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| Year : 2009 | Volume
: 20
| Issue : 6 | Page : 1065-1068 |
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| Use of sodium thiosulfate in the treatment of calciphylaxis |
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Carlos G Musso1, Paula Enz2, Flavia Vidal3, Rodolfo Gelman4, Aldana Lizarraga1, Luis Di Giuseppe5, Alicia Kowalczuk2, Leonardo Garfi5, Ricardo Galimberti2, Luis Algranati1
1 Department of Nephrology, Hospital Italiano de Buenos Aires, Argentina
2 Department of Dermatology, Hospital Italiano de Buenos Aires, Argentina
3 Department of Toxicology, Hospital Italiano de Buenos Aires, Argentina
4 Department of Endocrinology, Hospital Italiano de Buenos Aires, Argentina
5 Department of Farmacy, Hospital Italiano de Buenos Aires, Argentina
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| Date of Web Publication | 27-Oct-2009 |
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 Abstract | | |
Calciphylaxis is an infrequent but severe entity found in chronic dialysis patients. Its clinical pattern consists of tissue ischemia with itchy and painful subcutaneous nodules and plaques, most often located on the abdomen, buttocks, thighs and/or legs. These injuries evolve to extensive superficial necrosis of the skin overlying the panniculitis, with ulceration, overinfection and consequent sepsis. Current treatment modalities used to counteract this pathology are not entirely effective. A new treatment reported for calciphylaxis, is the use of intravenous sodium thiosulfate. This inorganic salt is already used in the treatment of intoxication caused by cyanide, in patients with calcific nephrolithiasis and tumoral calcinosis, with very good and safe results. We herewith report a case of calciphylaxis that was cured using intravenous sodium thiosulphate treatment.
How to cite this article:
Musso CG, Enz P, Vidal F, Gelman R, Lizarraga A, Giuseppe LD, Kowalczuk A, Garfi L, Galimberti R, Algranati L. Use of sodium thiosulfate in the treatment of calciphylaxis. Saudi J Kidney Dis Transpl 2009;20:1065-8 |
How to cite this URL:
Musso CG, Enz P, Vidal F, Gelman R, Lizarraga A, Giuseppe LD, Kowalczuk A, Garfi L, Galimberti R, Algranati L. Use of sodium thiosulfate in the treatment of calciphylaxis. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2021 Jan 24];20:1065-8. Available from: https://www.sjkdt.org/text.asp?2009/20/6/1065/57265 |
| Introduction | |  |
Calciphylaxis, also called uremic calciphying arteriolopathy, is an infrequent (1-4%) complication in chronic dialysis patients. The etiology of this entity still remains unclear and it consists of an inflammation of the skin with edema, erhythema and pain, which may evolve to extensive superficial necrosis of the skin overlying the panniculitis, with ulceration and scar formation. Its clinical pattern consists of tissue ischemia with itchy and painful subcutaneous nodules and plaques, most often located on the abdomen, buttocks, thighs and/or legs. [1],[2]
The diagnosis is confirmed when there is a calcification of the middle layer of the small arteries of the dermis in the affected areas, when skin biopsy is performed. A mild lymphohistiocytic inflammatory reaction is usually observed in the area. [1]
This entity is associated with a high morbidity and mortality (45-89%) depending on the location of the injury and its type (worse prognosis in ulcerated and proximal injury). Sepsis secondary to super-infection of the ulcerated lesions is the main cause of death in this patients. [3]
Numerous risk factors have been identified including: female gender, obesity, diabetes mellitus, malnutrition, hypoalbuminemia, hyper- phosphatemia, hypercalcemia, high calciumphosphorus product, secondary hyperparathyroidism, hypercoagulability states and treatment with vitamin D and calcium-based phosphate binders. [2],[3],[4]
Some treatment modalities used to counteract this pathology are phosphate binders without calcium, parathyroidectomy in patients with severe secondary hyperparathyroidism, low calcium dialysis solutions and corticosteroids. However, none of these treatments are entirely effective. [3]
A new option reported for treating calciphylaxis is the use of intravenous sodium thiosulfate. [5],[6],[7],[8] This inorganic salt is already being used in the treatment of cyanide toxicity, calcific nephrolithiasis and tumoral calcinosis, with very good and safe results. The pentahydrated sodium thiosulfate (Na2S2O3. 5H2O) dissolves the deposits of calcium, producing a salt of thiosulfate of calcium (S2O3Ca), which is extremely soluble and can be removed by dialysis. [9],[10],[11]
We herewith report a case of calciphylaxis that was cured with the use of intravenous sodium thiosulfate.
