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Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD
Arthur M Lee1, Yunwen Xu2, Stephen R Hooper3
1Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Clinical Journal of the American Society of Nephrology : CJASN
|October 23, 2023
Summary
Metabolites linked to gut health, energy, and toxins impact children's brain function in chronic kidney disease (CKD). This study identifies key metabolic markers for neurocognitive dysfunction in pediatric CKD patients.
Area of Science:
- Pediatric Nephrology
- Neuroscience
- Metabolomics
Background:
- Children with chronic kidney disease (CKD) face risks of impaired neurocognitive functioning.
- Investigating metabolic profiles can reveal underlying causes of cognitive deficits in pediatric CKD.
Purpose of the Study:
- To identify specific metabolites associated with neurocognitive performance in children with CKD.
- To explore the relationship between metabolic alterations and various domains of neurocognition.
Main Methods:
- Utilized data from the CKiD and NiCK studies, analyzing plasma and serum samples from children with CKD and healthy controls.
- Employed untargeted metabolomic quantification and assessed neurocognitive domains including intelligence, attention, working memory, and executive function.
- Applied linear regression and mixed-effects models, adjusting for relevant clinical factors and eGFR.
Main Results:
- Identified multiple significant associations between specific metabolites and neurocognitive outcomes across analytic samples.
- Observed elevated levels of most associated metabolites in children with CKD compared to controls.
- Highlighted associations with executive function (phenylacetylglutamine, indoleacetylglutamine, trimethylamine N-oxide) and intelligence (γ-glutamyl amino acids, aconitate).
Conclusions:
- Several metabolites are linked to neurocognitive dysfunction in pediatric CKD.
- Findings suggest implications of gut microbiome, mitochondrial dysfunction, altered energy metabolism, and redox homeostasis.
- Metabolomic analysis offers insights into the complex pathophysiology of cognitive impairment in pediatric CKD.
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