What is the treatment for calciphylaxis in patients with end-stage renal disease (ESRD)?

From the Guidelines

Calciphylaxis is a rare and life-threatening complication of chronic kidney disease-mineral and bone disorder (CKD-MBD) characterized by vascular calcification, inflammation, and tissue ischemia in the setting of uremic toxins and mineral metabolism disorders. The treatment for calciphylaxis in patients with end-stage renal disease (ESRD) requires a multifaceted approach focusing on wound care, pain management, and addressing underlying metabolic abnormalities.

Key Aspects of Treatment

• Wound care is essential and involves gentle debridement of necrotic tissue, sterile dressings, and infection prevention with appropriate antibiotics when necessary.
• Pain control with opioid analgesics is often required due to the severe pain associated with calciphylaxis lesions.
• Normalizing calcium-phosphate metabolism is crucial, which may involve discontinuing calcium-based phosphate binders, vitamin D analogs, and using non-calcium phosphate binders like sevelamer.
• Parathyroid hormone levels should be controlled, potentially using cinacalcet (30-180 mg daily) or parathyroidectomy in severe cases.
• Dialysis optimization with increased frequency or duration and low calcium dialysate may help.
• Hyperbaric oxygen therapy (20-40 sessions at 2.0-2.5 atmospheres) can promote wound healing by increasing tissue oxygenation.
• Bisphosphonates like etidronate may be considered to inhibit calcium deposition.
• Nutritional support is important as these patients often have protein-energy wasting.

Emerging Therapies

• SNF472, a hexaphosphate phytate, has shown promise in inhibiting calcification and improving wound healing in calciphylaxis patients, as demonstrated in the CALCIPHYX trial 1.
• Sodium thiosulfate is widely used for treating calciphylaxis, although its effectiveness has not been established in randomized controlled trials 1.

Diagnosis and Management Considerations

• Skin biopsy is not a reliable diagnostic tool for calciphylaxis due to inadequate sampling, variable sensitivity, and the risk of triggering additional nonhealing ulcers 1.
• A multimodal approach to managing calciphylaxis is suggested, including advanced care planning, pain control, shared decision-making, and dialysis treatment options 1. The use of SNF472 may offer a new therapeutic option for calciphylaxis patients, and its potential benefits should be considered in the context of individual patient care.

From the Research

Definition of Calciphylaxis

• Calciphylaxis is a rare and severe medical condition characterized by the calcification of small blood vessels and soft tissues, leading to tissue damage, skin ulcers, and intense pain 2, 3.
• It is classically described in uraemic patients with end-stage renal failure who are on dialysis or had previous renal transplant, but it can also occur in non-uraemic patients and those on warfarin therapy 2.

Treatment of Calciphylaxis in Patients with End-Stage Renal Disease (ESRD)

• The treatment of calciphylaxis is a multidisciplinary approach that involves elimination of risk factors, wound management, pain control, and optimization of calcium/phosphorus metabolism 2, 3.
• The primary goals of treatment are to alleviate pain, promote wound healing, address underlying causes, and prevent further complications 3.
• Treatment strategies may include the use of sodium thiosulfate, bisphosphonates, and cinacalcet to modify calcium and phosphate concentrations and hyperparathyroidism 4.
• Hyperbaric oxygen therapy (HBOT) has also been shown to be effective in healing calciphylaxis lesions in some patients 5.

Management Strategies

• A multifaceted approach is recommended for the management of calciphylaxis, including a collaborative effort between nephrologists, dermatologists, and wound care experts 3, 6.
• Sodium thiosulfate and calcimimetic are commonly used management strategies, but no significant benefit has been shown with any individual treatment modality 6.
• The use of combination therapy with cinacalcet and sodium thiosulfate has been reported, but further research is necessary to fully describe the optimal use of these treatments 4.

Outcomes and Prognosis

• Calciphylaxis is associated with very high mortality rates, particularly in patients with end-stage renal disease 2, 6.
• The mortality rate for patients with calciphylaxis is significantly higher than for those without the condition, with an annual mortality rate of 67% versus 10.2% in haemodialysis patients without calciphylaxis 6.
• Complete wound healing is possible in some patients, but the prognosis is generally poor, with a high risk of complications and mortality 6, 5.