NR1H4 and diabetes mellitus: Several studies have demonstrated that FXR levels are decreased in the kidneys of individuals with diabetes.104 Treatment with FXR agonists improves lipid metabolism, reduces oxidative stress, proteinuria, glomerulosclerosis, and fibrosis in several models of DN.105, –107 These studies suggest a potentially beneficial role for bile acids and the activation of bile acid receptors in preventing kidney injury in response to diabetes and aging.