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

Sadiq Ahmed, Kalisha D. Oneill, Antoinette F. Hood, Andrew P. Evan, Sharon M. Moe

Research output: Contribution to journalArticle

197 Scopus citations

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 α-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.

Original languageEnglish (US)
Pages (from-to)1267-1276
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume37
Issue number6
DOIs
StatePublished - Jan 1 2001

Keywords

  • α-smooth muscle actin
  • Calciphylaxis
  • Matrix vesicles
  • Osteopontin
  • Parathyroid hormone (PTH)
  • Phosphorus
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Nephrology

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