| Case Report | | |
A 57-year-old-female, Caucasian, with a history of diabetes mellitus (type II), arterial hypertension, morbid obesity and chronic renal failure of unknown origin was commenced on peritoneal dialysis in December 2002. After three years of treatment, she lost her peritoneal catheter due to fungal peritonitis and following that, she was started on hemodialysis using an arterio-venous fistula as vascular access.
While on dialysis, the patient had anemia (hematocrit: 22%) refractory to treatment with subcutaneous erythropoietin (12,000 IU/week) and secondary hyperparathyroidism [intact parathyroid hormone 1440 pg/mL: (normal range: 150-300 pg/mL)]. The serum calcium was 9 mg/dL, serum phosphorus was 8 mg/dL and the Ca Χ P product was high at 72 mg/dL, which was refractory to treatment with phosphorus binders (2-3 g/day of aluminum hydroxide).
The patient's persistent hyperphosphatemia did not allow for treatment of the secondary hyperparathyroidism with calcitriol and because of that a subtotal parathyroidectomy was planned. Before parathyroidectomy could be performed, she developed a purple, subcutaneous, non-ulcerous and painful nodule in the left inguinal region [Figure 1]. A diagnosis of uremic calciphying arteriolopathy was confirmed by skin biopsy. After that, a subtotal parathyroidectomy was performed. However, despite normalization of serum parathormone level to 200 pg/mL and Ca Χ P product to 33 mg/dL, the calciphylaxis worsened. Other nodules appeared on the thighs, legs and abdominal fat; also, ulcerated injuries developed in the right flank affecting the subcutaneous cellular tissue without compromising the underlying muscle [Figure 2],[Figure 3]. On examination, the lesions were tender and hard stony plaques were felt. The pain worsened characteristically during the dialysis sessions.
In order to reduce the pain, several analgesics such as diclofenac (145 mg/day) and tramadol (100 mg/day) were used without much improvement. Since sodium thiosulfate had recently been proposed as an effective and safe new treatment for calciphylaxis, this therapy was proposed to the patient who accepted the proposal.
Treatment with intravenous sodium thiosulfate was commenced at a dose of 25 g (100 mL of a solution at 25% of sodium thiosulfate), administered immediately post-dialysis, three times per week. Starting from the second application it was necessary to reduce the dose by half, due to the occurrence of hypotension. Three months following the initiating of sodium thiosulfate, the injuries began to improve and concomitantly the original stony subcutaneous plaques became a group of broken pieces and they melted progressively until the skin retook its normal texture. Since we wanted to avoid infection of the ulcers, we added local dressings with calcium alginate to the intravenous treatment and local application of an ointment containing a combination of gentamicin and acetamidohexanoic acid. After six months, the lesions continued to heal slowly and progressively, and decreased in size by 80%. The lesions which were not ulcerated disappeared completely.
After ten months of treatment, all her lesions had completely healed [Figure 4],[Table 1].
| Discussion | | |
Our patient presented with several of the risk factors for developing calciphylaxis such as obesity, diabetes mellitus, secondary hyperparathyroidism, high calcium-phosphorus product, and proximal skin caciphylaxis injuries. Moreover, she was on treatment with calcium-based salts. [3] Given the high mortality of calciphylaxis, the lack of a clearly effective treatment and the existence of recent reports about the potential benefits of intravenous sodium thiosulfate, this treatment was begun.
