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 Changes

• Stop warfarin and all vitamin K antagonists immediately – these increase calciphylaxis risk up to 11-fold, particularly in end-stage renal disease patients 1, 2
• Discontinue active vitamin D derivatives, calcium supplements, and iron preparations as these contribute to calcium loading and vascular calcification 3, 1
• Switch anticoagulation to reduced-dose apixaban if anticoagulation is absolutely necessary for conditions like atrial fibrillation 1
• Stop calcium-containing phosphate binders to prevent further calcium loading 1

First-Line Pharmacologic Therapy

• Administer sodium thiosulfate at 12.5-25g per hemodialysis session, 2-3 times weekly, continuing for 3-6 months – this is the National Kidney Foundation's recommended first-line therapy 1, 2
• Consider magnesium supplementation (magnesium oxide or hydroxide) to help prevent phosphate-induced vascular calcification, though evidence remains mixed 1, 2

Surgical Intervention Based on PTH Levels

• Perform parathyroidectomy if PTH levels exceed 500 pg/mL (55.0 pmol/L) – this is indicated for patients with elevated parathyroid hormone driving the calcification process 1, 2
• Earlier parathyroidectomy correlates with better outcomes; lesion severity at time of surgery best predicts clinical course and mortality 4
• Timing matters: the mean 8-week delay between symptom onset and parathyroidectomy in historical series was associated with high mortality from wound-related sepsis 4

Essential Supportive Care

• Prioritize aggressive pain control – calciphylaxis lesions are extremely painful and adequate analgesia is essential for quality of life 1
• Implement meticulous wound care with aggressive debridement of necrotic tissue to prevent sepsis, the leading cause of death 5, 6
• Avoid traumatizing vulnerable tissue during wound care or diagnostic procedures 7, 2

Diagnostic Monitoring

• Measure C-reactive protein as the most helpful laboratory test – it reflects the inflammatory component and helps monitor treatment response 1, 7, 2
• Do not rely on serum calcium and phosphate levels for guiding therapy or predicting outcomes, as these are not predictive in calciphylaxis 7, 2
• Avoid routine skin biopsy – sensitivity is only 20-80%, there are no validated histologic criteria, and biopsy risks triggering additional non-healing ulcers in already vulnerable tissue 1, 7, 2

Critical Pitfalls to Avoid

• Do not aggressively lower phosphate in patients without overt hyperphosphatemia – there are safety concerns and limited evidence of benefit 2
• Recognize that calciphylaxis can occur even with normal calcium and phosphate levels, so normal labs do not exclude the diagnosis 2
• Avoid routine correction of hypocalcemia; treatment should be individualized rather than automatic 2
• Do not delay intervention waiting for biopsy confirmation given the poor sensitivity and risk of tissue trauma 7, 2

Emerging Therapies

• SNF472 (hexaphosphate phytate) shows promise in clinical trials with improvements in wound healing and reduced hospitalizations, though not yet standard therapy 7, 2

Prognosis and Advanced Care Planning

• Mortality remains extremely high (up to 80% at one year with ulcerations), primarily from sepsis secondary to infected wounds 6, 4
• Initiate early discussions about goals of care and advanced care planning given the poor prognosis despite aggressive treatment 1
• Regular monitoring should include wound healing assessment, inflammatory markers, and vascular surveillance for calcification progression 1, 2