#6067 GUT MICROBE-DERIVED UREMIC TOXIN TRIMETHYLAMINE N-OXIDE CONTRIBUTES TO CARDIAC REMODELING IN PATIENTS ON HEMODIALYSIS
Authors: Pyatchenkov Mikhail , Shсherbakov Evgeniy 
Published: June 2023

Abstract

Background and Aims
It is well established that cardiovascular pathology is the leading cause of increased morbidity and mortality in chronic kidney disease patients, especially in the terminal stage. This is explained by high prevalence of both traditional and non-traditional cardiovascular risk factors, among which inflammation, intestinal dysbiosis and microbe-derived uremic toxins such as indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide (TMAO) are recently considered the most significant. However, the potential underlying mechanisms of these findings have not been fully elucidated. Here we aimed to investigate the association of serum TMAO with echocardiographic parameters of cardiac remodeling in patients receiving hemodialysis treatment.

Method
One hundred and forty (85M, 55F) clinically stable patients on dialysis were studied. The median (interquartile range) age was 56,5 (46,2-60,5) years, median duration of dialysis treatment – 48 (14,5-97) months, 39 (27,9%) were diabetic, 109 (77,9%) had high blood pressure, 39 (27,9%) – previous history of ischemic heart disease, including 8 (5,7%) suffered a myocardial infarction. All patients underwent transthoracic echocardiography (General Electric Vivid E95 device) with the registration of standard parameters. The determination of TMAO in serum was performed by LC/MS using a Shimadzu-8060 system combined with a Shimadzu LC-20AD liquid chromatograph. Statistical analysis was performed with STATISTICA 14.0 program. Non-parametric Spearman's rank correlation method was used to evaluate the associations between serum TMAO level and echocardiographic parameters. Value of p&lt;0.05 was considered statistically significant in all analyses.

Results
Median serum TMAO was 5244 (3588-8701) ng/ml. Echocardiography data: end-systolic left ventricular (LV) size is 38,2±0,6 mm, end-systolic LV volume – 62,0±4,4 ml, end-diastolic LV size – 55,8 ±1,3 mm, end-diastolic LV volume – 111,5±19,7 ml, ejection fraction (according to Simpson method) – 53,2±7,2%, shortening fraction – 28,9±4,4%, inter-ventricular septum thickness – 11,6±0,2 mm, posterior wall thickness – 11,9 ± 0,1 mm, LV mass index – 142,8±4,6 g/m2, LV mass – 298,6±8,8 g, relative wall thickness – 0,43±0,3, number of patients with LV remodeling or hypertrophy – 98 (70%). LV diastolic function parameters (n = 113): E – 0,69±0,2 m/s, A – 0,79±0,2 m/s, E/A (early (E) to late (A) ventricular filling ratio) – 0,89±0,2, deceleration time (DT) – 211±52 ms, number of patients with diastolic disfunction – 104 (74,3%). Statistically significant correlation was fount between TMAO concentration and end-diastolic LV volume (r = 0,315; р = 0,028), LV mass (r = 0,409; р = 0,011) and DT (r = 0,272; р = 0,041). TMAO levels in individuals with LV myocardial hypertrophy and diastolic dysfunction was significantly higher than without these abnormalities (Mann–Whitney U-test р = 0,037 and р = 0,043, correspondingly).

Conclusion
Our results suggest that elevated TMAO may contribute to cardiac remodeling in hemodialysis patients through the myocardial fibrosis and hypertrophy. The pathophysiological mechanisms of TMAO must be investigated further for a better understanding of its role in cardiovascular disease progression and to develop therapeutic interventions against uremic toxicity.