Uremic vasculopathy

Recent evidence suggests that uremic vascular calcification is an active cell-mediated process resembling osteogenesis in bone rather than passive precipitation. We have identified increased expression of bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen), and the bone-specific transcription factor core-binding factor alpha-1 (Cbfa1) in histologic sections of inferior epigastric arteries obtained from patients with end-stage renal disease (ESRD) or calcific uremic arteriolopathy. In in vitro experiments, the addition of uremic serum to cultured vascular smooth muscle cells up-regulated osteopontin and Cbfa1 expression and accelerated mineralization. This implies that the uremic milieu may lead to dedifferentiation of vascular smooth muscle cells with subsequent mineralization. Further understanding of the pathophysiology of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in ESRD patients.