Klotho and vascular calcification

The link between chronic kidney disease(CKD)and cardiovascular diseases has recently been attracting attention as cardiorenal connection. Vascular calcification due to down-regulation of klotho is partly involved in the pathogenesis of cardiorenal connection. Klotho protein which is mainly expressed in the distal convoluted tubule, is directly correlated with renal function. Of note, its expression has already been decreased in patients with estimated glomerula filtration rate(eGFR)of 60~90 mL/min/1.73 m2 compared with those with eGFR of more than 90 mL/min/1.73 m2. In early CKD, compensatory mechanisms mediated by fibroblast growth factor 23(FGF23)maintain phosphaturia at a sufficient level;however, in end-staging kidney disease, impaired compensatory mechanisms by further down-regulation of klotho promotes osteochondrocytic differentiation of vascular smooth muscle cells(VSMCs)through phosphate hoarding and increased transcription factors. On the other hands, Klotho protein expressed in VSMCs, suppresses osteochondrocytic differentiation with inhibition of phosphate uptake. Both renal and vascular Klotho protect VSMCs against vascular calcification.