediction, disease monitoring, and individualized therapeutic planning. Future priorities should focus on longitudinal cohort studies, interventional trials with cognitive endpoints, and the development of rigorously validated AI-driven predictive models. Effectively addressing CKD-related cognitive frailty will require translating molecular insights into clinical practice to mitigate vulnerability in aging populations.