Calciphylaxis as a multidisciplinary problem: important information (not only) for clinical osteologists and case reports

Authors: Sulková Dusilová Sylvie 1,2;  Šafránek Roman 1,2;  Pokorná Anita 1;  Soukup Tomáš 3;  Bělobrádková Martina 3;  Horáček Jiří 6;  Bláha Vladimír 4;  Palička Vladimír 5
Authors‘ workplace: Hemodialyzační středisko FN Hradec Králové 1;  Katedra interních oborů LF UK, Hradec Králové 2;  II. interní gastroenterologická klinika LF UK a FN Hradec Králové 3;  III. gerontometabolická klinika LF UK a FN Hradec Králové 4;  Osteocentrum, Ústav klinické biochemie a diagnostiky LF UK a FN Hradec Králové 5;  IV. interní hematologická klinika LF UK a FN Hradec Králové 6
Published in: Clinical Osteology 2019; 24(4): 205-215


Calciphylaxis (CUA – calcifying uremic arteriolopathy) is a serious clinical complications characterized by large and painful skin and subcutaneous tissue ulcerations and necrosis, associated with the risk of sepsis and mortality. Its pathogenesis is quite complicated. Despite it is a rare entity, physicians of all specialities may meet this disease. Therefore, this paper focuses on principal characteristics of CUA, risk factors in pathogenesis (namely calcium and phosphate metabolism disturbances, hyperparathyroidism, and association with warfarin therapy), as well as on therapeutics principles and possibilities. The most promising current therapy approach is administration of sodium thiosulfate. Three case reports are presented for illustration.


warfarin – calcifying uremic arteriolopathy – calciphylaxis – hyperparathyroidism – matrix GLA mortality protein – sepsis – skin necrosis – sodium thiosulfate – surgical parathyroidectomy

  1. Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med 2018; 378(18): 1704–1714. Dostupné z DOI: <>.
  2. Nigwekar SU, Kroshinsky D, Nazarioan RM et al. Calciphylaxis: Risk factors, diagnosis and treatment. Am J Kidney Dis 2015; 66(1): 133–146. Dostupné z DOI: <>.
  3. Nigwekar SU, Wolf M, Sterns RH et al: Calciphylaxis for nonuremic causes. A systematic review. Clin J Am Soc Nephrol 2008; 3(4): 1139–1143. Dostupné z DOI: <>.
  4. Jouhhadar R, Bright T. Calciphylaxis in primary hyperparathyroidism: a case report a brief review. South Med J 2009; 102(3): 318–21. Dostupné z DOI: <>.
  5. Kusari A, Cotter D, Hinds B et al. Non-uremic calciphylaxis in a patient with multiple rheumatologic diseases. Dermatol Online J 2019; 25(2). Dostupné z PII: <https://pii: 13030/qt2fg525bs>.
  6. Dobry AS, Ko LN, St John J et al. Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease: A Case-Control Study. JAMA Dermatol 2018; 154 (2): 182–187. Dostupné z DOI: <>.
  7. Monegal A, Peris P, Alsina M et al. Development of multiorganic calciphylaxis during teriparatide, vitamin D, and calcium treatment. Osteoporos Int 2016; 27(8): 2631–2634. Dostupné z DOI: <–016–3571–1>.
  8. Storan ER, O’Gorman SM, Murphy A et al. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D3 Supplementation. J Cutan Med Surg 2017; 21(2): 162–163. Dostupné z DOI: <>.
  9. Spanakis EK, Sellmeyer DE. Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1–34)] therapy in the setting of chronic warfarin and glucocorticoid treatment. Osteoporos Int 2014; 25(4): 1411–1414. Dostupné z DOI: <–013–2580–6>.
  10. Shah DS, Williamson DJ. A rare cause of ulceration with a promising new treatment. Calciphylaxis due to secondary hyperparathyroidism caused by vitamin D deficiency. Clin Exp Dermatol 2010; 35(3): e90–93. Dostupné z DOI: <–2230.2009.03558.x>.
  11. Mawad HW, Sawaya BP, Sarin R et al. Calcific uremic arteriolopathy in association with low turnover uremic bone disease. Clin Nephrol. 1999; 52(3): 160–166
  12. Nasr R, Ghazanfar H. Parathyroidectomy as a Cure for Calciphylaxis in a Non-Dialysis Chronic Kidney Disease Patient? Am J Case Rep 2019; 20: 1170–1174. Dostupné z DOI: <>.
