Fei Guo1,2,3,4,5, Qing Dai6, Xiangchang Zeng1,2,3,4,5, Yan Liu6, Zhirong Tan1,2,3,4, Hao Zhang7, Dongsheng Ouyang8,9,10,11,12. 1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People's Republic of China. 2. Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, 410078, People's Republic of China. 3. Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, People's Republic of China. 4. National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China. 5. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, 410000, People's Republic of China. 6. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China. 7. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China. zhanghaoxiangya@163.com. 8. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People's Republic of China. 801940@csu.edu.cn. 9. Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, 410078, People's Republic of China. 801940@csu.edu.cn. 10. Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, People's Republic of China. 801940@csu.edu.cn. 11. National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China. 801940@csu.edu.cn. 12. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, 410000, People's Republic of China. 801940@csu.edu.cn.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: Combinations of TMAO and its precursors were associated with glomerular function and might be utilized in evaluation of CKD.
INTRODUCTION: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 CKDpatients is unknown. Our aim is to investigate the associations of plasma TMAO, choline, L-carnitine and betaine with glomerular filtration in CKDpatients. MATERIALS AND METHODS: A total of 65 CKDpatients and 64 healthy controls were enrolled in this study. Fasting plasma metabolites were detected using liquid chromatography-based method. RESULTS: 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). CONCLUSION: Combinations of TMAO and its precursors were associated with glomerular function and might be utilized in evaluation of CKD.
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