Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

Abstract

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serumTMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with EGFR (r2=0.31, P,0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM[54.8133.0 μM] for dialysis-dependent patients versus 3.3 μM[3.16.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [minmax] 71.2 μM [29.2189.7 μM] pretransplant versus 11.4 μM [8.920.2 μM] posttransplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-termmortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10mMincrement inTMAOconcentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAOconcentrations correlatewith coronary atherosclerosis burden andmay associate with long-term mortality in patients with CKD undergoing coronary angiography.