KL and Marchiafava-Bignami disease: This study was designed to (a) confirm the potential role of sKlotho as an early biomarker compared with other CKD-MBD biomarkers, (b) to assess whether sKlotho is a reliable indicator of kidney α-Klotho content, (c) to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and (d) to evaluate if autophagy could be involved in the actions of sKlotho.