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Clin J Am Soc Nephrol. 2018 Apr 6;13(4):560-568. doi: 10.2215/CJN.07650717. Epub 2018 Mar 8.
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 m. 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 m by the end of 6 years of follow-up.
The mean (SD) unadjusted annual change in eGFR was 2.2±2.0 ml/min per 1.73 m 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; <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.
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.
代谢组学有助于确定肾脏功能的新型生物标志物，以辅助慢性肾脏病（CKD）的预防和管理。然而，将代谢组学与估算肾小球滤过率（eGFR）的变化关联的数据尚少，尤其是在遗传背景和环境暴露不同的亚洲人群中。因此，我们旨在调查中国队列中氨基酸和酰基肉碱谱与 eGFR 变化的关联。
设计、地点、参与者和测量：本研究纳入了 1765 名年龄在 50-70 岁之间、基线 eGFR≥60 ml/min per 1.73 m²的社区居住的中国成年人。在基线时，通过气相或液相色谱-质谱联用技术定量检测了血浆中的 22 种氨基酸和 34 种酰基肉碱。计算 eGFR 的年变化率，并将 eGFR 下降定义为在 6 年随访结束时 eGFR<60 ml/min per 1.73 m²。
未经校正的 eGFR 年平均变化为 2.2±2.0 ml/min per 1.73 m²，eGFR 下降的发生率为 16%。经过 Bonferroni 校正，56 种代谢物中有 13 种与 eGFR 年变化显著相关。在对基线协变量（包括基线 eGFR）进行多变量校正后，13 种代谢物中有 7 种，包括半胱氨酸、长链酰基肉碱（C14:1OH、C18、C18:2 和 C20:4）和其他酰基肉碱（C3DC 和 C10），与 eGFR 下降的发生显著相关（代谢物的每标准差增量的相对风险范围为 1.16 至 1.25；在对 13 种代谢物进行多次检测的 Bonferroni 校正后，<3.8E-03）。此外，主成分分析确定了由半胱氨酸和长链酰基肉碱分别组成的两个因子与 eGFR 下降的发生有关。
在中国成年人中，血浆中半胱氨酸和一组酰基肉碱水平升高与 eGFR 下降的发生率增加相关，独立于基线 eGFR 和其他传统危险因素。
