Abstract
Calcific uremic arteriolopathy (CUA; also known as calciphylaxis) is a life-threatening condition observed mostly in patients on dialysis. The key histopathologic features of CUA include media calcification of small arteries, associated with endovascular fibrosis and thrombosis. Several risk factors for CUA are related to disturbances in bone and mineral metabolism; current treatments largely aim to normalize these disturbances by lowering serum calcium phosphate concentration and thereby preventing, or even reversing, calcium phosphate oversaturation, precipitation and, finally, calcification. Administration of sodium thiosulfate, which sequesters calcium ions to form highly soluble calcium thiosulfate complexes, can prevent calcium phosphate precipitation. As randomized controlled studies on sodium thiosulfate are lacking, this Perspectives article focuses on case reports and case series; in these reports the compound seemed to be effective and was not associated with serious short-term adverse events. Large clinical trials to evaluate the efficacy and long-term safety of sodium thiosulfate are clearly warranted.
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References
Rogers, N. M., Teubner, D. J. & Coates, P. T. Calcific uremic arteriolopathy: advances in pathogenesis and treatment. Semin. Dial. 20, 150–157 (2007).
Nigwekar, S. U., Wolf, M., Sterns, R. H. & Hix, J. K. Calciphylaxis from nonuremic causes: a systematic review. Clin. J. Am. Soc. Nephrol. 3, 1139–1143 (2008).
Angelis, M., Wong, L. L., Myers, S. A. & Wong, L. M. Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery 122, 1083–1089 (1997).
Fischer, A. H. & Morris, D. J. Pathogenesis of calciphylaxis: study of three cases with literature review. Hum. Pathol. 26, 1055–1064 (1995).
Au, S. & Crawford, R. I. Three-dimensional analysis of a calciphylaxis plaque: clues to pathogenesis. J. Am. Acad. Dermatol. 47, 53–57 (2002).
Schlieper, G., Westenfeld, R., Brandenburg, V. & Ketteler, M. Inhibitors of calcification in blood and urine. Semin. Dial. 20, 113–121 (2007).
Schäfer, C. et al. The serum protein α2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J. Clin. Invest. 112, 357–366 (2003).
Cranenburg, E. C. et al. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J. Vasc. Res. 45, 427–436 (2008).
Coates, T. et al. Cutaneous necrosis from calcific uremic arteriolopathy. Am. J. Kidney Dis. 32, 384–391 (1998).
Brandenburg, V. M., Floege, J. & Ketteler, M. Calcific uremic arteriolopathy (CUA): international collaborative calciphylaxis network (ICCN) [abstract]. Presented at Renal Week 2008, ASN: SA-PO2843 (2008).
Hayden, M. R., Tyagi, S. C., Kolb, L., Sowers, J. R. & Khanna, R. Vascular ossification-calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis-calcific uremic arteriolopathy: the emerging role of sodium thiosulfate. Cardiovasc. Diabetol. 4, 4 (2005).
Weenig, R. H. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B. J. Am. Acad. Dermatol. 58, 458–471 (2008).
Fine, A. & Fontaine, B. Calciphylaxis: the beginning of the end? Perit. Dial. Int. 28, 268–270 (2008).
Hayden, M. R., Goldsmith, D., Sowers, J. R. & Khanna, R. Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate. Int. Urol. Nephrol. 40, 443–451 (2008).
Raymond, C. B. & Wazny, L. D. Sodium thiosulfate, bisphosphonates, and cinacalcet for treatment of calciphylaxis. Am. J. Health Syst. Pharm. 65, 1419–1429 (2008).
Pasch, A. et al. Sodium thiosulfate prevents vascular calcifications in uremic rats. Kidney Int. 74, 1444–1453 (2008).
Brucculeri, M., Cheigh, J., Bauer, G. & Serur, D. Long-term intravenous sodium thiosulfate in the treatment of a patient with calciphylaxis. Semin. Dial. 18, 431–434 (2005).
