; for the Groupe Angio-Dermatologie of the French Society of Dermatology IMPORTANCE Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described. OBJECTIVES To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. DESIGN, SETTING, AND PARTICIPANTS A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. MAIN OUTCOMES AND MEASURES Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emissionscanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. RESULTS Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium-phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. CONCLUSIONS AND RELEVANCE Calcific uremic arteriolopathy-related skin calcifications were exclusively composed of pure calcium-phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels' appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO particles contribute to the granuloma formation, whereas CaCO deposits are related to the granuloma biology. However, the significance of the association between SiO deposits and sarcoidosis is still disputed.