However, an elevated TMAO level itself leads to an elevated cystatin C level, reduced renal filtration, and ultimately renal dysfunction in mice; conversely, a reduction in TMAO levels attenuates renal functional decline in animal models of chronic kidney disease.39,40 Therefore, heightened TMAO levels may have a direct adverse effect on renal function, and eGFR could also be a mediator of the TMAO-insulin association. This evidence concerns the gene CST3 and chronic kidney disease.