We investigate the hypothesis that two DNA elements located upstream of the Klotho gene, displaying a decrease in activity caused by injury accompanied by lower gene expression, are functional enhancers of Klotho. We constructed several lines of mice carrying deletions of different sizes in the two candidate enhancers and investigated the biological consequences of the deletions on gene expression, sexual dimorphism, and the effects of enhancer depletion on acute kidney injury and fibrosis models. The gene discussed is KL; the disease is medical procedure.