Altered tryptophan metabolism as a contributor to cognitive impairment in chronic kidney disease: a narrative review
Abstract
Approximately 40% of patients with chronic kidney disease (CKD) experience cognitive impairment (CI), which is strongly associated with increased mortality. CI is driven by multiple factors, including vascular injury, accumulation of uremic toxins, disruption of the blood-brain barrier, and chronic inflammation. Recent evidence suggests that kidney disease and neurocognitive decline are mechanistically linked through dysregulated tryptophan metabolism. Tryptophan is metabolised through three main pathways: the kynurenine, indole, and serotonin pathways, each producing bioactive metabolites with distinct neurophysiological effects. The hallmarks of CKD include chronic inflammation, gut microbial dysbiosis, and impaired renal clearance, all of which alter tryptophan metabolism. Inflammation drives tryptophan metabolism towards the kynurenine pathway, increasing the formation of neurotoxic compounds that promote oxidative stress, excitotoxicity, and neuronal injury. However, reduced availability of tryptophan for serotonin synthesis impairs serotonergic signalling and neurotransmission, as well as melatonin biosynthesis, thereby contributing to circadian rhythm disturbances and impaired glymphatic clearance. Concurrently, gut dysbiosis and reduced renal clearance promote the accumulation of indole-derived uremic toxins, leading to endothelial dysfunction, neuroinflammation, and disruption of the blood-brain barrier. This review highlights the current evidence of dysregulated…
Read the paper
Related studies
- Tryptophan Metabolism and Gut-Brain Homeostasis
- Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review
- Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit
- Relationship between sleep disorders and gut dysbiosis: what affects what?
- The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research
- Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.