Pathophysiology & risk factors
Pathophysiology
- Medial calcification of dermal/subcutaneous arterioles
- Intimal proliferation + thrombosis → tissue ischaemia + panniculitis + necrosis
- Imbalance between calcification promoters (high PO4, high Ca, high PTH) and inhibitors (matrix Gla protein — requires vitamin K)
- Warfarin inhibits vitamin K → inactive matrix Gla protein → unrestrained calcification
Risk Factors
- Haemodialysis vintage > 2 years
- Female sex, obesity, diabetes
- Warfarin use (strongest modifiable drug risk)
- Hyperphosphataemia, raised Ca×PO4 product
- Hypercalcaemia, calcium-based binders, active vitamin D excess
- Raised PTH (or oversuppressed PTH < 150 — adynamic bone)
- Hypoalbuminaemia, malnutrition
- Recent trauma, SC injection sites (insulin, heparin, LMWH)
- Non-uraemic calciphylaxis: primary hyperparathyroidism, hypercoagulable states, malignancy, autoimmune disease
Diagnosis
Clinical Features
- Extremely painful skin lesions, often out of proportion to appearance
- Early: livedo racemosa, retiform (net-like) purpura, indurated subcutaneous nodules
- Late: well-demarcated black eschars, ulcers with violaceous borders, slow healing
- Distribution: adipose-rich sites — abdomen, thighs, buttocks, breasts (proximal disease)
- Distal disease: fingers, toes, penis — better prognosis
- Secondary infection common — wound swabs and blood cultures if febrile
Investigations
- Bloods: Ca, PO4, PTH, ALP, 25-OH vitamin D, albumin, CRP, FBC, U&E
- Imaging: plain radiographs may show vascular calcification
- Bone scintigraphy: increased uptake at affected sites (sensitive, non-specific)
- Skin biopsy from edge of lesion: small-vessel medial calcification, intimal hyperplasia, microthrombi, panniculitis — gold standard, but risks worsening ulceration; consider only if diagnosis uncertain
Differential
- Warfarin skin necrosis (acute, often breast/thigh in first 2 weeks)
- Cholesterol embolism
- Vasculitis (ANCA, cryoglobulinaemic)
- Necrotising fasciitis
- Pyoderma gangrenosum
- Embolic / thrombotic vasculopathy
Management
Multidisciplinary Team
- Nephrology + dermatology + tissue viability + pain team + palliative care + dietitian + microbiology
Metabolic Control
- STOP WARFARIN — switch to DOAC (apixaban) if anticoagulation needed
- Stop calcium-containing binders → switch to non-calcium binders (sevelamer, lanthanum)
- Stop active vitamin D analogues if Ca or PTH elevated
- Aim phosphate < 1.5 mmol/L, corrected Ca 2.10–2.37 mmol/L, PTH 150–600 pg/mL
- Cinacalcet for raised PTH
- Parathyroidectomy for refractory secondary HPT with calciphylaxis
Dialysis Intensification
- Increase HD to 4–5 sessions/week or extend to 4–5 h
- Low-calcium dialysate (1.25 mmol/L)
- Convert PD to HD if poor response
Iv Sodium Thiosulfate
- 25 g in 100 mL saline over the last 30–60 min of each HD session, 3× weekly
- Chelates calcium and provides antioxidant effect
- Side effects: nausea, hypotension, anion-gap metabolic acidosis — adjust dialysate bicarbonate
- Typical duration 3–6 months; continue until ulcers healed
Wound Care
- Daily review; avoid debridement of dry eschars unless infected (poor granulation)
- Non-adherent dressings; hyperbaric oxygen in selected cases
- Pain: opioids (avoid morphine in CKD; use oxycodone or fentanyl); ketamine and gabapentinoids for neuropathic pain
- Infection: low threshold for broad-spectrum antibiotics; cover MRSA in proven cases
- Avoid further SC injections in affected areas
Vitamin K
- Some centres use vitamin K replacement (MK-7) for vitamin K deficiency, though evidence limited
Palliative / Supportive Care
- Early advance care planning given high mortality
- Recognise withdrawal of dialysis is a legitimate option when quality of life is poor
- Hospice / community palliative team input
Prevention
- Avoid warfarin in dialysis patients with AF unless absolute need
- Maintain phosphate control with non-calcium binders
- Avoid calcium loading from binders
- Treat secondary HPT proactively
- Adequate vitamin K intake
