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Abstract: FR-PO194

Serum Metabolites Associated with Kidney Function Decline

Session Information

Category: CKD (Non-Dialysis)

  • 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
  • Rebholz, Casey, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Tin, Adrienne, Johns Hopkins University, Baltimore, Maryland, United States
  • Chen, Jingsha, Johns Hopkins University, Baltimore, Maryland, United States
  • Ramachandran, Vasan S., Boston University School of Medicine, Framingham, Massachusetts, United States
  • Anderson, Amanda Hyre, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Levey, Andrew S., Tufts Medical Center, Boston, Massachusetts, United States
  • Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, 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
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Rhee, Eugene P., Massachusetts General Hospital, Newton, Massachusetts, United States
  • Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States

Group or Team Name

  • for the CKD Biomarkers Consortium
Background

Small molecules that associate with subsequent GFR decline in patients with CKD may help uncover novel pathophysiological mechanisms of disease or treatment targets.

Methods

Among 960 participants in the African American Study of Kidney Disease and Hypertension (baseline mGFR 47 +/- 15 ml/min/1.73 m2), we evaluated the associations of 961 named and unnamed serum metabolites identified through untargeted metabolomic profiling with decline in measured GFR over time using linear mixed models and a median of 11 measures of mGFR over 4.1 years. We selected metabolites associated with mGFR decline (p<0.05) and subsequently assessed their associations with ESRD over a median of 8.9 years using Cox models (Bonferroni-corrected p<0.05). Analyses were adjusted for study arm, age, sex, smoking, heart disease, body-mass index, systolic blood pressure, log-transformed proteinuria, and, in the Cox model, baseline measured GFR.

Results

There were 112 metabolites associated with change in mGFR over time in AASK (p<0.05). Fourteen were also associated with ESRD after correcting for multiple comparisons (p<0.0004). All 14 metabolites were negatively associated with baseline mGFR. The top three metabolites associated with ESRD were 1-methylhistidine, erythronate, and O-sulfo-L-tyrosine. Six of the 14 were in the phosphatidylethanolamine pathway.

Conclusion

Several metabolites, including six in the phosphatidylethanolamine pathway, may relate to ESRD risk. Further studies are needed to determine if these associations are causal.

Top Metabolites Associated with mGFR decline and ESRD in AASK

Funding

  • NIDDK Support