Kidney Week

Abstract: FR-PO194

Serum Metabolites Associated with Kidney Function Decline

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

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

Authors

• Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States

Morgan Grams,

• Rebholz, Casey, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

Casey Rebholz,

• Tin, Adrienne, Johns Hopkins University, Baltimore, Maryland, United States

Adrienne Tin,

• Chen, Jingsha, Johns Hopkins University, Baltimore, Maryland, United States

Jingsha Chen,

• Ramachandran, Vasan S., Boston University School of Medicine, Framingham, Massachusetts, United States

Vasan S. Ramachandran,

• Anderson, Amanda Hyre, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Amanda Hyre Anderson,

• Levey, Andrew S., Tufts Medical Center, Boston, Massachusetts, United States

Andrew S. Levey,

• Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Inker,

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak,

• Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Harold I. Feldman,

• Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States

Paul L. Kimmel,

• Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States

Sushrut S. Waikar,

• Rhee, Eugene P., Massachusetts General Hospital, Newton, Massachusetts, United States

Eugene P. Rhee,

• Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States

Josef Coresh,

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