  13. Karmegam S, Shetty A. Calciphylaxis after parathyreoidectomy. Hemodial Int 2017; 21(Suppl 2): 2S62–2S66. Dostupné z DOI: <>.
  14. Erdel BL, Juneja R, Evans-Molina C. A case of calciphylaxis in a patient with hypoparathyroidism and normal renal function. Endocr Pract 2014; 20(6): e102–e105. Dostupné z DOI: <>.
  15. Brandenburg VM, Evenepoel P, Floege J et al. [ERA-EDTA working group on CKD-MBD and EUCALNET]. Lack of evidence does not justify neglect: how can we address unmet medical needs in calciphylaxis? Nephrol Dial Transplant 2016; 31(8): 1211–1219. Dostupné z DOI: <>.
  16. Nigwekar SH, Zhao S, Wenger J et al. A nationally representative study of calcific uremic arteriolopathy risk factors. J Am Soc Nephrol 2016; 27(11): 3421–3429. Dostupné z DOI: <>.
  17. Dusilová Sulková S, Horáček J, Vykoukalová E et al. Parathyreoidectomy in hyperparathyroidism-associated calciphylaxis in end-stage renal disease should be prompt and radical – a case report with two original therapeutic modifications and successful outcome. Acta Medica (Hradec Králové) 2017; 60(2): 85–88. Dostupné z DOI: <>.
  18. Nigwekar SU. Multidisciplinary approach to calcific uremic arteriolopathy. Curr Opin Nephrol Hypertens 2015; 24(6): 531–7. Dostupné z DOI: <>.
  19. McCarthy JT, El-Azhary RA, Patzelt MT et al. Survival, risk factors, and effect of treatment in 101 patients with calciphylaxis. Mayo Clin Proc 2016 91(10): 1384–1394. Dostupné z DOI: <>.
  20. Peng T, Zhuo L, Wang Y et al. Systematic review of sodium thiosulfate in treating calciphylaxis in chronic kidney disease patients. Nephrology (Carlton) 2018; 23(7): 669–675. Dostupné z DOI: <>.
  21. Brandenburg VM, Kramann R, Rothe H et al. Calcific uremic arteriolopathy (calciphylaxis): data from a large nationwide registry. Nephrol Dial Transplant 2017; 32(1): 126–132. Dostupné z DOI: <>.
  22. Asobie N, Wong E, Cook M. Calciphylaxis in a Diabetic Patient Provoked by Warfarin Therapy. Clin Exp Dermatol 2008; 33(3): 342–344. Dostupné z DOI: <–2230.2007.02626.x>.
  23. Al-Ani M, Parperis K. Warfarin-induced calciphylaxis. BMJ Case Rep 2016. Dostupné z DOI: <–214142>.
  24. Yu WY, Bhutani T, Kornik R et al. Warfarin-Associated Nonuremic Calciphylaxis. JAMA Dermatol 2017; 153(3): 309–314. Dostupné z DOI: <>.
  25. Ketteler M, Brandenburg VM. K-alcification protection in dialysis patients: the underestimated phenomenon of vitamin K deficiency. J Am Soc Nephrol 2017; 28(6): 1667–1668. Dostupné z DOI: <>.
  26. Yu WY, Bhutani T, Kornik L et al. Warfarin-Associated Nonuremic Calciphylaxis. JAMA Dermatol 2017; 153(3): 309–314. Dostupné z DOI: <>.
  27. Nigwekar SU, Bloch BD, Nazarian RM et al. Vitamin K–Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. J Am Soc Nephrol 2017; 28(6): 1717–1722. Dostupné z DOI: <>.
  28. Hasegava H. Clinical Assessment of Warfarin Therapy in Patients with Maintenance Dialysis-Clinical Efficacy, Risks and Development of Calciphylaxis. Ann Vasc Dis. 2017; 10(3): 170–177. Dostupné z DOI: <–00062>.
  29. Chen TY, Lehman LJ, Gibson JE et al. Histopathology of Calciphylaxis: Cohort Study With Clinical Correlations. Am J Dermatopathol 2017; 39(11): 795–802. Dostupné z DOI: <>.
  30. Kazanji N, Falatko J, Neupane S et al. Calciphylaxis presenting as digital ischemia. Intern Emerg Med 2015; 10(4): 529–30. Dostupné z DOI: <–014–1172–6>.
  31. Gupta N, Haq KF, Mahajan S et al. Gastrointestinal Bleeding Secondary to Calciphylaxis. Am J Case Rep 2015; 16:818–822. Dostupné z DOI: <>.
