Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People's Republic of China.
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, 410078, People's Republic of China.
Int Urol Nephrol. 2021 Mar;53(3):539-551. doi: 10.1007/s11255-020-02632-6. Epub 2020 Sep 18.
Chronic kidney disease (CKD) is characterized by decreased glomerular filtration rate (GFR) due to a variety of causes. Most patients remain undiagnosed at early stage of CKD and proceed to end stage CKD due to unawareness and lacking of efficient biomarkers. Trimethylamine-N-oxide (TMAO) and its predecessor products: choline, L-carnitine and betaine are associated with reduced renal function. However, whether the combined variation of the four metabolites could contribute in prediction and stratification of impaired glomerular function in Chinese CKD patients is unknown. Our aim is to investigate the associations of plasma TMAO, choline, L-carnitine and betaine with glomerular filtration in CKD patients.
A total of 65 CKD patients and 64 healthy controls were enrolled in this study. Fasting plasma metabolites were detected using liquid chromatography-based method.
Plasma TMAO, choline, betaine and L-carnitine levels were differentially correlated with eGFR. The four metabolites were independently associated with CKD after adjustment for multiple traditional risk factors. The combination of the four metabolites had good performance at discriminating CKD from healthy controls (AUC = 0.96) as well as discriminating low eGFR from high eGFR in CKD (AUC = 0.96).
Combinations of TMAO and its precursors were associated with glomerular function and might be utilized in evaluation of CKD.
慢性肾脏病（CKD）的特征是由于各种原因导致肾小球滤过率（GFR）下降。大多数 CKD 患者在早期阶段未被诊断出来，由于缺乏意识和有效的生物标志物，导致疾病进展至终末期 CKD。三甲胺氧化物（TMAO）及其前体产物：胆碱、左旋肉碱和甜菜碱与肾功能下降有关。然而，四种代谢物的联合变化是否有助于预测和分层中国 CKD 患者肾小球功能受损尚不清楚。我们的目的是研究血浆 TMAO、胆碱、左旋肉碱和甜菜碱与 CKD 患者肾小球滤过的关系。
本研究共纳入 65 例 CKD 患者和 64 例健康对照者。采用基于液相色谱的方法检测空腹血浆代谢物。
血浆 TMAO、胆碱、甜菜碱和左旋肉碱水平与 eGFR 呈不同程度的相关性。在调整多种传统危险因素后，这四种代谢物与 CKD 独立相关。四种代谢物的组合在区分 CKD 与健康对照组（AUC=0.96）以及区分 CKD 患者的低 eGFR 和高 eGFR 方面具有良好的性能（AUC=0.96）。
TMAO 及其前体的组合与肾小球功能有关，可能用于 CKD 的评估。
