αKlotho and vascular calcification: an evolving paradigm.

PURPOSE OF REVIEW: Cardiovascular disease remains the single most serious contributor to mortality in chronic kidney disease (CKD). Although conventional risk factors are prevalent in CKD, both cardiomyopathy and vasculopathy can be caused by pathophysiologic mechanisms specific to the uremic state. CKD is a state of systemic αKlotho deficiency. Although the molecular mechanism of action of αKlotho is not well understood, the downstream targets and biologic functions of αKlotho are astonishingly pleiotropic. An emerging body of literature links αKlotho to uremic vasculopathy. RECENT
FINDINGS: The expression of αKlotho in the vasculature is controversial because of conflicting data. Regardless of whether αKlotho acts as a circulating or resident protein, there are good data associating changes in αKlotho levels with vascular pathology including vascular calcification and in-vitro data of the direct action of αKlotho on both the endothelium and vascular smooth muscle cells in terms of cytoprotection and prevention of mineralization.
SUMMARY: It is critical to understand the pathogenic role of αKlotho on the integral endothelium-vascular smooth muscle network rather than each cell type in isolation in uremic vasculopathy, as αKlotho can serve as a potential prognostic biomarker and a biological therapeutic agent.