What is the management approach for calciphylaxis?

Management of Calciphylaxis

Immediately initiate sodium thiosulfate (12.5-25g per dialysis session, 2-3 times weekly for 3-6 months) and discontinue all vitamin K antagonists as first-line therapy. 1

Immediate Medication Adjustments

• Stop warfarin and all vitamin K antagonists immediately – these medications increase calciphylaxis risk up to 11-fold, particularly in end-stage renal disease patients 1, 2
• Discontinue calcium-containing phosphate binders, active vitamin D derivatives, calcium supplements, and iron preparations 1, 3
• If anticoagulation is required for atrial fibrillation, consider reduced-dose apixaban as a safer alternative to warfarin in dialysis patients 1

First-Line Pharmacologic Therapy

• Sodium thiosulfate is the primary treatment: administer 12.5-25g per hemodialysis session, 2-3 times weekly, continuing for 3-6 months 1, 2
• Consider magnesium supplementation (magnesium oxide or hydroxide) to prevent phosphate-induced vascular calcification, though evidence remains mixed 1, 2
• SNF472 (hexaphosphate phytate) shows promise in clinical trials with improved wound healing and reduced hospitalizations, representing an emerging therapeutic option 4, 2

Surgical Intervention Criteria

• Perform parathyroidectomy when PTH levels exceed 500 pg/mL (55.0 pmol/L) in patients with calciphylaxis and elevated parathyroid hormone 1, 2
• Earlier parathyroidectomy correlates with better outcomes – mean time from symptom onset to surgery should be minimized (historical data shows 8 weeks average, but earlier is better) 5
• Lesion severity at time of parathyroidectomy best predicts clinical course and mortality 5

Essential Supportive Care

• Aggressive pain control is mandatory – calciphylaxis lesions are extremely painful and require prioritization of analgesic therapy 1
• Implement meticulous wound care with aggressive debridement of necrotic tissue 6
• Avoid traumatizing vulnerable tissue during wound care or diagnostic procedures 4, 2

Diagnostic Approach

• C-reactive protein is the most useful laboratory test for diagnosis and monitoring inflammatory response to treatment 1, 4, 2
• Do not rely on serum calcium and phosphate levels for diagnosis or treatment guidance – these are not predictive of outcomes 4, 2
• Avoid routine skin biopsy due to variable sensitivity (20-80%), lack of validated histologic criteria, and risk of creating additional non-healing ulcers in vulnerable tissue 1, 4, 2

Monitoring Strategy

• Assess wound healing progression regularly 2
• Monitor C-reactive protein levels to track inflammatory response 4, 2
• Perform ongoing vascular surveillance for calcification progression 2

Critical Pitfalls to Avoid

• Do not aggressively lower phosphate in patients without overt hyperphosphatemia – this has safety concerns and limited evidence of benefit 2
• Recognize that calciphylaxis can occur even with normal calcium and phosphate levels 2
• Understand that mortality remains high (up to 80% at one year with ulcerations), primarily from sepsis due to infected ulcers 1, 7
• Initiate advanced care planning and shared decision-making early given the poor prognosis 1

Treatment Algorithm Priority

1. Immediate: Stop warfarin, calcium supplements, active vitamin D, and iron
2. Within 24-48 hours: Start sodium thiosulfate with dialysis sessions
3. Within 1 week: Check PTH levels and C-reactive protein
4. If PTH >500 pg/mL: Arrange urgent parathyroidectomy consultation
5. Ongoing: Aggressive wound care, pain management, and infection surveillance

The evidence for calciphylaxis management remains limited due to its rarity, but the National Kidney Foundation and recent consensus guidelines provide clear direction for first-line interventions 1, 8. The multidisciplinary approach combining sodium thiosulfate, medication discontinuation, and surgical intervention for elevated PTH represents the current standard of care 1, 2, 6.