BMC nephrology · 2025
Utility of trimethylamine N-oxide (TMAO) as a biomarker for risk stratification in chronic kidney disease: a multicenter observational study.
СтатьяНаблюдательное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Lei Yuyan, Jiang Junyi, Chen Lulu, Fang Qing, Li Chaopeng, Fei Yunzhou, Qu Shaonan, Xia Zhiming, Ning Yanhong, He Min, Deng Jin, Zhang Wei, Zhang Hao, Ouyan Dongsheng, Li Xiaohui
Аннотация
BACKGROUND: Chronic kidney disease (CKD) is a significant global health challenge with a multifaceted etiology. Risk stratification and timely intervention are crucial for mitigating CKD progression. Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, has been implicated in CKD pathogenesis. However, the lack of standardized diagnostic assays for TMAO has limited its clinical applicability.
METHODS: We conducted a multicenter observational study in Southern China. Plasma TMAO levels were quantified using a newly developed liquid chromatography-mass spectrometry (LC-MS)-based diagnostic kit in a cohort of 272 participants, including healthy controls and CKD patients. We analyzed the correlation between TMAO levels and renal function indicators, evaluated the utility of TMAO for risk stratification in CKD, and assessed its independent association with reduced eGFR using multivariable logistic regression.
RESULTS: Plasma TMAO levels were significantly elevated in CKD patients compared to healthy controls. TMAO levels increased with CKD severity and exhibited a strong positive correlation with serum creatinine (Scr) and a negative correlation with estimated glomerular filtration rate (eGFR). TMAO levels demonstrated excellent consistency with eGFR in both the full analysis set (FAS) and per protocol set (PPS) populations. Receiver operating characteristic (ROC) curve analysis indicated that TMAO could identify reduced eGFR with high accuracy (AUC: 0.916), which was confirmed by bootstrap validation. After adjusting for age, sex, hypertension, and diabetes, TMAO remained independently associated with reduced eGFR.
CONCLUSIONS: Our findings suggest that TMAO is a promising and independent complementary biomarker for the risk stratification of CKD, though its prognostic value requires validation in longitudinal studies. The developed LC-MS kit enables robust clinical application. Further research is warranted to validate these findings in larger cohorts and explore TMAO's potential as a therapeutic target for CKD management.
TRIAL REGISTRATION: Clinical Trails.gov identifier, ChiCTR2400089774 (retrospectively registered in 14/09/2024).
METHODS: We conducted a multicenter observational study in Southern China. Plasma TMAO levels were quantified using a newly developed liquid chromatography-mass spectrometry (LC-MS)-based diagnostic kit in a cohort of 272 participants, including healthy controls and CKD patients. We analyzed the correlation between TMAO levels and renal function indicators, evaluated the utility of TMAO for risk stratification in CKD, and assessed its independent association with reduced eGFR using multivariable logistic regression.
RESULTS: Plasma TMAO levels were significantly elevated in CKD patients compared to healthy controls. TMAO levels increased with CKD severity and exhibited a strong positive correlation with serum creatinine (Scr) and a negative correlation with estimated glomerular filtration rate (eGFR). TMAO levels demonstrated excellent consistency with eGFR in both the full analysis set (FAS) and per protocol set (PPS) populations. Receiver operating characteristic (ROC) curve analysis indicated that TMAO could identify reduced eGFR with high accuracy (AUC: 0.916), which was confirmed by bootstrap validation. After adjusting for age, sex, hypertension, and diabetes, TMAO remained independently associated with reduced eGFR.
CONCLUSIONS: Our findings suggest that TMAO is a promising and independent complementary biomarker for the risk stratification of CKD, though its prognostic value requires validation in longitudinal studies. The developed LC-MS kit enables robust clinical application. Further research is warranted to validate these findings in larger cohorts and explore TMAO's potential as a therapeutic target for CKD management.
TRIAL REGISTRATION: Clinical Trails.gov identifier, ChiCTR2400089774 (retrospectively registered in 14/09/2024).