Abstract 17743: Calcific Uremic Arteriolopathy is Characterized by Increased Arteriolar Bone Morphogenetic Protein Signaling
Background: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a subcutaneous vasculopathy associated with calcification of the medial layer of arterioles leading to thrombosis and skin necrosis. CUA is almost exclusively seen in patients with end-stage chronic kidney disease and is usually fatal. Bone morphogenetic protein (BMP) signaling plays an important role in the calcification of large- and mid-sized arteries. We hypothesized that BMP signaling is increased in the subcutaneous arterioles of patients with CUA.
Methods: Formalin-fixed, paraffin-embedded, skin biopsies were obtained from ten patients with CUA and four patients without the disease. Vascular calcification was assessed using Von Kossa histochemical staining. To detect evidence for activation of BMP signaling, tissue sections were stained with antibodies directed against phosphorylated SMADs 1 and 5 (p-SMAD1/5).
Results: Von Kossa staining detected calcification in the medial layer of arterioles in the skin tissue specimens from all patients with CUA. Robust p-SMAD1/5 staining was detected adjacent to the arteriolar calcification in all 10 CUA patients. Neither calcification nor p-SMAD1/5 immunoreactivity was detected in arterioles in control samples (see Figure).
Conclusions: The results of this study provide evidence that increased BMP signaling contributes to the pathogenesis of CUA. Inhibition of BMP signaling is a promising approach to the treatment of this life-threatening disease.
Author Disclosures: P. Jiramongkolchai: None. S.U. Nigwekar: Research Grant; Modest; Sanofi-Aventis. Honoraria; Modest; Sanofi-Aventis. Consultant/Advisory Board; Modest; Becker Professional Education. R.M. Nazarian: None. R. Malhotra: Consultant/Advisory Board; Modest; Happtique, Inc. K.D. Bloch: Research Grant; Modest; Merck, Bayer. Honoraria; Modest; Merck, Bayer. Consultant/Advisory Board; Modest; American Heart Association. R.I. Thadhani: Research Grant; Modest; Kaneka Corporation. Honoraria; Modest; Fresenius Medical Care North America, Shire Human Genetics, Biogen, ThermoFisher, Diasorin. Ownership Interest; Modest; Aggamin LLC. Consultant/Advisory Board; Modest; Aggamin LLC. D.B. Bloch: None.
- © 2014 by American Heart Association, Inc.