title: Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells.
abstract: Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease in dialysis patients due to calcification of cutaneous blood vessels. The pathogenesis has been attributed to elevated parathyroid hormone (PTH). However, recent studies evaluating vascular calcification in nondialysis patients have found that the smooth muscle cells play an active role, including production 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 dialysis patients. Available histologic sections were immunostained for osteopontin, markers of smooth muscle cells, endothelial cells, and macrophages. Compared with our current dialysis population, patients with CUA were more likely to be obese, white, and female (P < 0.02). Comparison of laboratory values found CUA patients with lower serum albumin, greater serum phosphorus, and 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 showed no osteopontin localization. Staining for smooth muscle alpha-actin decreased in the medial layer with calcification, with cells appearing to be sloughed off, leading to near occlusion of the vessel lumen. Our case-control study demonstrates that hyperphosphatemia and an elevated calcium X phosphorus product is associated with CUA. Histologic examination suggests that the calcification is associated with increased expression of osteopontin by smooth muscle cells.
authors.affiliation: Departments of Medicine, Pathology, and Anatomy, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: K D
authors.initials: KD
authors.lastname: O'Neill
authors.forename: A F
authors.initials: AF
authors.lastname: Hood
authors.forename: A P
authors.initials: AP
authors.lastname: Evan
authors.forename: S M
authors.initials: SM
authors.lastname: Moe
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002115:Calciphylaxis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D053495:Osteopontin; D010710:Phosphates / Q000097:blood*; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000473:pathology / Q000628:therapy; D012709:Serum Albumin / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D012867:Skin / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
chemical_list: D010710:Phosphates; C506895:SPP1 protein, human; D012709:Serum Albumin; D012795:Sialoglycoproteins; D053495:Osteopontin; D010758:Phosphorus; D002118:Calcium