Chronic renal failure patients are affected by severe cardiovascular disease secondary to diffuse and progressive vascular calcifications. These calcifications result from the activity of smooth muscle cells which, located in the medium layer of small arteries, transdifferentiate into osteoblast-like cells. Chronic renal failure patients with derangements in mineral metabolism also develop a specific bone disease, known as renal osteodystrophy. Since bone is an endocrine organ capable of synthesizing hormones that regulate bone cells activity, it is possible that the diseased bone of renal patients producing unbalanced amounts of hormones, also affect the pathologic process of vascular calcification. Circulating levels of sclerostin, a bone hormone with powerful activity on bone cells, are increased in renal failure and could potentially inhibit the calcifying osteoblast-like cells in the vessel walls. Aim of our study is to evidence if and to what extent sclerostin is expressed in the small arteries of renal disease patients. We will check, in end stage renal disease patients receiving surgical procedures for arterio-venous fistula creation, sclerostin expression in the vessel walls. Small pieces of arteries (radial arteries) will be obtained to evaluate sclerostin expression and calcium deposition. Further, in these patients, we will assay other local and circulating biomarkers of mineral and bone disorder and of inflammation. Finally, in the same patients will also measure arterial stiffness parameter with ultrasound techniques. We will search for relationships between vascular lesions (histology and instrumental) and biochemical markers. Either negative or positive results will contribute to define the real involvement of sclerostin in the accelerated process of vascular calcifications in renal patients. This information is relevant given the the recent possibility of employing monoclonal anti-sclerostin antibodies to cure metabolic bone diseases.
