The Protective Function of αKlotho in Chronic Kidney Disease: Evidence and Therapeutic Implications

Chronic kidney disease (CKD) is a prevalent global health problem, resulting in a considerable health burden, with renal fibrosis its principal pathological process. Recent studies have indicated that acute kidney injury (AKI) significantly increases the risk of CKD development. As renal function deteriorates, various complications, including cardiovascular and cerebrovascular diseases and mineral bone disorders, progress rapidly, adversely affecting the long-term survival of CKD patients. αKlotho is an anti-aging protein primarily expressed in renal tubules, exhibiting significant renal protective properties. The reduction of αKlotho expression is common in various kidney diseases, leading to AKI-to-CKD progression, renal fibrosis, and CKD complications through diverse mechanisms. Additionally, αKlotho deficiency may serve as a potential biomarker in the clinical assessment of CKD and its complications, although the research findings in this area are inconclusive. Addressing the reduction of αKlotho levels is crucial for CKD prevention and management. In this paper, we provide an overview of the impact of αKlotho in the progression of AKI to CKD, the upstream and downstream pathways of αKlotho in renal fibrosis, and the role of αKlotho in CKD complications. In addition, potential therapeutic strategies for restoring αKlotho in CKD are explored, including the stimulation of endogenous αKlotho production, αKlotho gene delivery, and the administration of αKlotho protein. Further studies are essential for a better understanding of the role of αKlotho and discovering therapeutic strategies targeted at recovering αKlotho in CKD.