KL and Nephropathy: Using animal model of chronic CNI nephropathy, we firstly reported that CNI treatment decreased Klotho mRNA and protein in the mouse kidney in a dose- and time-dependent manner [43, 47] and Klotho expression was correlated with activity of renin-angiotensin system, tubulointerstitial fibrosis, and marker of oxidative stress (urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion) [48].