The gut-kidney-brain axis in chronic kidney disease: mechanisms and nutritional interventions for cognitive...

Chronic kidney disease (CKD) is increasingly recognised as a systemic disorder extending beyond renal impairment to include cognitive decline. The present review focuses on the mechanisms through which CKD and cognitive impairment are connected in the gut-kidney-brain axis, especially when considering the role played by nutrition as a possible target for interventions. Sources of literature were identified in PubMed, Scopus, Web of Science, and Google Scholar up until 2026 and included in the present analysis clinical trials, systematic reviews and studies in peer-reviewed journals related to nutritional, microbial and cognitive outcomes in CKD. From both interventional and observational data, CKD is characterised by a reduction in short-chain fatty acid (SCFA)-producing bacteria such as Faecalibacterium prausnitzii and Roseburia spp., as well as an increase in proteolytic organisms responsible for uremic toxin production with a consequent elevation in indoxyl sulphate (IS) and p-cresyl sulphate (PCS). Metabolic abnormalities in IS and PCS have been linked to the disruption of blood-brain barrier (BBB), microglial activation, and impaired attention, executive function and memory in human subjects, while animal studies suggest additional impairments including neuronal cell death and learning impairment in hippocampus, although causality cannot be confirmed in humans. Deficiencies of proteins, vitamin B, vitamin D, magnesium, and polyunsaturated fatty acids (PUFAs) are frequently found in CKD and contribute to the above-mentioned problems. Renal-adapted Mediterranean diet, supplementation with micronutrients guided by biomarkers and synbiotics reduce levels of PCS and inflammation, while prebiotics and synbiotics perform better than probiotics, although no cognitive endpoints were defined in most studies.