  32. Colboc H, Moguelet P, Bazin D et al. Localization, Morphologic Features, and Chemical Composition of Calciphylaxis-Related Skin Deposits in Patients With Calcific Uremic Arteriolopathy. JAMA Dermatology 2019; 155(7): 789–796. Dostupné z DOI: <>.
  33. Williams EA, Moy AP, Cipriani NA et al. Factors associated with false-negative pathologic diagnosis of calciphylaxis. J Cutan Pathol 2019; 46(1): 16–25. Dostupné z DOI: <>.
  34. Ellis CL, O’Neill WC. Questionable specificity of histologic findings in calcific uremic arteriolopathy. Kidney Int 2018; 94(2):390–395. Dostupné z DOI: <>.
  35. Schäfer C, Heiss A, Schwarz A et al. The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112(3): 357–366. Dostupné z DOI: <>.
  36. Schlieper G, Brandenburg V, Ketteler M et al. Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol 2009; 5(9): 539–543. Dostupné z DOI: <>.
  37. Carrell EJ, Bell A. Sodium thiosulfate for the treatment of warfarin-induced calciphylaxis in a nondialysis patients. J Pharmacol Pharmacother 2015; 6(4): 222–224. Dostupné z DOI: <–500X.171882>.
  38. Schlieper G1, Brandenburg V, Ketteler M et al. Sodium thiosulfate in the treatment of calcific uremic arteriolopathy. Nat Rev Nephrol; 5(9): 539–543. Dostupné z DOI: <>.
  39. Strazzula L, Nigwekar SU, Steele D et al. Intralesional sodium thiosulfate for the treatment of calciphylaxis. JAMA Dermatol 2013; 149(8): 946–949. Dostupné z DOI: <>.
  40. Mao M, Lee S, Kashani K et al: Severe anion gap acidosis associated with intravenous sodium thiosulfate administration. J Med Toxicol 2013; 9(3): 274–247. Dostupné z DOI: <–013–0305-z>.
  41. Russ P, Russwurm M, Kortus-Goetze B et al. Phenprocoumon based anticoagulation is an underestimated factor in the pathogenesis of calciphylaxis. BMC Nephrol 2019; 20(1): 114. Dostupné z DOI: <–019–1301–6>.
  42. Hansjoerg Rothe H, Brandenburg V, Haun et al. Ecto-5’ -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients. Data from the German Calciphylaxis Registry. PLoS ONE 2017; 12(2): e0172407. Dostupné z DOI: <>.
  43. El-Azhary RA, Patzelt MT, McBane RD et al: Calciphylaxis: A disease of pannicular trombosis. Mayo Clinic Proc 2016; 91(10): 1395–1402. Dostupné z DOI: <>.
  44. Randall DP, Fisher MA, Thomas C. Rhabdomyolysis as the presenting manifestation of calciphylaxis. Muscle Nerve 2000; 23(2):289–293. Dostupné z DOI: <–4598(200002)23:2<289::aid-mus24>; 2-h>.
  45. Bishop J, Brown E, Podesta A et al. Surgical Management of Calciphylaxis Associated with Primary Hyperparathyroidism: A Case Report and Review of the Literature Int J Endocrinol. Int J Endocrinol 2010; 2010. Dostupné z DOI: <>.
  46. Roy R, Lee JA. Calciphylaxis due to hyperparathyroidism. Endocr Pract 2011; 17(Suppl 1): 54–56. Dostupné z DOI: <>.
  47. Thompson B, Towler DA. Arterial calcification and bone physiology: role of the bone vascular axis. Nat Rev Endocrinol 2012; 8(9): 529–543. Dostupné z DOI: <>.
  48. Garza-Mayers AC, Shah R, Sykes DB et al. The Successful Use of Apixaban in Dialysis Patients with Calciphylaxis Who Require Anticoagulation: A Retrospective Analysis. Am J Nephrol. 2018; 48(3):168–171. Dostupné z DOI: <>.
  49. Disthabanchong S, Srisuwarn P. Mechanism of vascular calcification in kidney disease. Adv Chron Kidney Dis 2019, 26(6): 417–426. Dostupné z DOI: <>.
  50. Voelkl J, Lang F, Eckardt KU et al. Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia. Cell Mol Life Sci 2019; 76(11): 2077–2091. Dostupné z DOI: <–019–03054-z>.
Clinical biochemistry Paediatric gynaecology Paediatric radiology Paediatric rheumatology Endocrinology Gynaecology and obstetrics Internal medicine Orthopaedics General practitioner for adults Radiodiagnostics Rehabilitation Rheumatology Traumatology
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