KL and chronic kidney disease: Recent studies have suggested that excess intake of Pi is a risk factor for the progression of CKD and cardiovascular disease (CVD).(39–41) In addition, intake rates of Pi are increasing worldwide due to an increased consumption of processed foods.(42,43) Notably, our data suggest that the FGF23/Klotho system in 13 month-old mice is malfunction state due to the low level of renal Klotho expression (Fig. 5).