School of Public Health
Patients with kidney impairment exhibit multiple features of accelerated brain aging. It is well established that decline in kidney function, even in early stages, leads to the buildup of circulating uremic toxins. Uremic retention solutes are referred to as uremic toxins when they interact with normal biological functions. Their presence is associated with enhanced oxidative stress, inflammation, and endothelial dysfunction; these elements are specifically linked to impaired brain structure and function. Among the dozens of identified uremic toxins, only a few have been studied for their potential neurotoxic properties. Identification of individual or networks of uremic neurotoxins will significantly advance our knowledge of mechanisms underpinning cognitive aging in kidney impairment and offer novel therapeutic targets. Metabolic profiling is a high-throughput analysis of metabolites and has been utilized previously to characterize novel uremic metabolites associated with cardiovascular risk. This approach will enable us to identify and characterize neurotoxic metabolites affecting the brain structural and functional integrity predisposing individuals to development of dementia. The aim of this project is to identify individual and networks of uremic metabolites that are associated with impaired brain macro and micro structural integrity, cognitive function, and dementia.