Serum metabolomic profiling and incident CKD among African Americans.
Serum metabolomic profiling and incident CKD among African Americans.
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DOI：
10.2215/cjn.11971113
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发表时间：
2014-08
期刊：
影响因子：
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通讯作者：
B. Yu;Yan Zheng;J. Nettleton;Danny C. Alexander;J. Coresh;E. Boerwinkle
中科院分区：
文献类型：
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作者：
B. Yu;Yan Zheng;J. Nettleton;Danny C. Alexander;J. Coresh;E. Boerwinkle
背景和证据需要更准确地反映肾功能和预测未来CKD的新生物标志物。人体代谢组是多种生理或病理生理过程的产物，可以为疾病病因和进展提供新的见解。本研究调查了估计的肾功能是否与多种代谢物相关，以及选定的代谢组学因素是否是CKD事件的独立风险因素。设计、设置、参与者和测量：共有1921名无CKD的非裔美国人纳入动脉粥样硬化风险社区研究，随访时间中位数为19.6年。通过线性回归分析与eGFR（由慢性肾脏病流行病学协作组方程指定）的横截面相关性，并通过考克斯比例风险模型分析与CKD事件的纵向相关性，对通过非靶向气相色谱-质谱法和液相色谱-质谱法定量的共计204种血清代谢物进行了分析。结果发现40种命名代谢物和34种未命名代谢物与慢性肾脏病流行病学协作方程指定的eGFR相关，其中肌酸和3-吲哚硫酸盐显示出最强的阳性（2.8 ml/min/1.73 m（2）/+1 SD; 95%置信区间，2.1 - 3.5）和负相关（-14.2 ml/min/1.73 m（2）/+1 SD; 95%置信区间，-17.0至-11.3）。生存分析中包括204例CKD事件，中位随访时间为19.6年。较高水平的5-氧代脯氨酸（危害比，0.70; 95%置信区间，0.60至0.82）和1，5-脱水葡萄糖醇（危害比，0.68; 95%置信区间，0.58至0.80）与较低的CKD发病风险显著相关，相互调整后，相关性没有明显变化。这些数据确定了大量与肾功能相关的代谢物以及两种作为CKD候选风险因素的代谢物，并可能为CKD生物标志物鉴定提供新的见解。
BACKGROUND AND OBJECTIVES Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD. RESULTS Forty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (-14.2 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, -17.0 to -11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted. CONCLUSIONS These data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification.