Calciphylaxis: from the disease to the diseased

Calciphylaxis, or calcific uremic arteriolopathy, is a vascular ossification–calcification disease involving cutaneous or visceral arterioles, with ischemic damage of the surrounding tissues, usually in the setting of chronic kidney disease. Pathogenesis is still unclear and probably comprises the participation of vascular smooth muscle cells, endothelial cells and macrophages surrounded by a uremic and/or pro-calcifying environment. According to the original concept of calcific uremic arteriolopathy coined by Hans Selye, risk factors may be divided into sensitizers and challengers and their knowledge is useful in clinical practice to pre-emptively identify both uremic and non-uremic ‘at risk’ patients and guide treatment. Systemic calcific uremic arteriolopathy is a rarity. Cutaneous calcific uremic arteriolopathy is more frequent and clinically presents as a first phase of cutaneous hardening and erythema, followed by a second phase of ulcerations and scars; these two phases are probably associated with the initial development of arteriolar lesion and tissue ischemic damage, respectively. Clinical history, physical examination, laboratory analysis, histology and imaging are the main tools to exclude important differential diagnoses and obtain a definitive diagnosis. Treatment is generally unrewarding and consists of rigorous control of comorbid conditions, anti-oxidant, anti-inflammatory and antithrombotic strategies, avoidance of iatrogeny and wound and pain management. Prognosis remains poor in terms of morbidity and mortality. Efforts should be made towards a greater awareness of calcific uremic arteriolopathy, development of better therapies and improvement of clinical outcomes.