What is Calciphylaxis?

Therapeutic Options

Therapeutic approaches are limited in calciphylaxis. Once calciphylaxis is suspected or diagnosed, the first therapeutic aim must be normalization of the calcium x phosphate product by intensifying dialysis treatment, by using a low dialysate calcium and by high-dose treatment with (preferably calcium-free) phosphate binders.

Reduction or withdrawal of active vitamin D treatment must be considered depending on the corresponding levels of PTH and calcium x phosphorous product. In calciphylaxis patients with hyperparathyroidism and signs of high bone turnover, ‘emergency parathyroidectomy’ should be considered immediately. However, in such patients administration of calcimimetics may represent an effective therapeutic alternative – promising case reports on this conservative intervention have been published recently. Once progressive ulcerations and necrosis are observed, early broad-spectrum antibiotics should probably be initiated.

Some data are available concerning the use of sodium thiosulfate and of bisphosphonates in the treatment of calciphylaxis. Thiosulfate is available as a chelating agent indicated for the treatment of cyanide intoxication. On the one hand, it possesses a high affinity to calcium ions, which may interfere with calcium and phosphate precipitation producing soluble calcium thiosulfate which can potentially be removed by dialysis. On the other hand, thiosulfate may also interfere with the local inflammation process by antioxidant properties. Both concepts currently lack proof.

It is currently unclear whether bisphosphonates interact with extraosseous calcification processes via their antiresorptive bone effects or via direct peripheral pyrophosphate-like effects at the tissue sites. Although case reports on beneficial effects of pamidronate in calciphylaxis patients have recently been published, caution is advised concerning uncritical use of bisphosphonates unless ABD is excluded or highly unlikely, since ABD will be aggravated by these compounds, especially in renal failure patients.

In patients on warfarin treatment, warfarin withdrawal and switch to heparin use is urgently recommended, despite a lack of clear-cut prospective clinical evidence. However, the biological plausibility that vitamin K antagonism favours vascular calcification is relevant and vitamin K supplementation may be valuable. Basile et al. reported on successful hyperbaric oxygen therapy in a small number of calciphylaxis patients. This approach is based on the attempt to improve wound healing in ischemic tissues. In this study, affected areas were exposed to 100% oxygen at 2.5-atmospheres pressure in a closed chamber for 90 minutes per session in order to increase local oxygen pressure in the ulcerated and necrotic areas (number of session per patient ranged between 20 and 108). 8 out of 11 patients showed effective healing of ulcerations.

Finally, Fine and Zacharias reported on 36 calciphylaxis patients at different stages of the disease and on successful glucocorticoid treatment in early, non-ulcerated stages. However, with regard to the threat of superinfection, glucocorticoids should certainly be avoided in patients with advanced lesions because of their immunosuppressive properties.

Calciphylaxis Registries

Current data on incidence, pathophysiology, diagnosis and therapeutic strategies for calciphylaxis is limited. This situation was considered by the ‘Kidney Disease – Improving Global Outcomes’ (KDIGO) initiative, a global and independent non-profit organization, aiming at improvements of the general prognosis of all CKD-associated outcomes. KDIGO developed the concept of prospectively collecting as many calciphylaxis cases as possible to improve understanding of the epidemiology of this syndrome and to collect samples (serum, DNA, biopsy tissues etc.) for evaluation of novel pathological mechanisms and risk factors and for setting up data and tissue banking.

For these purposes, calciphylaxis registries have been founded in Germany (Aachen/Coburg) and now Australia, representing the initial stage of an ‘International Collaborative Calciphylaxis Network (ICCN)’. Once such registries are more widely established, they may represent the basis for future prospective treatment trials.