What is calcific uremic arteriolopathy (CUA)?
Calcific uremic arteriolopathy, or calciphylaxis is a rare but life-threatening syndrome characteristically occurring in individuals with ESRD, but has been described in patients with normal kidney function and calcium/phosphate metabolism.
Calcific uremic arteriolopathy generally presents as excruciatingly painful eschars on the lower limbs but may affect other sites, including the abdominal wall, breasts, and penis, and only rarely the face or upper extremities. The syndrome typically begins with dysesthesia, followed by the development of erythema resembling livedo reticularis, and progression to frank ulceration. There may be palpable deposits of calcium subcutaneously.
The lesions are intensely painful, and the surrounding tissue may be pruritic. The lesions have been proposed to occur at sites of adipose tissue where diminished blood flow contributes to hypoxia.
Major risk factors for CUA include:
• Female gender
• Diabetes mellitus
• Obesity
• Malnutrition
• Elevated serum phosphate
• Warfarin
The underlying pathology is vascular calcification. The calcification was historically assumed to be a passive event caused by deranged calcium and phosphate metabolism; however, this calcification is an actively regulated process. Elevated phosphate levels has been regarded as one of the most important factors in initiating CUA, with persistent hyperphosphatemia and hypercalcemia promoting vascular mineralization. Defects in a number of inhibitors of calcification, including matrix GLA protein and fetuin, play a causative role. Most patients with CUA die from complications of wound infections. Therapy should be focused on wound management and controlling serum phosphate levels. Parathyroidectomy is controversial and is generally not recommended unless PTH levels are markedly elevated (>900 ng/mL). Aggressive dialysis, nutrition, and non-calcium-containing phosphate binders are the mainstay of therapy. Some studies have demonstrated anecdotal response to sodium thiosulfate. It is unclear if calcimimetics or bisphosphonates are beneficial.
