Different levels of Klotho and extracellular Pi were achieved through (1) genetic manipulation of the Klotho gene, (2) changes in dietary Pi or (3) induction of CKD by unilateral nephrectomy plus contralateral ischemia-reperfusion injury followed by feeding high dietary Pi, which is a combined model of excess Pi and Klotho deficiency. This evidence concerns the gene KL and chronic kidney disease.