Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins

Sharon Moe, Kalisha D. O'Neill, Danxia Duan, Sadiq Ahmed, Xuening (Neal) Chen, Stephen B. Leapman, Naomi Fineberg, Kenyon Kopecky

Research output: Contribution to journalArticle

359 Citations (Scopus)

Abstract

Background. In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. Methods. To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. Results. The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by Mac-Neal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P = 0.027). Positive immuno-staining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P ≤ 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium × phosphorus product (P = 0.032 and 0.037). The location of immuno-staining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. Conclusions. In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.

Original languageEnglish
Pages (from-to)638-647
Number of pages10
JournalKidney International
Volume61
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Bone Matrix
Spiral Computed Tomography
Chronic Kidney Failure
Epigastric Arteries
Vascular Calcification
Arteries
Osteopontin
Staining and Labeling
Proteins
Kidney Transplantation
Phosphorus
Tunica Intima
Calcium
Collagen Type I
Vascular Smooth Muscle
Osteogenesis
Smooth Muscle Myocytes
Alkaline Phosphatase
Coronary Artery Disease
Immunohistochemistry

Keywords

  • Atherosclerotic disease
  • Calcium, dialysis
  • Extra-skeletal calcification
  • Metastatic calcification
  • Phosphorus
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology

Cite this

Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. / Moe, Sharon; O'Neill, Kalisha D.; Duan, Danxia; Ahmed, Sadiq; Chen, Xuening (Neal); Leapman, Stephen B.; Fineberg, Naomi; Kopecky, Kenyon.

In: Kidney International, Vol. 61, No. 2, 2002, p. 638-647.

Research output: Contribution to journalArticle

Moe, Sharon ; O'Neill, Kalisha D. ; Duan, Danxia ; Ahmed, Sadiq ; Chen, Xuening (Neal) ; Leapman, Stephen B. ; Fineberg, Naomi ; Kopecky, Kenyon. / Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. In: Kidney International. 2002 ; Vol. 61, No. 2. pp. 638-647.
@article{e95c8f03740e4543b91c587a49f377a4,
title = "Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins",
abstract = "Background. In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. Methods. To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. Results. The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by Mac-Neal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P = 0.027). Positive immuno-staining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P ≤ 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium × phosphorus product (P = 0.032 and 0.037). The location of immuno-staining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. Conclusions. In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44{\%}), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.",
keywords = "Atherosclerotic disease, Calcium, dialysis, Extra-skeletal calcification, Metastatic calcification, Phosphorus, Vascular calcification",
author = "Sharon Moe and O'Neill, {Kalisha D.} and Danxia Duan and Sadiq Ahmed and Chen, {Xuening (Neal)} and Leapman, {Stephen B.} and Naomi Fineberg and Kenyon Kopecky",
year = "2002",
doi = "10.1046/j.1523-1755.2002.00170.x",
language = "English",
volume = "61",
pages = "638--647",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins

AU - Moe, Sharon

AU - O'Neill, Kalisha D.

AU - Duan, Danxia

AU - Ahmed, Sadiq

AU - Chen, Xuening (Neal)

AU - Leapman, Stephen B.

AU - Fineberg, Naomi

AU - Kopecky, Kenyon

PY - 2002

Y1 - 2002

N2 - Background. In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. Methods. To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. Results. The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by Mac-Neal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P = 0.027). Positive immuno-staining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P ≤ 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium × phosphorus product (P = 0.032 and 0.037). The location of immuno-staining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. Conclusions. In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.

AB - Background. In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. Methods. To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. Results. The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by Mac-Neal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight (P = 0.027). Positive immuno-staining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P ≤ 0.001), as was a history of coronary artery disease (P < 0.001), and diabetes (P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium × phosphorus product (P = 0.032 and 0.037). The location of immuno-staining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. Conclusions. In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.

KW - Atherosclerotic disease

KW - Calcium, dialysis

KW - Extra-skeletal calcification

KW - Metastatic calcification

KW - Phosphorus

KW - Vascular calcification

UR - http://www.scopus.com/inward/record.url?scp=0036151662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036151662&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2002.00170.x

DO - 10.1046/j.1523-1755.2002.00170.x

M3 - Article

C2 - 11849407

AN - SCOPUS:0036151662

VL - 61

SP - 638

EP - 647

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 2

ER -