Sodium Thiosulfate Treatment for Calcific Uremic Arteriolopathy in Children and Young Adults

Abstract

In adult patients with ESRD, calcific uremic arteriolopathy (CUA) is an uncommon but life-threatening complication. No effective therapy exists, although anecdotal case reports highlight the use of sodium thiosulfate (STS), a calcium-chelating agent with antioxidant properties. CUA is rare in children, and STS use has not been reported. The objective of this study was to determine the influence of STS treatment on three patients with CUA in a pediatric chronic dialysis unit. The patients were between 12 and 21 yr of age; two were male; and primary diagnoses were obstructive uropathy, renal dysplasia, and calcineurin nephrotoxicity. Time from ESRD to CUA diagnosis was 1, 9, and 20 yr. Diagnosis was made by tissue biopsy and three-phase bone scan. Pain was the presenting symptom. Initial treatment included discontinuation of calcitriol and use of non-calciumbased phosphate binders and low-calcium dialysate concentration. STS dosage was 25 g/1.73 m 2 per dose intravenously after each hemodialysis session. For optimization of removal of calcium deposits, patient three received a combination of STS and continuous venovenous hemofiltration for the first 10 d. All patients demonstrated rapid pain relief. Within weeks, skin induration and joint mobility of the extremities improved. Radiographic evidence of reduction in the calcium deposits occurred within 3 mo of initiation of STS. The only complication was prolonged QT interval in one patient as a result of hypocalcemia, who was resolved by use of a higher dialysate calcium concentration. STS seems well tolerated in children and young adults with CUA and has mild adverse effects. For determination of its efficacy, optimum dosage, duration of therapy, and dialysis modality, controlled trials are needed.

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

“…Sodium thiosulfate (STS, Na 2 S 2 O 3 ⅐5H 2 O, MW 248 g) is an old drug used for decades as an antidote against cyanide poisoning (3), because STS supplements the cyanide-detoxifying enzyme rhodanese (4,5), which is part of the endogenous thiosulfate (TS) synthesis pathway (6). Recently, STS has been prescribed for the treatment of soft-tissue calcifications in patients with calciphylaxis (7)(8)(9)(10)(11)(12). Furthermore, systematic studies in rats (13) and humans (14) have investigated the effect of STS on aortic and coronary artery calcifications.…”

Successful treatment of calcific uremic arteriolopathy in a pediatric dialysis patient

“…Therapy with STS was initiated 3 weeks after diagnosis, at a dose of 25 g/1.73 m 2 , with thrice-weekly administration, as previously recommended [1]. The patient's pain was reduced rapidly with the initiation of STS infusions.…”

“…It is a rapidly progressive condition, resulting in painful necrosis of the skin and subcutaneous tissues. These areas can become ulcerated and infected, which often necessitate limb amputation [1,2]. Once considered a very rare condition, CUA now has reported prevalence rates as high as 4.1% in adults with end-stage-renal disease (ESRD).…”

“…Increased awareness, along with the extensive use of calcium-containing phosphate binders and vitamin D analogues, is likely responsible for the increased prevalence of this disease [3]. Treatment of CUA remains controversial, with many experimental approaches currently in practice, including sodium thiosulfate (STS) and hyperbaric oxygen (HBO) [1,2]. Unfortunately, the prognosis of CUA remains poor, and mortality rates are highgreater than 80%.…”

Measuring Plasma Conductivity to Detect Sodium Load in Hemodialysis Patients

“…S odium thiosulfate treatment has been proposed to treat calcific uremic arteriolopathy in hemodialysis patients (1)(2)(3)(4) and recently for nephrogenic systemic fibrosis (5). The dose is 25 g/1.73 m 2 per hemodialysis session during the last 60 min.…”