Bodell, M. A., Deng, J. & Spector, D. A. Sodium thiosulfate (STS) prevents vascular calcification (VC) in rats with adenine-induced kidney disease [abstract]. Presented at Renal Week 2008, ASN: F-PO1822 (2008).
Cicone, J. S., Petronis, J. B., Embert, C. D. & Spector, D. A. Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am. J. Kidney Dis. 43, 1104–1108 (2004).
Guerra, G., Shah, R. C. & Ross, E. A. Rapid resolution of calciphylaxis with intravenous sodium thiosulfate and continuous venovenous haemofiltration using low calcium replacement fluid: case report. Nephrol. Dial. Transplant. 20, 1260–1262 (2005).
Araya, C. E., Fennell, R. S., Neiberger, R. E. & Dharnidharka, V. R. Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults. Clin. J. Am. Soc. Nephrol. 1, 1161–1166 (2006).
Hayden, M. R., Kolb, L. G. & Khanna, R. Calciphylaxis and the cardiometabolic syndrome. J. Cardiometab. Syndr. 1, 76–79 (2006).
Mataic, D. & Bastani, B. Intraperitoneal sodium thiosulfate for the treatment of calciphylaxis. Ren. Fail. 28, 361–363 (2006).
Meissner, M. et al. Sodium thiosulphate as a promising therapeutic option to treat calciphylaxis. Dermatology 212, 373–376 (2006).
Ackermann, F. et al. Sodium thiosulfate as first-line treatment for calciphylaxis. Arch. Dermatol. 143, 1336–1337 (2007).
Baker, B. L., Fitzgibbons, C. A. & Buescher, L. S. Calciphylaxis responding to sodium thiosulfate therapy. Arch. Dermatol. 143, 269–270 (2007).
Li, J. Z. & Huen, W. Images in clinical medicine. Calciphylaxis with arterial calcification. N. Engl. J. Med. 357, 1326 (2007).
Kyritsis, I. et al. Combination of sodium thiosulphate, cinacalcet, and paricalcitol in the treatment of calciphylaxis with hyperparathyroidism. Int. J. Artif. Organs 31, 742–744 (2008).
Musso, C. G. et al. Oral sodium thiosulfate solution as a secondary preventive treatment for calciphylaxis in dialysis patients. Saudi J. Kidney Dis. Transpl. 19, 820–821 (2008).
Soni, S. & Leslie, W. D. Bone scan findings in metastatic calcification from calciphylaxis. Clin. Nucl. Med. 33, 502–504 (2008).
Subramaniam, K., Wallace, H., Sinniah, R. & Saker, B. Complete resolution of recurrent calciphylaxis with long-term intravenous sodium thiosulfate. Australas. J. Dermatol. 49, 30–34 (2008).
Tindni, A., Gaurav, K. & Panda, M. Non-healing painful ulcers in a patient with chronic kidney disease and role of sodium thiosulfate: a case report. Cases J. 1, 178 (2008).
Meade, D., Lacson, E., Wang, W. & Lazarus, M. Sodium thiosulfate therapy for calciphylaxis in hemodialysis patients [abstract]. Presented at Renal Week 2008, ASN: SA-PO2775 (2008).
Hackett, B. C., McAleer, M. A., Sheehan, G., Powell, F. C. & O'Donnell, B. F. Calciphylaxis in a patient with normal renal function: response to treatment with sodium thiosulfate. Clin. Exp. Dermatol. 34, 39–42 (2009).
Riegert-Johnson, D. L., Kaur, J. S. & Pfeifer, E. A. Calciphylaxis associated with cholangiocarcinoma treated with low-molecular-weight heparin and vitamin K. Mayo Clin. Proc. 76, 749–752 (2001).
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Schlieper, G., Brandenburg, V., Ketteler, M. et al. Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol 5, 539–543 (2009). https://doi.org/10.1038/nrneph.2009.99
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DOI: https://doi.org/10.1038/nrneph.2009.99
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