Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis.

To the Editor: Calciphylaxis is a syndrome of microvascular calcification and thrombosis leading to painful purpuric skin lesions that progress to necrotic ulcers. Calciphylaxis occurs primarily in patients with ESRD, for which its prevalence has been estimated at 1% annually, and carries a high mortality rate. Increasingly, sodium thiosulfate (STS) is used off-label for treating calciphylaxis. The STS mechanism of action in this condition is unknown. One postulated mechanism is by binding to calcium phosphate salts to form soluble calcium thiosulfate, though additional antioxidant, vasodilatory, and direct inhibitory actions on vascular calcification have been proposed. Dosing of STS, which contains 12.7 mEq/g of sodium and thiosulfate, is empirical and typically 12.5 or 25 g is given during the final 30 to 60 minutes of a hemodialysis (HD) session. A retrospective study showed that 73% of patients treated for calciphylaxis with STS had clinical improvement, with 26% having complete resolution of skin lesions. Case reports have described an association of STS with increased anion gap. The mechanism is unknown but has been postulated to be due to oxidation of thiosulfate by the liver or intestinal bacteria to sulfate, which may be enhanced in ESRD due to diminished medication clearance. A retrospective survey study of an outpatient HD cohort treated with STS revealed a mean increase in anion gap of w3 mmol/L. However, no existing studies report individual variability in response to STS, and a dose-response effect of STS on anion gap elevation has not been established. To this end, we report our institutions’ experience with the effect of STS on anion gap. Using an electronic database, we identified all patients with a diagnosis of calciphylaxis who were treated with STS at Massachusetts General Hospital and Brigham and Women’s Hospital between January 2005 and December 2014. For each case, all laboratory values were collected within 30 days prior to initiation of STS and through 30 days while on treatment with STS, or until