TMAO has been reported to promote cardiac remodeling and renal interstitial fibrosis by activating NF-kB and Smad3 (Tang et al., 2015; Yu et al., 2018; Li Z. et al., 2019; Zhang et al., 2021), whereas inhibition of TMAO reduces activation of NF-kB and Smad3, preventing cardiac remodeling and renal interstitial fibrosis in multiple cardiac and renal diseases (Li Z. et al., 2019; Zhang et al., 2021). This evidence concerns the gene SMAD3 and kidney disorder.