title: Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling.
abstract: A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD.
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, 246-2, Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Centre, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.|Department of Nephrology, Rinku General Medical Centre, Izumisano Municipal Hospital, 2-23 Rinku-Orai Kita, Izumisano, Osaka 598-8577, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D000596:Amino Acids / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid; D019075:Electrophoresis, Capillary; D005500:Follow-Up Studies; D006801:Humans; D007536:Isomerism; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000473:pathology*; D013058:Mass Spectrometry; D055432:Metabolomics; D010949:Plasma / Q000737:chemistry*; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000473:pathology*
chemical_list: D000596:Amino Acids; D015415:Biomarkers