Considering the complexity of CKD pathogenesis involving different cell types and changes of multiple signal pathways, multi-target drugs (MTD) emerge as a useful tool; for example, soluble epoxide hydrolase (SHE)-based PTUPB (with cyclo-oxygenase 2 (COX2) inhibitor), PB394 (with PPARγ agonist), and DM509 (with farnesoid X receptor agonist) to alleviate fibrosis, inflammatory response, and oxidative stress from CKD related to DM, hypertension, hyperlipidemia, or other etiologies [166,167,168]. This evidence concerns the gene NR1H4 and chronic kidney disease.