Development and Provisional Validation of a Multiplex LC-MRM-MS Test for Timely Kidney Injury Detection in Urine.

LC-MRM-MS kidney injury low-abundance biomarkers protein markers quantitative bottom-up proteomics urine

Journal

Journal of proteome research
ISSN: 1535-3907
Titre abrégé: J Proteome Res
Pays: United States
ID NLM: 101128775

Informations de publication

Date de publication:
03 12 2021
Historique:
pubmed: 5 11 2021
medline: 26 2 2022
entrez: 4 11 2021
Statut: ppublish

Résumé

Kidney injury is a complication frequently encountered in hospitalized patients. Early detection of kidney injury prior to loss of renal function is an unmet clinical need that should be targeted by a protein-based biomarker panel. In this study, we aim to quantitate urinary kidney injury biomarkers at the picomolar to nanomolar level by liquid chromatography coupled to tandem mass spectrometry in multiple reaction monitoring mode (LC-MRM-MS). Proteins were immunocaptured from urinary samples, denatured, reduced, alkylated, and digested into peptides before LC-MRM-MS analysis. Stable-isotope-labeled peptides functioned as internal standards, and biomarker concentrations were attained by an external calibration strategy. The method was evaluated for selectivity, carryover, matrix effects, linearity, and imprecision. The LC-MRM-MS method enabled the quantitation of KIM-1, NGAL, TIMP2, IGFBP7, CXCL9, nephrin, and SLC22A2 and the detection of TGF-β1, cubilin, and uromodulin. Two to three peptides were included per protein, and three transitions were monitored per peptide for analytical selectivity. The analytical carryover was <1%, and minimal urine matrix effects were observed by combining immunocapture and targeted LC-MRM-MS analysis. The average total CV of all quantifier peptides was 26%. The linear measurement range was determined per measurand and found to be 0.05-30 nmol/L. The targeted MS-based method enables the multiplex quantitation of low-abundance urinary kidney injury biomarkers for future clinical evaluation.

Identifiants

pubmed: 34735145
doi: 10.1021/acs.jproteome.1c00532
pmc: PMC8650098
doi:

Substances chimiques

Isotopes 0
Peptides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5304-5314

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Auteurs

Tirsa T van Duijl (TT)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

L Renee Ruhaak (LR)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Nico P M Smit (NPM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Mervin M Pieterse (MM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Fred P H T M Romijn (FPHTM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Natasja Dolezal (N)

Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Jan Wouter Drijfhout (JW)

Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Johan W de Fijter (JW)

Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

Christa M Cobbaert (CM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

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