Because renal failure and hyperlipidemia are both associated with accelerated aging features, such as atherosclerosis, oxidative stress and endothelial dysfunction, characteristics also observed in Klotho knockout mice [10]–[12], [25], in this study we investigated the impact of hyperlipidemia-associated renal damage on Klotho expression in kidneys from control and hyperlipidemic Apolipoprotein E (ApoE)-knockout (ApoE KO) mice, a widely used model to study the effect of early onset hyperlipidemia on renal injury [27], [28]. Here, APOE is linked to kidney failure.