Relationship between Plasma Trimethylamine N-Oxide Levels and Renal Dysfunction in Patients with Hypertension

Abstract

<b><i>Introduction:</i></b> Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients. <b><i>Methods:</i></b> We included healthy controls (<i>n</i> = 50), hypertensive patients (<i>n</i> = 46), and hypertensive patients with renal dysfunction (<i>n</i> = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry. <b><i>Results:</i></b> We found significant differences in plasma TMAO levels among the 3 groups (<i>p</i> < 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with β 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80–0.90). <b><i>Conclusion:</i></b> An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with β 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.

Trimethylamine, a gut bacteria metabolite and air pollutant, increases blood pressure and markers of kidney damage including proteinuria and KIM-1 in rats

“…TMA concentration was higher in the liver (437 nM/g) and kidney in the Da Costa study (531 nM/g) than in our study. TMAO concentration in the liver was over 100-fold higher (633 nM/g) than in our study, while TMAO concentration in the kidneys was not provided by Da Costa et al It needs to be stressed that, in contrast to relatively simple and reproducible measurements of TMAO levels across numerous studies [ 4 , 8 , 10 , 14 , 16 , 18 – 21 , 66 ], the measurements of TMA are much more difficult. There are discrepancies in reported absolute TMA levels across the few available studies [ 11 , 23 , 24 , 33 , 35 , 65 , 67 – 69 ].…”

The potential impact of a probiotic: Akkermansia muciniphila in the regulation of blood pressure—the current facts and evidence

“…Also, recently Zhou et al studied the relationship between circulating plasma TMAO levels and HTN. They found that TMAO levels are higher in patients with HTN than those without HTN [96]. Hsu et al reported that a higher TMA level is associated with high BP load and abnormal 24-h ambulatory BP monitoring profile, along with the reduced abundance of genus Akkermansia [92].…”

“…studied the relationship between circulating plasma TMAO levels and HTN. They found that TMAO levels are higher in patients with HTN than those without HTN [ 96 ]. Hsu et al .…”

Blood–brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins

“…Additionally, our result of increased sCD14 levels correlating with TMAO provides further evidence of gut barrier permeability among KF patients. That progression to KF further disturbs the gut flora and further impairs the intestinal barrier allowing for translocation of uraemic toxins into the systemic circulation thus worsening inflammation leading to negative effects and dysfunction in other organs 69 , 70 . Degradation of occludin in cerebral microvessels in a rat model of ischaemic stroke contributed to BBB disruption and resulted in decreased occludin immunostaining in microvessels, which was reflected by the increased occludin levels in the blood 25 .…”