Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells

Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease in dialysis patients due to calcification of cutaneous blood vessels. The pat hogenesis has been attributed to elevated parathyroid hormone (PTH). Howeve r, recent studies evaluating vascular calcification in nondialysis patients have found that the smooth muscle cells play an active role, including pro duction of the bone matrix protein osteopontin, To examine the involvement of various clinical parameters and smooth muscle cells of CUA, we performed a case-control analysis comparing 10 CUA patients with our current dialysi s patients. Available histologic sections were immunostained for osteoponti n, markers of smooth muscle cells, endothelial cells, and macrophages. Comp ared with our current dialysis population, patients with CUA were more like ly to be obese, white, and female (P < 0.02), Comparison of laboratory valu es found CUA patients with lower serum albumin, greater serum phosphorus, a nd greater calcium X phosphorus product (P < 0.01). In contrast, there was no difference in the concentration of PTH or calcium between the 2 groups. Immunostaining of calcified blood vessels showed that all calcified vessels stained positive for osteopontin, whereas all the noncalcifed vessels show ed no osteopontin localization. Staining for smooth muscle alpha -actin dec reased in the medial layer with calcification, with cells appearing to be s loughed off, leading to near occlusion of the vessel lumen. Our case contro l study demonstrates that hyperphosphatemia and an elevated calcium X phosp horus product is associated with CUA. Histologic examination suggests that the calcification is associated with increased expression of osteopontin by smooth muscle cells. (C) 2001 by the National Kidney Foundation, Inc.