title: Ultrastructural analysis of vascular calcifications in uremia.
abstract: Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2- to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus.
authors.affiliation: Department of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. gschlieper@ukaachen.de
authors.forename: Georg
authors.initials: G
authors.lastname: Schlieper
authors.forename: Anke
authors.initials: A
authors.lastname: Aretz
authors.forename: Steven C
authors.initials: SC
authors.lastname: Verberckmoes
authors.forename: Thilo
authors.initials: T
authors.lastname: Krüger
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Behets
authors.forename: Reza
authors.initials: R
authors.lastname: Ghadimi
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Weirich
authors.forename: Dorothea
authors.initials: D
authors.lastname: Rohrmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Langer
authors.forename: Jan H
authors.initials: JH
authors.lastname: Tordoir
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Ralf
authors.initials: R
authors.lastname: Westenfeld
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
authors.forename: Joachim
authors.initials: J
authors.lastname: Mayer
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.forename: Marc D
authors.initials: MD
authors.lastname: McKee
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D002114:Calcinosis / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D017540:Tunica Media / Q000648:ultrastructure*; D014511:Uremia / Q000150:complications*; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*