Metabolomic Signatures of Chronic Kidney Disease of Diverse Etiologies in the Rats and Humans

被引:71
|
作者
Zhang, Zhi-Hao [3 ,4 ]
Chen, Hua [1 ]
Vaziri, Nosratola D. [2 ]
Mao, Jia-Rong [5 ]
Zhang, Li [6 ]
Bai, Xu [7 ]
Zhao, Ying-Yong [1 ,2 ]
机构
[1] Northwest Univ, Coll Life Sci, Key Lab Resource Biol & Biotechnol Western China, Minist Educ, 229 Taibai North Rd, Xian 710069, Shaanxi, Peoples R China
[2] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens, MedSci 1, C352,UCI Campus, Irvine, CA 92897 USA
[3] Oak Ridge Natl Lab, BioEnergy Sci Ctr, Oak Ridge, TN 37831 USA
[4] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA
[5] Shaanxi Inst Tradit Chinese Med, Affiliated Hosp, Dept Nephrol, 2 Xihuamen, Xian 710003, Shaanxi, Peoples R China
[6] Xian 4 Hosp, Dept Nephrol, 21 Jiefang Rd, Xian 710004, Shaanxi, Peoples R China
[7] Waters Technol Shanghai Ltd, Solut Ctr, 1000 Jinhai Rd, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
chronic kidney disease; adenine-induced CKD rats; 5/6 nephrectomized rats; metabolomics; biomarker; irbesartan; enalapril; plasma; CHRONIC-RENAL-FAILURE; SENSITIVITY MASS-SPECTROMETRY; OXIDATIVE STRESS; TUBULOINTERSTITIAL FIBROSIS; LYSOPHOSPHATIDIC ACID; INFLAMMATION; RECEPTOR; MODEL; NRF2; HEMODIALYSIS;
D O I
10.1021/acs.jproteome.6b00583
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Chronic kidney disease (CKD) has emerged as a major public health problem worldwide. It frequently progresses to end-stage renal disease, which is related to very high cost and mortality. Novel biomarkers can provide insight into the novel mechanism, facilitate early detection, and monitor progression of CKD and its response to therapeutic interventions. To identify potential biomarkers, we applied an UPLC-HDMS together with univariate and multivariate statistical analyses using plasma samples from patients with CKD of diverse etiologies (100 sera in discovery set and 120 sera in validation set) and two different rat models of CKD. Using comprehensive screening and validation workflow, we identified a panel of seven metabolites that were shared by all patients and animals regardless of the underlying cause of CKD. These included ricinoleic acid, stearic acid, cytosine, LPA(16:0), LPA(18:2), 3-methylhistidine, and argininic acid. The combination of these seven biomarkers enabled the discrimination of patients with CKD from healthy subjects with a sensitivity of 83.3% and a specificity of 96.7%. In addition, these biomarkers accurately reflected improvements in renal function in response to the therapeutic interventions. Our results indicated that the identified biomarkers may improve the diagnosis of CKD and provide a novel tool for monitoring of the progression of disease and response to treatment in CKD patients.
引用
收藏
页码:3802 / 3812
页数:11
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