ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO785

Metabolomic Profiling for Discovery of Biomarkers of Neurocognitive Impairment in Children with CKD

Session Information

  • Pediatric CKD
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Denburg, Michelle, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Xu, Yunwen, Johns Hopkins School of Public Health, Baltimore, Maryland, United States
  • Abraham, Alison G., Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States
  • Chen, Jingsha, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States
  • Rebholz, Casey, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Rhee, Eugene P., Massachusetts General Hospital, Newton, Massachusetts, United States
  • Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Hooper, Stephen R., University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
  • Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Group or Team Name

  • CKD Biomarkers Consortium
Background

Mechanisms underlying neurocognitive impairment in CKD remain unknown. We sought to perform the first large-scale discovery of novel blood metabolite biomarkers of neurocognitive impairment in children with CKD.

Methods

Untargeted GC/MS2 and LC/MS2-based metabolomics quantification (Metabolon) was performed on baseline plasma samples from 498 Chronic Kidney Disease in Children (CKiD) participants. We applied linear regression models to examine the cross-sectional association between standardized, log transformed metabolites (n=825) and intellectual functioning (IQ score), adjusted for demographics, CKD-related clinical characteristics, and socioeconomic status (SES). Statistical significance was determined using a threshold to keep the false discovery rate (FDR) <0.05.

Results

Cohort characteristics were: 312 (63%) male; median age 12 years (IQR 8,15); median eGFR 52 mL/min/1.73m2 (IQR 38, 64); 377 (76%) non-glomerular diagnosis. Median IQ score was 99 (IQR 87, 108). In unadjusted analyses, 13 metabolites were associated with IQ score. (Figure) Two metabolites, 2-hydroxyarachidate (a fatty acid) and xanthurenate (a product of tryptophan metabolism), were positively associated with IQ independent of age, sex, race, BMI z-score, hypertension, low birthweight/prematurity, glomerular vs. non-glomerular diagnosis, duration of CKD, proteinuria and estimated glomerular filtration rate (eGFR). With additional adjustment for SES, no metabolite associations with IQ were statistically significant.

Conclusion

Untargeted metabolomic profiling identified two metabolites associated with IQ in children with CKD that were independent of most demographic and CKD-related clinical factors, although the inclusion of SES eliminated the statistical significance of these relationships. Further studies are needed to extend these analyses to other neurocognitive domains and delineate mechanisms.

Funding

  • NIDDK Support