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

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

Research output: Contribution to journalArticle

195 Citations (Scopus)

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
Pages (from-to)1267-1276
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume37
Issue number6
StatePublished - 2001

Fingerprint

Calciphylaxis
Hyperphosphatemia
Osteopontin
Vascular Smooth Muscle
Smooth Muscle Myocytes
Phosphorus
Dialysis
Calcium
Parathyroid Hormone
Blood Vessels
Vascular Calcification
Bone Matrix
Serum Albumin
Smooth Muscle
Case-Control Studies
Actins
Endothelial Cells
Macrophages
Staining and Labeling
Skin

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. / Ahmed, Sadiq; Oneill, Kalisha D.; Hood, Antoinette F.; Evan, Andrew; Moe, Sharon.

In: American Journal of Kidney Diseases, Vol. 37, No. 6, 2001, p. 1267-1276.

Research output: Contribution to journalArticle

@article{926c0f7249d14815bdd32be07a4307c4,
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 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.",
keywords = "α-smooth muscle actin, Calciphylaxis, Matrix vesicles, Osteopontin, Parathyroid hormone (PTH), Phosphorus, Vascular smooth muscle cells",
author = "Sadiq Ahmed and Oneill, {Kalisha D.} and Hood, {Antoinette F.} and Andrew Evan and Sharon Moe",
year = "2001",
language = "English",
volume = "37",
pages = "1267--1276",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells

AU - Ahmed, Sadiq

AU - Oneill, Kalisha D.

AU - Hood, Antoinette F.

AU - Evan, Andrew

AU - Moe, Sharon

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - α-smooth muscle actin

KW - Calciphylaxis

KW - Matrix vesicles

KW - Osteopontin

KW - Parathyroid hormone (PTH)

KW - Phosphorus

KW - Vascular smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=0034995079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034995079&partnerID=8YFLogxK

M3 - Article

C2 - 11382698

AN - SCOPUS:0034995079

VL - 37

SP - 1267

EP - 1276

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 6

ER -