title: Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry.
abstract: The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represented by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous glomerulonephritis (MGN). Since urine metabolites may mirror disease-specific functional perturbations in kidney injury, we examined urine samples for distinctive metabolic changes to identify biomarkers for clinical applications. We developed unbiased multi-component covarianced models from a discovery set with 48 samples (12 healthy controls, 12 MCD, 12 FSGS, and 12 MGN). To extensively validate their diagnostic potential, new batch from 54 patients with primary NS were independently examined a year after. In the independent validation set, the model including citric acid, pyruvic acid, fructose, ethanolamine, and cysteine effectively discriminated each NS using receiver operating characteristic (ROC) analysis except MCD-MGN comparison; nonetheless an additional metabolite multi-composite greatly improved the discrimination power between MCD and MGN. Finally, we proposed the re-constructed metabolic network distinctively dysregulated by the different NSs that may deepen comprehensive understanding of the disease mechanistic, and help the enhanced identification of NS and therapeutic plans for future.
authors.affiliation: The Dept. of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yu Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Se-Yun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yang Gyun
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Chun-Gyoo
authors.initials: CG
authors.lastname: Ihm
authors.affiliation: The Dept. of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Sooah
authors.initials: S
authors.lastname: Kim
authors.affiliation: The Dept. of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Chan-Duck
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The St. Mary's Hospital of Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Cheol Whee
authors.initials: CW
authors.lastname: Park
authors.affiliation: The Dept. of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul, Republic of Korea. Electronic address: rome73@kookmin.ac.kr.
authors.forename: Do Yup
authors.initials: do Y
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address: lshkidney@khu.ac.kr.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D015433:Glomerulonephritis, Membranous / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000652:urine; D009404:Nephrotic Syndrome / Q000652:urine*; D012372:ROC Curve
chemical_list: D015415:Biomarkers
keywords: Bioinformatics; Biomarker panel; Gas-chromatography time-of-flight mass spectrometry; Human urine; Metabolomics; Nephrotic syndrome