Neurological disorders are major co-morbidities in patients with kidney disease. While the excess risk of neurological disorders in kidney impairment is known, the etiology and mechanisms behind this link are widely understudied. Decline in kidney function, even in early stages, leads to the build up of uremic toxins in the body. Accumulation of uremic toxins is suggested as a culprit for triggering multiple biologic pathways that can affect brain structural and functional integrity. Metabolic profiling is a high-throughput analysis of metabolites and can be utilized to identify uremic toxins. In this proposal, we aim to identify individual or networks of uremic metabolites and examine their solo or joint associations with impaired brain macro and micro structural integrity and cognitive function. We will then specifically explore the link between these metabolites and incidence of dementia. The aims will be addressed in the framework of the well-characterized multi-ethnic general populations: Rotterdam Study and Multi-Ethnic Study of Atherosclerosis (MESA). Identification of uremic toxins with adverse neurological outcomes is of great importance as it can result in developing strategies to suppress their production and accelerate their removal.
|Effective start/end date||7/1/19 → 6/30/21|
- American Academy of Neurology Institute (AAN 07/15/19)