Abstract: FR-PO409
Longitudinal Metabolite Associations With Cardiovascular Comorbidity 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
- Mitsnefes, Mark, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 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
- 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
Children with CKD have high prevalence of left ventricular hypertrophy (LVH) and ventricular dysfunction. We evaluated metabolite associations with cardiovascular comorbidities (CV) leveraging baseline and longitudinal follow-up samples from the Chronic Kidney Disease in Children (CKiD) study.
Methods
CKiD is a prospective multicenter cohort of children aged 0.5-16 years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2 at entry. Plasma untargeted metabolomic profiling was available at baseline and years 2 and 4, and echocardiograms at years 2, 4, and 6. LVH and ventricular dysfunction are defined the Figure. Logistic regression identified CV-metabolite associations at baseline. Generalized linear mixed models identified CV-metabolite associations in follow-up. Significance was defined by p<0.05 in both baseline discovery and follow-up replication analyses.
Results
Baseline: n=556, median [IQR] age=11.5 [8.2-15.1] years, eGFR=49.8 [36.6-64.4], LVH 10.9%, and ventricular dysfunction 16.5%. Follow-up: n=328, LVH 9.1%, and ventricular dysfunction 18.4%. Figure shows significant CV-metabolite associations. 4-guanidino-butanoate was the only metabolite that was not associated with eGFR, urine protein:creatinine, FGF23, or dyslipidemia. In a sensitivity analysis with 24-hour ambulatory blood pressure monitoring data: N6-carbamoylthreonyladenosine, 1-methyl-4-imidazoleacetate, and 3-hydroxylaurate remained significantly associated with LVH.
Conclusion
This is one of the first studies to utilize longitudinal metabolomics assessments to replicate cross-sectional CV-metabolite associations in CKD. 4-guanidino-butanoate has been previously associated with the AGMAT gene, reflecting a potential novel genetic-metabolic-CV axis in pediatric CKD. N6-carbamoylthreonyladenosine is interesting in that baseline levels were previously associated with risk of CKD progression.
Funding
- NIDDK Support