The thiosulfate of sodium is an inorganic pentahydrated salt (Na2S2O5.5H2O) with a molecular weight of 248.2. It is poorly absorbed from the digestive tract. When administered through the intravenous route, it is distributed to the whole extracellular fluid, and is quickly excreted in the urine. Except causing osmotic alterations, the thiosulfate is not very toxic. High doses through the oral route have a cathartic effect. It has been used for more than 100 years in the treatment of intoxication with cyanide. Additionally, it seems to be a safe treatment in dialysis patients. [9],[10],[11] We hypothesize that this drug could act producing a salt of thiosulfate of calcium (S2O3Ca), which is extremely soluble and can get removed by dialysis.
Sodium thiosulphate has also been used successfully through the intravenous route in the mobilization of deposits of calcium in patients with tumoral calcinosis, in treatments that have lasted from 6 to 24 months. [5] We observed a similar phenomenon when the stony hard plaques melted progressively during the thiosulfate treatment.
The dose of sodium thiosulfate used in the different clinical cases was 25 g (100 mL of a solution at 25% of sodium thiosulfate) three times per week immediately after dialysis. [5],[6],[7],[8] We began treatment with the same dose, but since in the second infusion, the patient developed hypotension, the dose was reduced by 50%. No other clinical or biochemical complications were observed.
We also would like to point out that the current terminology, namely "calciphylaxis" may lead to misinterpretations. On one hand, the name calciphylaxis might indicate a hypersensitivity to calcium; this is not the pathophysiological mechanism of this disease. On the other hand, its other name uremic calcifying artheriolopathy is a term that can create confusion because this entity is not exclusive to uremic patients, and can occur in oncology patients who have normal kidney function. [1] Perhaps; calcifying artheriolopathy could be a better terminology.
| Conclusion | | |
The use of intravenous sodium thiosulphate seems to be an effective and safe treatment for calciphylaxis associated with chronic renal disease.
| References | | |
| 1. | Bondi E, Margolis D, Lazarus G. Panniculitis. In: Freedberg I, Eisen A, Wolff K, Austen K, Goldsmith L, Katz S, Fitzpatrick T,(eds): Fitzpatrick΄s Dermatology in general medicine. New York. Mc Graw-Hill 1999:1275-88  |
| 2. | Goodman WG, London G, Amann K, et al. Vascular calcification in chronic kidney disease. Am J Kidney Dis 2004;43(3):572-9. |
| 3. | Fine A, Zacharias J. Calciphylaxis is usually nonulcerating: Risk factors, outcome and therapy. Kidney Int 1002;61:2210-7. |
| 4. | Rauf Mazhar A, Johnson RJ, Gillen D, et al. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int 2001;60:324-32. |
| 5. | Papadakis JT, Patrikarea A, Digenis GE, et al. Sodium thiosulfate in the treatment of tumoral calcifications in a hemodialysis patients with-out hyperparathyroidism. Nephron 1996;72: 308-12. [PUBMED] |
| 6. | Cicone JS, Petronis JB, Embert CD, et al. Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am J Kidney Dis 2004;43(6): 1104-8. |
| 7. | Brucculeri M, Cheigh J, Bauer G, et al. Long-term intravenous sodium thiosulfate in the treat-ment of a patient with calciphylaxis. Semin Dial 2005;18(5): 431-4. |
| 8. | Guerra G, Shah RC, Ross EA. Rapid resolution of calciphylaxis with intravenous sodium thiosulfate and continous venovenous haemofiltration using low calcium replacement fluid: case report. Pharmacol Ther 1984;35:419-25. |
| 9. | Yatzidis H. Successful sodium thiosulphate treatment for recurrent calcium urolithiasis. Clin Nephrol 1985;23(2):63-7. |
| 10. | Yatzidis H, Agroyannis B. Sodium thiosulfate treatment of soft-tissue calcifications in patients with end-stage renal disease. Peritoneal Dial Bull 1987;7(4):250-2. |
| 11. | Lacy C, Armstrong L, Goldman M, Lance L. Drug Information Handbook International. Hudson. Lexi-Comp 2004 :1399-1400. |
Correspondence Address:
Carlos G Musso
Department of Nephrology, Hospital Italiano de Buenos Aires
Argentina
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PMID: 19861872 
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1] |
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