Kidney Week

Abstract: SA-PO796

Concordance of Metabolite Correlations with Measured GFR in Children and Adults

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - III
  October 27, 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

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

Josef Coresh,

• Abraham, Alison G., Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

Alison G. Abraham,

• Denburg, Michelle, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States

Michelle Denburg,

• Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Susan L. Furth,

• Chen, Jingsha, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

Jingsha Chen,

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

Casey Rebholz,

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

Eugene P. Rhee,

• 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,

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

Vasan S. Ramachandran,

• Warady, Bradley A., Children's Mercy Kansas City , Kansas City, Missouri, United States

Bradley A. Warady,

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

Morgan Grams,

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

Lesley Inker,

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

Andrew S. Levey,

Group or Team Name

• CKD Biomarkers Consortium

Background

Metabolites are strongly influenced by reduced GFR but it is unknown whether the associations are similar in adults and children.

Methods

We evaluated an untargeted GC/MS2 and LC/MS2-based metabolomics quantification (Metabolon) of frozen serum from 962 African-American Study of Kidney Disease and Hypertension (AASK) and frozen plasma in 702 Chronic Kidney Disease in Children (CKiD) participants. Metabolites were standardized, log transformed and then correlated to measured GFR (mGFR). GFR was measured using urinary Iothalamate clearance in AASK and plasma Iohexol clearance in CKiD (median (5^th-95^th %ile) GFR of 48 (24-64) in AASK and 57 (23-114) in CKiD).

Results

There very high agreement between the correlation of the 871 metabolites with mGFR in AASK and the corresponding correlation in CKiD (Figure; correlation of the correlations 0.896). Both studies had an excess of negatively correlated metabolites with mGFR, 311 of them at p<0.001 (denoted with red pluses on the lower left quadrant). Creatinine is shown for reference and pseudouridine for being the most negatively correlated. Among these, the negative correlation with mGFR was stronger in CKiD than AASK (mean difference -0.10, p<0.001), likely due to the wider GFR range in CKiD. The first principal component explained 10% and 13% of the variance and had a correlation with mGFR of -0.71 and -0.86 in AASK and CKiD respectively.

Conclusion

GFR is strongly associated with a large proportion of the metabolome concordantly in children and adults with CKD. These findings hold promise for improvements in adjusting for confounding by GFR and developing equations to better estimate GFR that incorporate metabolite data.

Funding

• NIDDK Support – Metabolon funded assays in AASK as part of a collaboration agreement