Metabolomic Analysis of Membranous Glomerulonephritis: Identification of a Diagnostic Panel and Pathogenic Pathways.
Diagnostic model
Membranous glomerulonephritis
Metabolite biomarker
Noninvasive diagnosis
Urinary metabolomics
Journal
Archives of medical research
ISSN: 1873-5487
Titre abrégé: Arch Med Res
Pays: United States
ID NLM: 9312706
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
28
01
2019
revised:
08
07
2019
accepted:
07
08
2019
pubmed:
10
9
2019
medline:
9
4
2020
entrez:
10
9
2019
Statut:
ppublish
Résumé
Primary membranous glomerulonephritis (MGN) is a major cause of nephrotic syndrome in adults. Its diagnosis is based on invasive biopsy, and the current traditional serum or urinary biomarkers, such as the anti-phospholipase A2 receptor, are not adequately sensitive or specific. Our purpose is to identify a sensitive and specific noninvasive panel of biomarkers for the diagnosis of MGN by using metabolomic techniques and to explore the pathogenic pathways that are involved in disease development. The urine metabolome of 66 MGN patients, 31 healthy controls, and 72 disease controls, were analyzed using nuclear magnetic resonance (NMR) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Advanced multivariate statistical analyses were performed for the construction of diagnostic models and biomarker discovery. Receiver operating characteristic (ROC) curve analysis was used to suggest the most sensitive and specific diagnostic panel. The NMR-based diagnostic model showed allantoic acid and deoxyuridine as the most overrepresented and underrepresented biomarkers, respectively differentiating MGN from both control groups. The GC-MS/MS-based diagnostic model showed oxalic acid as the most overrepresented biomarker and 2-hydroxyglutaric acid lactone as the only underrepresented specific biomarker. A panel of a combination of the most accurate predictors of NMR and GC-MS/MS was composed of α-hydroxybutyric acid, 3,4-Dihydroxymandelic acid, 5α-cholestanone, 2-hydroxyglutaric acid lactone, nicotinamide, epicoprostanol, and palmitic acid. Nine impaired pathways were identified in MGN, such as pyrimidine metabolism and NAD salvage. This comprehensive metabolomic study of MGN indicates a panel of promising biomarkers, which is complementary to current traditional biomarkers, and needs to be validated in a larger cohort.
Sections du résumé
BACKGROUND
Primary membranous glomerulonephritis (MGN) is a major cause of nephrotic syndrome in adults. Its diagnosis is based on invasive biopsy, and the current traditional serum or urinary biomarkers, such as the anti-phospholipase A2 receptor, are not adequately sensitive or specific.
AIM OF THE STUDY
Our purpose is to identify a sensitive and specific noninvasive panel of biomarkers for the diagnosis of MGN by using metabolomic techniques and to explore the pathogenic pathways that are involved in disease development.
METHODS
The urine metabolome of 66 MGN patients, 31 healthy controls, and 72 disease controls, were analyzed using nuclear magnetic resonance (NMR) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Advanced multivariate statistical analyses were performed for the construction of diagnostic models and biomarker discovery. Receiver operating characteristic (ROC) curve analysis was used to suggest the most sensitive and specific diagnostic panel.
RESULTS
The NMR-based diagnostic model showed allantoic acid and deoxyuridine as the most overrepresented and underrepresented biomarkers, respectively differentiating MGN from both control groups. The GC-MS/MS-based diagnostic model showed oxalic acid as the most overrepresented biomarker and 2-hydroxyglutaric acid lactone as the only underrepresented specific biomarker. A panel of a combination of the most accurate predictors of NMR and GC-MS/MS was composed of α-hydroxybutyric acid, 3,4-Dihydroxymandelic acid, 5α-cholestanone, 2-hydroxyglutaric acid lactone, nicotinamide, epicoprostanol, and palmitic acid. Nine impaired pathways were identified in MGN, such as pyrimidine metabolism and NAD salvage.
CONCLUSIONS
This comprehensive metabolomic study of MGN indicates a panel of promising biomarkers, which is complementary to current traditional biomarkers, and needs to be validated in a larger cohort.
Identifiants
pubmed: 31499475
pii: S0188-4409(19)30106-7
doi: 10.1016/j.arcmed.2019.08.004
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
159-169Informations de copyright
Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.