Arterial Microcalcification in Atherosclerotic Patients with and Without Chronic Kidney Disease: A Comparative High-Resolution Scanning X-Ray Diffraction Analysis

Abstract

Vascular calcification, albeit heterogeneous in terms of biological and physicochemical properties, has been associated with ageing, lifestyle, diabetes, and chronic kidney disease (CKD). It is unknown whether or not moderately impaired renal function (CKD stages 2-4) affects the physiochemical composition and/or the formation of magnesium-containing tricalcium phosphate ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a high-resolution scanning X-ray diffraction analysis (European Synchrotron Radiation Facility, Grenoble, France) utilizing histological sections of paraffin-embedded arterial specimens derived from atherosclerotic patients with normal renal function (n = 15) and CKD (stages 2-4, n = 13) was performed. This approach allowed us to spatially assess the contribution of calcium phosphate (apatite) and whitlockite to arterial microcalcification. Per group, the number of samples (13 vs. 12) with sufficient signal intensity and total lengths of regions (201 vs. 232 μm) giving rise to diffractograms ("informative regions") were comparable. Summarizing all informative regions per group into one composite sample revealed calcium phosphate/apatite as the leading mineral phase in CKD patients, whereas in patients with normal renal function the relative contribution of whitlockite and calcium phosphate/apatite was on the same order of magnitude (CKD, calcium phosphate/apatite 157 μm, whitlockite 38.7 μm; non-CKD, calcium phosphate/apatite 79.0 μm, whitlockite 94.1 μm; each p < 0.05). Our results, although based on a limited number of samples, indicate that chronic impairment of renal function affects local magnesium homeostasis and thus contributes to the physicochemical composition of microcalcification in atherosclerotic patients.

Compositional Analysis of Coronary Artery Calcification in Dialysis Patients in vivo by Dual‐Energy Computed Tomography Angiography

“…Several studies have reported the composition of vascular calcifications. Schmid, et al studied the mineral deposits excised from atherosclerotic thoracic and abdominal aortas at autopsy.…”

Elemental vs. phase composition of breast calcifications

“…The presence of whitlockite is therefore an indicator of the local magnesium concentration at the time of mineralisation, rather than the time of sampling 39 . In precipitation experiments where there are both carbonate and magnesium ions in solution, it has also been observed that lower pH leads to less magnesium incorporation into the apatite lattice for a given magnesium concentration in the solution 40 .…”

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

“…By contrast, media calcification can occur in arteries of any size, is a typical age-related process and has been associated with increased stiffness and reduced cushioning function [17,18]. In patients with diabetes mellitus and/or chronic kidney disease, both forms of calcification are present but are usually not distinguished in epidemiological studies, since non-ambiguous discrimination is hardly achievable unless vessel specimens for histological evaluation are available [19]. Although the initial events leading to either intima or media calcification differ, both reflect an active and highly regulated process closely resembling endochondral and/or intramembraneous bone formation.…”