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Abstract: PO2250

Association Between Serum Metabolites and Adverse Renal Outcomes: The Atherosclerosis Risk in Communities (ARIC) Study

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Bernard, Lauren, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Zhou, Linda, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Surapaneni, Aditya L., Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Chen, Jingsha, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Rebholz, Casey, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Yu, Bing, The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Boerwinkle, Eric, The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Coresh, Josef, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Schlosser, Pascal, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Grams, Morgan, Johns Hopkins Medicine, Baltimore, Maryland, United States
Background

Few metabolomic studies have characterized associations between metabolites and end-stage renal disease (ESRD) and kidney failure. Better characterization of the biological underpinnings may help identify at-risk individuals.

Methods

A total of 3,799 participants with serum samples collected at ARIC visit 1 (1987-1989) were included in this analysis. Starting with 318 individual metabolites, we formed clusters of metabolites using Netboost. We then examined longitudinal associations with ESRD and kidney failure using Cox regression. For significant clusters, we also assessed associations of component metabolites with the outcomes. Because the metabolomic profiling was performed in two studies, analyses were performed within each study and then meta-analyzed.

Results

There were 160 ESRD events and 357 kidney failure events during a median follow-up of 23.5 and 23.3 years, respectively. Overall, mean age was 53.5 years, 59.9% were women, and 61.4% were African American. Mean GFR was 107.5 (SD 16.7). We classified metabolites into 43 clusters. Four clusters were significantly associated with ESRD, and all were associated with kidney failure in a directionally consistent manner. Cluster 26 was primarily sugars involved in glycolysis and anaerobic metabolism. Cluster 5 included amino acids involved in liver metabolism using glutathione and gamma glutamyl transferases. Cluster 34 was an assortment of lysolipids involved in creating phospholipid components of cell membranes. Significant component metabolites included: mannose and glucose from cluster 26; gamma-glutamyl tyrosine, gamma-glutamyl threonine, and 5-oxoproline from cluster 5; and 6 lipids in the phosphocholine family from cluster 34. With the exception of mannose and glucose, higher levels of these metabolites were significantly related to lower risk of ESRD and kidney failure.

Conclusion

We identified several related metabolites associated with ESRD and kidney failure. Additional work is needed to determine whether the relationship is causal.

Funding

  • NIDDK Support