Cheng Evelyn, Hung Szu-Chun, Lin Ting-Yun
Department of Medical Education, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Tzu Chi University, Hualien, Taiwan; Bellevue Vision Clinic, Bellevue, WA, USA.
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Tzu Chi University, Hualien, Taiwan.
Clin Nutr. 2025 Jan;44:239-247. doi: 10.1016/j.clnu.2024.12.001. Epub 2024 Dec 4.
Trimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary l-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD).
We prospectively followed 152 nondialysis patients with CKD stages 3-5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing.
The participants had a median age of 66 years, 41.4 % were women, 39.5 % had diabetes, and the median eGFR was 23 mL/min/1.73 m. A rapid decrease in the eGFR occurred in 65 patients (42.8 %) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95 % CI, 1.36-4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC.
Our findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD.
氧化三甲胺（TMAO）是一种由膳食左旋肉碱和胆碱衍生而来的肠道微生物代谢产物。血浆TMAO水平升高与心血管疾病和全因死亡率相关，但关于TMAO及相关代谢产物与慢性肾脏病（CKD）患者肾功能下降风险之间的关联，人们所知甚少。
我们对152例3 - 5期非透析CKD患者进行了前瞻性随访，并通过液相色谱 - 质谱法测量血浆TMAO及相关代谢产物（三甲胺[TMA]、胆碱、肉碱和γ-丁酰甜菜碱）。估计肾小球滤过率（eGFR）斜率>3 ml/min/每1.73 m²/年被定义为快速下降。我们进行逻辑回归以确定eGFR快速或缓慢下降的概率，将每种代谢产物作为主要预测因子。通过全宏基因组测序对肠道微生物群进行分析。
参与者的中位年龄为66岁，41.4%为女性，39.5%患有糖尿病，中位eGFR为23 mL/min/1.73 m²。在中位随访3.3年期间，65例患者（42.8%）的eGFR出现快速下降。在调整基线eGFR、蛋白尿和临床因素后，血浆TMAO水平与eGFR快速下降几率增加独立相关（优势比，2.42；95% CI，1.36 - 4.32），而血浆TMA水平、胆碱、肉碱和γ-丁酰甜菜碱水平则无此关联。eGFR快速下降的患者具有独特的肠道微生物组成，其特征为α多样性增加以及大量产生TMA的细菌，包括脱硫弧菌属和塔纳卡氏柯林斯菌属，以及产生TMA的酶bbuA和cutC的表达增加。
我们的研究结果表明血浆TMAO在CKD患者肾脏疾病进展中具有相关性。
