Klotho has emerged as an important protein involved in various aspects of chronic kidney disease (CKD) syndrome. It has diagnostic, prognostic and therapeutic potential. Loss of renal klotho is associated with activation of β-catenin in CKD. Klotho levels are reduced in CKD mice and CKD patients, and soft tissue calcification is observed in CKD mice.

A 2013 study suggested that low circulating α-Klotho levels were associated with adverse kidney disease outcome. α-Klotho-deficient mice have been shown to have more rapid progression to CKD after AKI.

A 2017 study suggested that recombinant α-Klotho may be prophylactic and therapeutic for acute to CKD progression and uremic cardiomyopathy.