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Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate

  • Nephrology - Review
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Abstract

Calciphylaxis–calcific uremic arteriolopathy, is a serious disorder of arteriolar calcification of the arteriole media and is associated with endovascular fibrosis and thrombosis in subcutaneous adipose tissue. It frequently results in severe ischemia, intense pain, and tissue necrosis with nonhealing skin ulcerations. It usually occurs in chronic kidney disease and especially in patients requiring renal replacement therapy. It is associated with a very high mortality rate, and the number of reports and reviews seemed to have increased over the past 5 years. Advances in therapy and salvaging patients from this high mortality risk have recently been reported with the use of sodium thiosulfate. The new application for this old drug used to treat cyanide poisoning and recently preventing neurotoxic effects resulting in hearing loss in those patients with head and neck cancer receiving cisplatin and carboplatin therapy are discussed. Recently, multiple case reports have demonstrated that sodium thiosulfate therapy has resulted in rapid pain relief, healing of skin ulcerations, and prevention of high mortality risk. This emerging treatment and its success are relatively unknown to many physicians. The purpose of this report is to share with others the emerging role of sodium thiosulfate and its new application as a treatment option to be used in combination with other treatment modalities for calciphylaxis–calcific uremic arteriolopathy. Indeed, as with any new treatment this emerging therapy should be studied in greater detail, but this old drug seems to have a new life in the hands of treating physicians.

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References

  1. Virchow R (1855) Kalk Metastasen. Arch Pathol Anato 8:103–113

  2. Virchow R (1863) Cellular pathology: as based upon physiological and pathological histology (trans: Chance F (1971)). An unabridged and unaltered republication of the English translation originally published in Dover, New York, pp 404–408

  3. Shanahan CM (2005) Mechanisms of vascular calcification in renal disease. Clin Nephrol 63:146–157

    PubMed  CAS  Google Scholar 

  4. Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119

    Article  PubMed  CAS  Google Scholar 

  5. Klausen KP, Scharling H, Jensen JS (2006) Very low level of microalbuminuria is associated with increased risk of death in subjects with cardiovascular or cerebrovascular diseases. J Intern Med 260:231–237

    Article  PubMed  CAS  Google Scholar 

  6. Tonelli M, Sacks F, Pfeffer M et al (2005) Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633

    Article  PubMed  CAS  Google Scholar 

  7. McCullough PA, Sandberg KR, Dumler F, Yanez JE (2004) Determinants of coronary vascular calcification in patients with chronic kidney disease and end-stage renal disease: a systematic review. J Nephrol 17(2):205–215

    PubMed  Google Scholar 

  8. Wang MC, Tsai WC, Chen JY, Huang JJ (2005) Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis 45:494–501

    Article  PubMed  Google Scholar 

  9. Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM (2007) Exploring the biology of vascular calcification in chronic kidney disease: what’s circulating? Kidney Int (Epub ahead of print)

  10. Selye H (1962) Calciphylaxis. The University of Chicago Press, Chicago

    Google Scholar 

  11. Rees JK, Coles GA (1969) Calciphylaxis in man. Br Med J 2(5658):670–672

    Article  PubMed  CAS  Google Scholar 

  12. Gipstein RM, Coburn JW, Adams DA, Lee DB, Parsa KP, Sellers A, Suki WN, Massry SG (1976) Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch Intern Med 136(11):1273–1280

    Article  PubMed  CAS  Google Scholar 

  13. Coates T, Kirkland GS, Dymock RB, Murphy BF, Brealey JK, Mathew TH, Disney AP (1998) Cutaneous necrosis from calcific uremic arteriolopathy. Am J Kidney Dis 32(3):384–391

    Article  PubMed  CAS  Google Scholar 

  14. Wilmer WA, Magro CM (2002) Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial 15(3):172–186

    Article  PubMed  Google Scholar 

  15. Hayden MR, Tyagi SC, Kolb L, Sowers JR, Khanna R (2005) 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(1):4

    Article  PubMed  CAS  Google Scholar 

  16. Don BR, Chin AI (2003) A strategy for the treatment of calcific uremic arteriolopathy (calciphylaxis) employing a combination of therapies. Clin Nephrol 59(6):463–470

    PubMed  CAS  Google Scholar 

  17. Yatzidis H (1985) Successful sodium thiosulphate treatment for recurrent calcium urolithiasis. Clin Nephrol 23(2):63–67

    PubMed  CAS  Google Scholar 

  18. Yatzidis H, Agroyannis B (1987) Sodium thiosulfate treatment of soft-tissue calcifications in patients with end-stage renal disease. Perit Dial Int 7(4):250–252

    Google Scholar 

  19. Cicone JS, Petronis JB, Embert CD, Spector DA (2004) Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am J Kidney Dis 43(6):1104–1108

    Article  PubMed  Google Scholar 

  20. Guerra G, Shah RC, Ross EA (2005) Rapid resolution of calciphylaxis with intravenous sodium thiosulphate and continuous venovenous haemofiltration using low calcium replacement fluid: case report. Nephrol Dial Transplant 20:1260–1262

    Article  PubMed  Google Scholar 

  21. Brucculeri M, Cheigh J, Bauer G, Serur D (2005) Long-term intravenous sodium thiosulphate in the treatment of a patient with calciphylaxis. Semin Dial 18:431–434

