Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease.

Tomonori Kimura,Masashi Mita,Kenji Hamase,Keiko Yasuda,Ryohei Yamamoto,Yurika Miyoshi,Terumasa Hayashi,Yoshitaka Isaka,Hiromi Rakugi

doi:10.1038/srep26137

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.

Highlights

D-Amino acids, the enantiomers of L-amino acids, are increasingly recognized as novel biomarkers
We performed a chiral amino acids metabolomic profiling on a longitudinal cohort, which consisted of referred Chronic kidney disease (CKD) patients
We performed a chiral amino acid metabolomic profiling of a cohort consisted of advanced CKD patients, and detected 16 D-amino acids in plasma by utilizing 2D-HPLC system

Summary

Introduction

D-Amino acids, the enantiomers of L-amino acids, are increasingly recognized as novel biomarkers. 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. Several reports suggest the potential relationships between the amounts of D-amino acids and kidney function These lines of reports indicate that the levels of some D-amino acids are correlated with serum creatinine in patients with kidney dysfunction[14,15,16,17,18]. The serum level of D-Ser was shown to increase after ischemia/ reperfusion kidney injury in mice[18] These lines of evidence indicate that D-amino acids are promising candidates as biomarkers for several diseases including kidney diseases, no comprehensive study has been conducted due to the lack of comprehensive analytical platform of D-amino acids. A highly selective two-dimensional high-performance liquid chromatography (2D-HPLC) combined with highly-sensitive fluorescence derivation has shown to be www.nature.com/scientificreports/

Methods

Results

Conclusion