NR1H4 and chronic kidney disease: The proximal tubule reabsorbs most filtered bile acids, and enhanced reabsorption of bile acids can promote oxidative damage, inflammation, and the release of vasoactive substances, leading to increased renal vasoconstriction and decreased renal function.110 The FXR can also activate peroxisome proliferator-activated receptor γ, increasing fatty acid oxidation, which may be protective against AKI and CKD (Figure 2).