Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease.
Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease.
复制标题
DOI：
10.1038/srep26137
复制
发表时间：
2016-05-18
影响因子：
4.6
通讯作者：
Isaka Y
中科院分区：
文献类型：
--
作者：
Kimura T;Hamase K;Miyoshi Y;Yamamoto R;Yasuda K;Mita M;Rakugi H;Hayashi T;Isaka Y
D-氨基酸是 L-氨基酸的对映体，越来越多地被认为是新型生物标志物。尽管D-氨基酸在人体中的含量通常非常微量，但在肾病患者的血液中偶尔检测到其中一些。本研究通过基于微二维高效液相色谱 (2D-HPLC) 的分析平台对所有手性氨基酸进行对映选择性分析，探讨多种手性氨基酸是否与慢性肾病 (CKD) 的肾功能、合并症和预后相关。在纵向队列中，108 名 CKD 患者的血浆中检测到了 21 种 D-氨基酸中的 16 种。 D-Ser、D-Pro 和 D-Asn 的水平与肾功能（估计肾小球滤过率）密切相关，D-Ala 和 D-Pro 的水平与年龄相关，D-Asp 和 D-Pro 的水平与糖尿病的存在相关。在相互调整的 Cox 回归分析中，D-Ser 和 D-Asn 与 CKD 的进展显着相关；在血浆 D-Ser 和 D-Asn 水平较高的患者中，复合终点（发展为 ESKD 或在 ESKD 之前死亡）的风险从 2.7 倍升高至 3.8 倍。这些发现将手性氨基酸确定为肾脏疾病的潜在生物标志物。
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.