Sodium thiosulfate, bisphosphonates, and cinacalcet for treatment of calciphylaxis

Abstract

Purpose: The use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis in adults with chronic kidney disease (CKD) is discussed.

Summary: Calciphylaxis, generally characterized by extraosseous calcification of soft tissues, typically occurs in patients with stage 4 or 5 CKD. Very little data are available regarding the treatment of calciphylaxis. The role of elevated calcium and phosphate concentrations and hyperparathyroidism as risk factors for calciphylaxis has led clinicians to explore therapies that modify these factors, including sodium thiosulfate, bisphosphonates, and cinacalcet. Sodium thiosulfate has been shown to produce clinical improvement of calciphylaxis lesions. Bisphosphonates have been shown to be effective in animal models of calciphylaxis, and the mechanism of action is believed to be due to inhibition of macrophages and local proinflammatory cytokines and binding to calcified vascular smooth muscle cells to inhibit further arterial calcification. Cinacalcet, a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor on the parathyroid gland to calcium, is believed to decrease serum parathyroid hormone levels and stabilize calcium and phosphate concentrations. Cinacalcet has been associated with improved pain control and ulcer healing. Cases describing the use of combination therapy with cinacalcet and sodium thiosulfate for the treatment of calciphylaxis have been published, but the positive effect on wound healing is difficult to attribute to a single drug.

Conclusion: Evidence for the treatment of calciphylaxis with pharmacotherapeutic interventions is limited to case reports. Further research is necessary to fully describe the optimal use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis, including their pharmacokinetics in adults with CKD, optimal dosing strategies, and duration of therapy.