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Abstract: FR-PO408

Plasma Metabolome Differences Across Time in Pediatric CKD

Session Information

  • Pediatric Nephrology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Lee, Arthur, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Xu, Yunwen, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Hu, Jian, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Xiao, Rui, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Hooper, Stephen R., University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Hartung, Erum Aftab, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Coresh, Josef, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Ramachandran, Vasan S., Boston University, Boston, Massachusetts, United States
  • Kimmel, Paul L., National Institutes of Health, Bethesda, Maryland, United States
  • Warady, Bradley A., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Denburg, Michelle, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Group or Team Name

  • CKD Biomarkers Consortium
Background

Studies of longitudinal metabolomics in CKD are lacking. Baseline metabolite levels have been associated with risk of future CKD progression (PMC8455058). The relations of change in metabolite levels and eGFR over time are unknown in children with CKD.

Methods

The Chronic Kidney Disease in Children study is a prospective multicenter cohort of children aged 0.5-16 years with eGFR 30-90ml/min/1.73m2 at entry. Untargeted plasma metabolomics profiling was performed on baseline, year 2, and year 4 samples. Linear mixed effects regression (adjusted for sex and baseline age) was used to evaluate eGFR-metabolite associations and metabolite differences over time. Linear regression evaluated association of changes in metabolite level and eGFR. Significance was based on false discovery rate<0.05.

Results

Median (IQR) age=11.6 (8.1-15.1) years and eGFR=49.9 (36.6-64.2). 1156 person-visits (n baseline=626, follow-up=530) were included. Figure shows how metabolites associated with eGFR and time. Changes in 70 metabolite levels associated with change in eGFR. 5 of those increased over time and previously associated with risk of CKD progression: n-acetyl-1methylhistidine, hydroxyasparagine, homocitrulline, N6-carbamoylthreonyladenosine, and 2,3-dihydroxy-5-methylthio-4-pentenoate.

Conclusion

We described plasma metabolomic patterns in relation to eGFR and time in pediatric CKD. There are likely many drivers of metabolite changes over time (eGFR decline, linear growth, pubertal maturation). Longitudinal data corroborated published baseline metabolites associated with future CKD progression. N-acetyl-1-methylhistidine has been associated with risk of kidney failure and NAT8 gene variation in adults. N6-carbamoylthreonyladenosine is a post-transcriptional breakdown product that is gaining interest as a potential uremic toxin.

Funding

  • NIDDK Support