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Abstract: SA-PO930

Metabolomics Identifies New Markers of Tubular Secretory Clearance

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Granda, Michael L., University of Washington, Seattle, Washington, United States
  • Prince, David K., University of Washington, Seattle, Washington, United States
  • Fiehn, Oliver, University of California Davis, Davis, California, United States
  • Chen, Yan, Analysis Group Inc, Los Angeles, California, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background

The proximal tubules eliminate protein-bound solutes and drugs via secretion, an energy dependent process that differs from glomerular filtration. Estimation of secretory clearance remains limited to research settings. We used metabolomic profiling to identify potential solutes that could serve as reliable markers of secretory clearance.

Methods

We quantified 528 small molecular solutes in plasma and timed urine from 50 people in a kidney pharmacokinetic study. We compared the kidney clearance of candidate solutes with the clearance of administered IV furosemide, an avidly secreted minimally filtered drug. We identified solutes favoring secretory clearance over GFR based on regressions of -log10(p-values) for joint associations with furosemide and iohexol clearance. We further explored the prediction of secretory clearance by transformed plasma measurements alone.

Results

Mean age was 56 +13 years; 32% were women. A total of 63 solutes met Bonferroni corrected significance for the association with furosemide clearance (Fig.1). Several solutes demonstrated preferential associations (>90th percentile) with furosemide clearance over GFR. Transformed plasma measurements of 4 solutes were also associated with kidney furosemide clearance in the absence of concomitant urine measurements: 2-[(4-aminobenzoyl)amino]acetic acid, 3’-sialyllactose, galactonic acid, 1,4-cyclohexanedicarboxylic acid.

Conclusion

We identified endogenous solutes that demonstrate properties for potential use as markers of tubular secretory clearance.

Funding

  • NIDDK Support