Clinical and Experimental Nephrology

, Volume 17, Issue 4, pp 498–503 | Cite as

Calciphylaxis: diagnosis and clinical features

  • Matsuhiko HayashiEmail author
Review Article


Calciphylaxis is a relatively rare disease, observed mainly in patients on dialysis, associated with high mortality rates, and characterized by painful skin ulceration. The pathogenesis of calciphylaxis is virtually unknown, although several risk factors, including warfarin therapy, hypoalbuminemia, and disturbances in calcium–phosphate metabolism, have been reported. The prevalence of calciphylaxis in Japan is likely to be less than 1:10,000 dialysis patients per year based on our nationwide survey in 2009. However, the results of the survey also showed that about 60 % of nephrologists in Japan are not familiar with the disease itself and it is highly likely that calciphylaxis is being overlooked. To facilitate recognition of calciphylaxis, we have proposed diagnostic criteria. At present, there is no specific therapy for calciphylaxis and general supportive measures, especially antibiotics for the accompanying infection and wound care, are important. Recently, sodium thiosulfate has been increasingly used to treat calciphylaxis and its efficacy should be evaluated by large clinical trials.


Calciphylaxis Hemodialysis Warfarin Sodium thiosulfate 



I would like to thank M. Iwai for secretarial assistance and collection of clinical data.

Conflict of interest

MH has received research grants and lecture fees from Kyowa Hakko Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., and MSD Co. Ltd.


  1. 1.
    Weenig RH. Pathogenesis of calciphylaxis. Hans Selye to nuclear factor κ-B. J Am Acad Dermatol. 2008;58:458–71.PubMedCrossRefGoogle Scholar
  2. 2.
    Rogers NM, Coates PT. Calcific uraemic arteriolopathy: an update. Curr Opin Nephrol Hypertens. 2008;17:629–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Selye H, Gentile G, Prioreschi P. Cutaneous molt induced by calciphylaxis in the rat. Science. 1961;134:1876–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson DC, Stewart WK, Piercy DM. Calcifying panniculitis with fat and skin necrosis in a case of uraemia with autonomous hyperparathyroidism. Lancet. 1968;2(7563):323–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Rees JK, Coles GA. Calciphylaxis in man. Br Med J. 1969;2(5658):670–2.PubMedCrossRefGoogle Scholar
  6. 6.
    Richardson JA, Herron G, Reitz R, Layzer R. Ischemic ulcerations of skin and necrosis of muscle in azotemic hyperparathyroidism. Ann Intern Med. 1969;71:129–38.PubMedCrossRefGoogle Scholar
  7. 7.
    Gipstein RM, Coburn JW, Adams DA, Lee DB, Parsa KP, Sellers A, Suki WN, Massry SG. Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch Intern Med. 1976;136:1273–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Hayashi M,Takamatsu I, Kanno Y, Yoshida T, Abe T, Sato Y, the Japanese Calciphylaxis Study Group. A case-control study of calciphylaxis in Japanese end-stage renal disease patients. Nephrol Dial Transpl. 2012;27:1580–84.Google Scholar
  9. 9.
    Hayashi M, Takamatsu I, Yoshida T, Kanno Y, Sato Y, Abe T, Hashimoto A, Hosoya T, Akiba T, Nakamoto H, Umezawa A, Shigematsu T, Fukagawa M, Kawamura T, Tanaka M, Sugino Y, The Japanese Calciphylaxis Group. Proposal of diagnostic criteria for calciphylaxis based on nationwide surveillance in Japan. J Jpn Soc Dial Ther. 2012;45:551–7 (English abstract).Google Scholar
  10. 10.
    Daudén E, Oñate MJ. Calciphylaxis. Dermatol Clin. 2008;26:557–68.PubMedCrossRefGoogle Scholar
  11. 11.
    Ng AT, Peng DH. Calciphylaxis. Dermatol Ther. 2011;24:256–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Karpman E, Das S, Kurzrock EA. Penile calciphylaxis: analysis of risk factors and mortality. J. Urol. 2003;169(6):2206–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Bleyer AJ, Choi M, Igwemezie B, de la Torre E, White WL. A case control study of proximal calciphylaxis. Am J Kidney Dis. 1998;32:376–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL, Stehman-Breen CO. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001;60:324–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. Kidney Int. 2002;61:2210–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR. Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol. 2007;56:569–79.PubMedCrossRefGoogle Scholar
  17. 17.
    Girotto JA, Harmon JW, Ratner LE, Nicol TL, Wong L, Chen H. Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism. Surgery. 2001;130:645–50.PubMedCrossRefGoogle Scholar
  18. 18.
    Janigan DT, Hirsch DJ, Klassen GA, MacDonald AS. Calcified subcutaneous arterioles with infarcts of the subcutis and skin (“calciphylaxis”) in chronic renal failure. Am J Kidney Dis. 2000;35:588–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM. Warfarin-induced skin necrosis. J Am Acad Dermatol. 2009;61(2):325–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Lal G, Nowell AG, Liao J, Sugg SL, Weigel RJ, Howe JR. Determinants of survival in patients with calciphylaxis: a multivariate analysis. Surgery. 2009;146:1028–34.PubMedCrossRefGoogle Scholar
  21. 21.
    Vedvyas C, Winterfield LS, Vleugels RA. Calciphylaxis: a systematic review of existing and emerging therapies. J Am Acad Dermatol. 2012;67:e253–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial. 2002;15:172–86.PubMedCrossRefGoogle Scholar
  23. 23.
    Cicone JS, Petronis JB, Embert CD, Spector DA. Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am J Kidney Dis. 2004;43:1104–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Schlieper G, Brandenburg V, Ketteler M, Floege J. Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol. 2009;5:539–43.PubMedCrossRefGoogle Scholar
  25. 25.
    Sood AR, Wazny LD, Raymond CB, Leung K, Komenda P, Reslerova M, Verrelli M, Rigatto C, Sood MM. Sodium thiosulfate-based treatment in calcific uremic arteriolopathy: a consecutive case series. Clin Nephrol. 2011;75:8–15.PubMedGoogle Scholar
  26. 26.
    Noureddine L, Landis M, Patel N, Moe SM. Efficacy of sodium thiosulfate for the treatment for calciphylaxis. Clin Nephrol. 2011;75:485–90.PubMedGoogle Scholar
  27. 27.
    Kyriakopoulos G, Kontogianni K. Sodium thiosulfate treatment of tumoral calcinosis in patients with end-stage renal disease. Ren Fail. 1990;12:213–9.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2013

Authors and Affiliations

  1. 1.Apheresis and Dialysis Center, School of MedicineKeio UniversityTokyoJapan

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