Clin J Am Soc Nephrol 2019 01 20;14(1):40-48. Epub 2018 Dec 20.
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland;
Background And Objectives: Nontargeted metabolomics can measure thousands of low-molecular-weight biochemicals, but important gaps limit its utility for biomarker discovery in CKD. These include the need to characterize technical and intraperson analyte variation, to pool data across platforms, and to outline analyte relationships with eGFR.
Design, Setting, Participants, & Measurements: Plasma samples from 49 individuals with CKD (eGFR<60 ml/min per 1.73 m and/or ≥1 g proteinuria) were examined from two study visits; 20 samples were repeated as blind replicates. To enable comparison across two nontargeted platforms, samples were profiled at Metabolon and the Broad Institute.
Results: The Metabolon platform reported 837 known metabolites and 483 unnamed compounds (selected from 44,953 unknown ion features). The Broad Institute platform reported 594 known metabolites and 26,106 unknown ion features. Median coefficients of variation (CVs) across blind replicates were 14.6% (Metabolon) and 6.3% (Broad Institute) for known metabolites, and 18.9% for (Metabolon) unnamed compounds and 24.5% for (Broad Institute) unknown ion features. Median CVs for day-to-day variability were 29.0% (Metabolon) and 24.9% (Broad Institute) for known metabolites, and 41.8% for (Metabolon) unnamed compounds and 40.9% for (Broad Institute) unknown ion features. A total of 381 known metabolites were shared across platforms (median correlation 0.89). Many metabolites were negatively correlated with eGFR at <0.05, including 35.7% (Metabolon) and 18.9% (Broad Institute) of known metabolites.
Conclusions: Nontargeted metabolomics quantifies >1000 analytes with low technical CVs, and agreement for overlapping metabolites across two leading platforms is excellent. Many metabolites demonstrate substantial intraperson variation and correlation with eGFR.