title: Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease.
abstract: D-Amino acids, the enantiomers of L-amino acids, are increasingly recognized as novel biomarkers. Although the amounts of D-amino acids are usually very trace in human, some of them have sporadically been detected in blood from patients with kidney diseases. This study examined whether multiple chiral amino acids would be associated with kidney functions, comorbidities, and prognosis of chronic kidney disease (CKD) by enantioselective analyses of all chiral amino acids with a micro-two-dimensional high-performance liquid chromatograph (2D-HPLC)-based analytical platform. 16 out of 21 D-amino acids were detected in plasma from 108 CKD patients in a longitudinal cohort. The levels of D-Ser, D-Pro, and D-Asn were strongly associated with kidney function (estimated glomerular filtration ratio), the levels of D-Ala and D-Pro were associated with age, and the level of D-Asp and D-Pro were associated with the presence of diabetes mellitus. D-Ser and D-Asn were significantly associated with the progression of CKD in mutually-adjusted Cox regression analyses; the risk of composite end point (developing to ESKD or death before ESKD) was elevated from 2.7- to 3.8-fold in those with higher levels of plasma D-Ser and D-Asn. These findings identified chiral amino acids as potential biomarkers in kidney diseases.
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: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamase
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Miyoshi
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: 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: Shiseido Co., Ltd., 1-1-16 Higashi-shimbashi, Minato-ku, Tokyo 105-0021, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mita
authors.affiliation: Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Box B6, 2-2 Yamada-oka, Suita, Osaka, Japan 565-0871.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.|Department of Nephrology, Rinku General Medical Center, 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: D000368:Aged; D000596:Amino Acids / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007536:Isomerism; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000473:pathology*
chemical_list: D000596:Amino Acids; D015415:Biomarkers