Abstract: TH-PO1111
Serum Metabolomic Biomarkers Associated with Neurocognitive Dysfunction in Youth with CKD
Session Information
- CKD: Clinical, Outcomes, Trials - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Brunson, Celina, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Huang, Lu, Perelman School of Medicine University of Pennsylvania, Philadellphia, Pennsylvania, United States
- Shults, Justine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Furth, Susan L., Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Denburg, Michelle, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Hartung, Erum A., Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Background
CKD is linked to worse neurocognitive (NC) outcomes, possibly related to effects of uremic toxins on the brain. Aims of this study are (1) to compare serum metabolomic profiles of children and young adults with CKD to healthy controls and (2) to evaluate the association between serum metabolite levels and NC outcomes in individuals with CKD.
Methods
Serum untargeted metabolomic profiling (Metabolon, Inc.) was performed in individuals aged 8-25 years with CKD Stage 2-4 (n=65) and matched healthy controls (n=69). Metabolite levels in CKD vs. control groups were compared by multivariable linear regression, with metabolite level as the outcome variable and CKD vs. control as the explanatory variable, adjusted for age, gender, obesity and race. Using the subset of metabolites that differed in CKD vs. controls after Bonferroni correction (threshold p=5.7x10e-7), the relationship of metabolite level and NC outcome within the CKD group was analyzed by multivariable linear regression, with NC composite score as the outcome variable and metabolite level as the explanatory variable, adjusted for estimated glomerular filtration rate (eGFR), glomerular vs. non-glomerular disease, maternal education, income, age, gender, obesity and race. The NC composite score was calculated using the mean of z-scores within 4 domains: intelligence, attention regulation, working memory and executive function.
Results
233 of the 876 metabolites identified differed significantly between CKD and control groups after Bonferroni correction, including metabolites previously found to be associated with CKD and NC dysfunction such as those within the kynurenine/tryptophan and glutamate pathways. Within the CKD group, 6 of the 233 metabolites examined were associated with NC composite score (raw p values <0.05), but the association was not significant after Bonferroni correction.
Conclusion
Youth with CKD have significantly different metabolomic profiles than healthy controls. We did not find an association between metabolite levels and composite NC outcome in the CKD group. However, use of a composite NC score may mask differences in individual NC domains, and adjusting for eGFR may mask associations with renally-cleared metabolites. Future analyses will include examining the relationships of metabolite levels with individual NC domains.
Funding
- NIDDK Support