TGR5 regulates appetite, and in the heart, TGR5 signalling helps explain bile-acid cardio-toxicity versus protection: renal FXR lowers TNF-α/NF-κB and fibrosis (limiting AKI-to-CKD), renal TGR5 upregulates aquaporin-2, and FXR contributes to atherogenesis. This evidence concerns the gene AQP2 and chronic kidney disease.