Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins.
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 MacNeal'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 immunostaining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P < or = 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 x phosphorus product (P=0.032 and 0.037). The location of immunostaining 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.
Moe
Sharon M
SM
Department of Medicine, Indiana University School of Medicine and Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. smoe@iupui.edu
O'Neill
Kalisha D
KD
Duan
Danxia
D
Ahmed
Sadiq
S
Chen
Neal X
NX
Leapman
Stephen B
SB
Fineberg
Naomi
N
Kopecky
Kenyon
K
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D019074:Epigastric Arteries / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin; D010758:Phosphorus / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism*
D024042:Collagen Type I; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D010758:Phosphorus; D000469:Alkaline Phosphatase; D002118:Calcium