Loop Diuretics Inhibit Renal Excretion of Trimethylamine N-Oxide

•Uremic retention solutes predominantly eliminate through the kidneys largely via specific efflux channels in the proximal renal tubules.•For the first time, we demonstrated in vivo that renal tubular excretion of TMAO can be inhibited by concomitant loop diuretic administration via competition at the level of renal transporters.•We further observed accumulation of TMAO in the renal parenchyma, which implied differential distributions of TMAO across various tissues and/or systems as a consequence of efflux channel control.•Poorer outcomes in patients who receive long-term loop diuretic agents may therefore be associated with metabolic perturbations, such as retention of metabolites like TMAO, beyond impaired glomerular filtration.