    Article  PubMed  Google Scholar 

  22. Araya CE, Fennell RS, Neiberger RE, Dharnidharka VR (2006) Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults. Clin J Am Soc Nephrol 1(6):1161–1166

    Article  PubMed  CAS  Google Scholar 

  23. Hayden MR, Kolb LG, Khanna R (2006) Calciphylaxis and the cardiometabolic syndrome. J Cardiometab Syndr 1(1):76–79

    Article  PubMed  Google Scholar 

  24. Meissner M, Bauer R, Beier C, Betz C, Wolter M, Kaufmann R, Gille J (2006) Sodium thiosulphate as a promising therapeutic option to treat calciphylaxis. Dermatology 212:373–376

    Article  PubMed  CAS  Google Scholar 

  25. Tokashiki K, Ishida A, Kouchi M et al (2006) Successful management of critical limb ischemia with intravenous sodium thiosulphate in a chronic hemodialysis patient. Clin Nephrol 66:140–143

    PubMed  CAS  Google Scholar 

  26. Mataic D, Bastani B (2006) Intraperitoneal sodium thiosulphate for the treatment of calciphylaxis. Ren Fail 28:361–363

    Article  PubMed  Google Scholar 

  27. Baker BL, Fitzgibbons CA, Buescher LS (2007) Calciphylaxis responding to sodium thiosulfate therapy. Arch Dermatol 143(2):269–270

    Article  PubMed  Google Scholar 

  28. Ackermann F, Levy A, Daugas E, Schartz N, Riaux A, Derancourt C, Urena P, Lebbé C (2007) Sodium thiosulfate as first-line treatment for calciphylaxis. Arch Dermatol 143(10):1336–1337

    Article  Google Scholar 

  29. Subramaniam K, Wallace H, Sinniah R, Saker B (2008) Complete resolution of recurrent calciphylaxis with long-term intravenous sodium thiosulfate. Australas J Dermatol 49(1):30–34

    Article  PubMed  Google Scholar 

  30. Distrutti E, Sediari L, Mencarelli A et al (2005) Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther 316:325–335

    Article  PubMed  CAS  Google Scholar 

  31. Zanardo RC, Brancaleone V, Distrutti E, Fiorucci S, Cirino G, Wallace JL (2006) Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J 20(12):2118–2120

    Article  PubMed  CAS  Google Scholar 

  32. Yerram P, Saab G, Karuparthi PR, Hayden MR, Khanna R (2007) Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure-role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. Clin J Am Soc Nephrol 2(2):258–263

    Article  PubMed  CAS  Google Scholar 

  33. Al-Khoury S, Afzali B, Shah N, Thomas S, Gusbeth-Tatomir P, Goldsmith D, Covic A (2007) Diabetes, kidney disease and anaemia: time to tackle a troublesome triad? Int J Clin Pract 61(2):281–289

    Article  PubMed  CAS  Google Scholar 

  34. Covic A, Gusbeth-Tatomir P, Goldsmith DJ (2007) Vascular calcification—a new window on the cardiovascular system: role of agents used to manipulate skeletal integrity. Semin Dial 20(2):158–169

    Article  PubMed  Google Scholar 

  35. Rogers NM, Teubner DJ, Coates PT (2007) Calcific uremic arteriolopathy: advances in pathogenesis and treatment. Semin Dial 20(2):150–157

    Article  PubMed  Google Scholar 

  36. Phanish MK, Kallarackal G, Ravanan R et al (2000) Tumoral calcinosis associated with pyrexia and systemic inflammatory response in a haemodialysis patient: successful treatment using intravenous pamidronate. Nephrol Dial Transplant 15:1691–1693

    Article  PubMed  CAS  Google Scholar 

  37. Monney P, Nguyen QV, Perroud H, Descombes E (2004) Rapid improvement of calciphylaxis after intravenous pamidronate therapy in a patient with chronic renal failure. Nephrol Dial Transplant 19(8):2130–2132

    Article  PubMed  Google Scholar 

  38. Musso CG, Enz PA, Guelman R, Mombelli C, Imperiali N, Plantalech L, Kowalczuk A, Galimberti R, Algranati LS (2006) Non-ulcerating calcific uremic arteriolopathy skin lesion treated successfully with intravenous ibandronate. Perit Dial Int 26(6):717–718

    PubMed  CAS  Google Scholar 

  39. Cecchini MG, Felix R, Fleisch H, Cooper PH (1987) Effects of bisphosphonates on proliferation and viability of mouse bone marrow derived macrophages. J Bone Miner Res 2:135–142

    Article  PubMed  CAS  Google Scholar 

  40. Pennanen N, Lapinjoki S, Urtti A, Monkkonen J (1995) Effect of liposomal and free bisphosphonates on IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro. Pharm Res 12:916–922

    Article  PubMed  CAS  Google Scholar 

  41. Sewell LD, Weenig RH, Davis MDP, McEvoy MT, Pittelkow MR (2004) Low dose tissue plasminogen activator for calciphylaxis. Arch Dermatol 140:1043–1048

    Article  Google Scholar 

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Correspondence to Melvin R. Hayden.

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Hayden, M.R., Goldsmith, D., Sowers, J.R. et al. Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate. Int Urol Nephrol 40, 443–451 (2008). https://doi.org/10.1007/s11255-008-9373-4

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  • DOI: https://doi.org/10.1007/s11255-008-9373-4

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