Validation of a metabolite panel for a more accurate estimation of glomerular filtration rate using quantitative LC-MS/MS

Tiffany A. Freed, Josef Coresh, Lesley A. Inker, Douglas R. Toal, Regis Perichon, Jingsha Chen, Kelli D. Goodman, Qibo Zhang, Jessie K. Conner, Deirdre M. Hauser, Kate E.T. Vroom, Maria L. Oyaski, Jacob E. Wulff, Gudný Eiríksdóttir, Vilmundur Gudnason, Vicente E. Torres, Lisa A. Ford, Andrew S. Levey

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

BACKGROUND: Clinical practice guidelines recommend estimation of glomerular filtration rate (eGFR) using validated equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). However, when compared with the measured GFR (mGFR), only eGFRcr-cys meets recommended performance standards. Our goal was to develop a more accurate eGFR method using a panel of metabolites without creatinine, cystatin C, or demographic variables. METHODS: An ultra-performance liquid chromatography–tandem mass spectrometry assay for acetylthreonine, phenylacetylglutamine, pseudouridine, and tryptophan was developed, and a 20-day, multiinstrument analytical validation was conducted. The assay was tested in 2424 participants with mGFR data from 4 independent research studies. A new GFR equation (eGFRmet) was developed in a random subset (n 1615) and evaluated in the remaining participants (n 809). Performance was assessed as the frequency of large errors [estimates that differed from mGFR by at least 30% (1 P 30 ); goal 10%]. RESULTS: The assay had a mean imprecision (10% intraassay, 6.9% interassay), linearity over the quantitative range (r 2 0.98), and analyte recovery (98.5%–113%). There was no carryover, no interferences observed, and analyte stability was established. In addition, 1 P 30 in the validation set for eGFRmet (10.0%) was more accurate than eGFRcr (13.1%) and eGFRcys (12.0%) but not eGFRcr-cys (8.7%). Combining metabolites, creatinine, cystatin C, and demographics led to the most accurate equation (7.0%). Neither equation had substantial variation among population subgroups. CONCLUSIONS: The new eGFRmet equation could serve as a confirmatory test for GFR estimation.

Original languageEnglish (US)
Pages (from-to)406-418
Number of pages13
JournalClinical chemistry
Volume65
Issue number3
DOIs
StatePublished - Mar 2019

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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