Treatment of cardiovascular calcification in uremia

Uremic subjects, in addition to accelerated atherosclerosis, develop diffuse media vascular calcification (VC) which, in turn, is associated with increased vascular stiffness and mortality risk. Two sets of risk factors for VC can be considered: passive deposition of calcium-phosphate and active transformation of vascular smooth muscle cells into osteoblastic-like cells. The former is linked with the metabolic imbalance in divalent ions that affects renal patients at any stage of the disease; the latter is secondary to a recently discovered mechanism of cellular trans-differentiation caused by deranged local concentration of divalent ions. Also, the role of inhibitors of calcification is under investigation. These include circulating or local, substances like fetuin, matrix GLA protein or osteoprotegerin. Their biologic importance is supported by the occurrence of calcification in transgenic animals lacking these factors. Accordingly, VC is a complex biologic and incompletely understood process that deserves further research, in order to develop specific therapeutic strategies. In general, once established, these calcifications are not considered to be reversible; therefore, prevention is the main treatment option. With this aim, in uremic patients it is now recommended to adopt restricted ranges of serum concentrations for calcium, phosphate and parathyroid hormone which are associated with a lower rate of calcification. To target these recommended ranges, new drugs, like selective vitamin D receptor activators, calcium sensing receptor modulators and calcium free intestinal phosphate binders, have been introduced. Moreover new possible pathogenetic pathways are considered (e.g. vitamin K deficiency). Further, in patients with calciphylaxis, the most severe form of VC, experimental therapies are suggested, with drugs like sodium thiosulphate or bisphosphonates. Drugs capable of reversing the process of trans-differentiation from osteoblast-like to vascular smooth muscle cells could be developed in the future.