Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS/MS

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 standard...

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Bibliographic Details
Published in:Clinical chemistry (Baltimore, Md.) Md.), 2019-03, Vol.65 (3), p.406-418
Main Authors: Freed, Tiffany A, Coresh, Josef, Inker, Lesley A, Toal, Douglas R, Perichon, Regis, Chen, Jingsha, Goodman, Kelli D, Zhang, Qibo, Conner, Jessie K, Hauser, Deirdre M, Vroom, Kate E T, Oyaski, Maria L, Wulff, Jacob E, Eiríksdóttir, Gudný, Gudnason, Vilmundur, Torres, Vicente E, Ford, Lisa A, Levey, Andrew S
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Assaying
Calibration
Chromatography
Chromatography, Liquid - methods
Creatinine
Cystatin C
Demographic variables
Demographics
Demography
Epidermal growth factor receptors
Female
Glomerular Filtration Rate
Glutamine - analogs & derivatives
Glutamine - blood
Humans
Linearity
Liquid chromatography
Male
Mass spectrometry
Mass spectroscopy
Mathematical analysis
Metabolites
Middle Aged
Performance standards
Proteins
Pseudouridine - blood
Reproducibility of Results
Scientific imaging
Stability analysis
Subgroups
Tandem Mass Spectrometry - methods
Threonine - analogs & derivatives
Threonine - blood
Tryptophan
Tryptophan - blood
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Summary: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. 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 ); goal 0.98), and analyte recovery (98.5%-113%). There was no carryover, no interferences observed, and analyte stability was established. In addition, 1 - P 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. The new eGFRmet equation could serve as a confirmatory test for GFR estimation.
ISSN:0009-9147
1530-8561
DOI:10.1373/clinchem.2018.288092