Dialysis Rounds
A Dialysis Case 
Presentation and Discussion
Edited by Roger A. Rodby : Long‐Term Intravenous Sodium Thiosulfate in the Treatment of a Patient with Calciphylaxis

Abstract

Calciphylaxis is a disabling and life-threatening complication that primarily affects patients who are dialysis dependent. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels, which results in necrotizing, nonhealing ulcers. The development of these lesions portends a grim prognosis, as they are often accompanied by severe and sometimes fatal infectious complications. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe an anuric hemodialysis patient who developed severe calciphylaxis that proved refractory to conventional treatment. Following extensive debridement of several wounds, intravenous sodium thiosulfate was utilized as an adjunctive therapy four times a week. Within 6 months, excellent wound healing ensued as well as a dramatic improvement in the lesions that were not previously resected. Aside from occasional nausea, these treatments were well tolerated, despite the development of an anion gap metabolic acidosis. After 34 months of continued treatment the patient remains free from disease recurrence and has demonstrated no untoward effect of prolonged therapy. In an effort to delineate the pharmacokinetics of this drug in a hemodialysis patient, serum thiosulfate levels were obtained 15 minutes after infusion as well as before and after subsequent dialysis treatments. Consistent with prior studies in anuric canines, we found measurable quantities of the drug more than 50 hours after treatment, in addition to a markedly elevated half life of 478 minutes. However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients.

Evolution of Treatment Strategies for Calciphylaxis

“…area under the curve) until its removal by the subsequent dialysis session. Typically, 25 g is given intravenously over 1 h after each of the thrice weekly high-flux hemodialysis treatments [14,15,16]. We feel it is important that the dose be adjusted for dialysis clearance when utilizing more intense or frequent intermittent treatments or for continuous modalities [17] (table 2).…”

Sodium Thiosulphate: A New Way of Treatment for Calciphylaxis?

“…In an anuric patient this way of elimination seems to be reversed and the serum half-life much increased, which might be an important precondition for the mechanism of chelating calcium from precipitated calcium salts in the vessels. Brucculeri et al [27] could convincingly show that in their anuric patient the serum half-life of STS was 478 min compared to 15 min in healthy controls. Concerning these results, they postulated that the primary way of elimination of STS is biliary secretion.…”

“…In all described cases up to now there has been no evidence of recurrence of disease or severe side effects of the treatment. The only adverse drug reactions were described by Brucculeri et al [27], reporting occasional mild nausea and sometimes a slight emesis. In addition, these authors reported that the intravenous application of STS had an impact on the patients’ acid-base status, developing anion gap metabolic acidosis, which could be compensated by using a high bicarbonate dialysate.…”

“…Following this extraordinary success, different groups administered STS as an important element of the treatment strategy of calciphylaxis, normally in doses of 5–25 g intravenously after or during hemodialysis [26,27,28,29]. One author applied STS intraperitoneally [30].…”

Multi-Modal Treatment Of Calciphylaxis With Sodium-Thiosulfate, Cinacalcet And Sevelamer Including Long-Term Data

“…Two new principles of treatment have recently emerged: (i) control of hyperparathyroidism by treatment with calcium sensitizers (cinacalcet) [23,24] , and (ii) improving solubility of calcium and phosphate by sodium thiosulfate (STS) [25,26]. This drug, known as antidote in cyanide intoxication, was first used to prevent recurrence of calcium containing stones of the urinary tract [27], then in tumoral calcinosis [28] and, more recently, has been used in calciphylaxis [29,30].…”