Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration Rate
Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration Rate
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血浆氨基酸和酰基肉碱谱与肾小球滤过率降低事件的关联
DOI：
10.2215/cjn.07650717
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Xu Lin
中科院分区：
文献类型：
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作者：
Feijie Wang;Liang Sun;Qi Sun;Liming Liang;Xianfu Gao;Rongxia Li;An Pan;Huaixing Li;Yueyi Deng;Frank B. Hu;Jiarui Wu;Rong Zeng;Xu Lin
背景和目的代谢组学有助于识别新的肾脏功能生物标志物，以帮助预防和管理慢性肾病。然而，将代谢组与eGFR事件联系起来的数据很少，特别是在具有不同遗传背景和环境暴露的亚洲人群中。因此，我们旨在研究中国队列中氨基酸和酰基肉碱谱与eGFR变化的关系....设计、环境、参与者和测量本研究包括1765名年龄在50-70岁、基线eGFR≥60 ml/min / 1.73 m2的社区生活的中国成年人。在基线时，用气相色谱或液相色谱联用质谱法定量血浆中的22种氨基酸和34种酰基肉碱。计算eGFR的年变化率，并将eGFR下降定义为6年随访结束时eGFR<60 ml/min / 1.73 m2 ....结果经校正的eGFR年平均变化（SD）为2.2±2.0 ml/min / 1.73 m2， eGFR降低发生率为16%。经Bonferroni校正后，56种代谢物中有13种与eGFR年变化显著相关。在对基线共变量（包括基线eGFR）进行多变量调整后，13种代谢物中的7种，包括半胱氨酸、长链酰基肉毒碱（C14:1OH、C18、C18:2和C20:4）和其他酰基肉毒碱（C3DC和C10），与eGFR的降低显著相关（相对风险范围为每SD代谢物增加1.16 ~ 1.25；对13种代谢物的多重检测进行Bonferroni校正后P<3.8E-03）。此外，主成分分析确定了两个因素，分别由半胱氨酸和长链酰基肉碱组成，它们与eGFR降低事件相关....结论：血浆半胱氨酸和酰基肉碱水平升高与中国成人eGFR降低发生率升高相关，与基线eGFR和其他传统危险因素无关。
Background and objectives Metabolomics is instrumental in identifying novel biomarkers of kidney function to aid in the prevention and management of CKD. However, data linking the metabolome to incident eGFR are sparse, particularly in Asian populations with different genetic backgrounds and environmental exposures. Therefore, we aimed to investigate the associations of amino acid and acylcarnitine profiles with change in eGFR in a Chinese cohort....Design, setting, participants, & measurements This study included 1765 community-living Chinese adults aged 50–70 years with baseline eGFR≥60 ml/min per 1.73 m2. At baseline, 22 amino acids and 34 acylcarnitines in plasma were quantified by gas or liquid chromatography coupled with mass spectrometry. Annual rate of change in eGFR was calculated, and incident eGFR decline was defined as eGFR<60 ml/min per 1.73 m2 by the end of 6 years of follow-up....Results The mean (SD) unadjusted annual change in eGFR was 2.2±2.0 ml/min per 1.73 m2 and the incidence of reduced eGFR was 16%. After Bonferroni correction, 13 of 56 metabolites were significantly associated with annual eGFR change. After multivariable adjustment of baseline covariates, including baseline eGFR, seven of the 13 metabolites, including cysteine, long-chain acylcarnitines (C14:1OH, C18, C18:2, and C20:4), and other acylcarnitines (C3DC and C10), were significantly associated with incident reduced eGFR (relative risks ranged from 1.16 to 1.25 per SD increment of metabolites; P<3.8E-03 after Bonferroni correction of multiple testing of the 13 metabolites). Moreover, principal component analysis identified two factors, consisting of cysteine and long-chain acylcarnitines, respectively, that were associated with incident reduced eGFR....Conclusions Elevated plasma levels of cysteine and a panel of acylcarnitines were associated with a higher incidence of reduced eGFR in Chinese adults, independent of baseline eGFR and other conventional risk factors.