II. Definitions
- Calciphylaxis (Calcific Uremic Arteriolopathy)
- Rare, often lethal complication of Hemodialysis in End Stage Renal Disease
- Characterized by cutaneous arteriolar calcification, thrombosis and skin necrosis
III. Epidemiology
- Incidence in Hemodialysis patients: 0.04 to 4%
- Rare outside of Kidney disease
IV. Pathophysiology
- Nearly exclusive to Hemodialysis patients (may require cessation of Hemodialysis)
- Pathogenesis
- Vascular endothelial injury
- Vascular calcification of the tunica media (middle) layer of arterioles and small arteries
- Microthrombi complicate an already narrowed arteriole lumen resulting in tissue ischemia and infarction
- Skin lesions are pathognomonic, but arteriole calcification is systemic and diffuse end organ effects may occur
- In part secondary to abnormal metabolism of Calcium and Phosphorus
- However, additional poorly understood, modifying factors are required to trigger Calciphylaxis
V. Risk Factors
- Renal Osteodystrophy (Calcium and Phophorus Metabolism in Chronic Kidney Disease)
- Longterm Hemodialysis
- Hyperparathyroidism
- Female gender
- Caucasian
- Obesity
- Diabetes Mellitus
- Autoimmune disorders (e.g. SLE)
- Hypoalbuminemia
- Malignancy
- Liver disease
- Medications
- Calcium-based Phosphate Binders (e.g. Calcium Carbonate, Calcium acetate)
- Corticosteroids
- Activated Vitamin D
- Warfarin
- Iron Therapy
- Frequent Subcutaneous Injections (e.g. Insulin)
VI. Symptoms
- Severe generalized pain (especially at skin lesions)
VII. Signs
- Tender skin lesions
- Skin lesion distribution (in order of high to low frequency)
- Lower leg
- Upper Leg, thighs and buttocks
- Abdomen
- Distal arms
- Proximal arms
- Skin lesion course
- Red to purple skin lesions, Subcutaneous Nodules and Plaques
- Skin Ulceration
- Skin necrosis and eschar (may be complicated by Cellulitis)
- Associated Findings
- Livedo Reticularis may be present
VIII. Labs
- See Renal Osteodystrophy
- Skin Biopsy
- Precautions
- Calciphylaxis is often a clinical diagnosis that does not require skin biopsy
- Skin biopsy sites may heal poorly and risk infection
- Findings
- Tunica intima layer fibrosis
- Small artery and arteriole calcifications (esp. capillary calcification within adipose tissue)
- Intra-arteriole thrombus may be present
- Dermal and epidermal ulcerations and necrosis
- Precautions
IX. Differential Diagnosis
- Cellulitis
- Vasculitis
- Warfarin Skin Necrosis
- Endarteritis Obliterans
- Antiphospholipid Syndrome
- Cholesterol embolization
X. Management
- Precautions
- Under-recognized condition outside of Hemodialysis centers (missed diagnosis is not uncommon)
- Very high morbidity and mortality
- Pain management
- Pain is severe and debilitating and results in frequent clinical encounters
- Consider Amitriptyline, Pregabalin in addition to Analgesics
-
Renal Osteodystrophy (Calcium and Phophorus Metabolism in Chronic Kidney Disease)
- See Renal Osteodystrophy
- Maintain Serum Phosphate <5.5 mg/dl
- Avoid Hypercalcemia
- Avoid Calcium-based Phosphate Binders
- Avoid Calcium supplements
- Avoid high Calcium dialysate baths (>2.5 meq/L)
- Secondary Hyperparathyroidism
- Maintain Parathyroid Hormone 150 to 300 ng/ml
- Avoid activated Vitamin D
- Calcimimetic agent (e.g. cinacalcet) as needed to lower PTH levels
- Parathyroidectomy may be considered
- Eliminate medications associated with Calciphylaxis
- Replace Warfarin with Direct Acting Anticoagulants (DOACs)
- Skin Lesion Management
- Sodium Thiosulfate IV (infused during Dialysis)
- Sodium Thiosulfate has an unclear mechanism, but has vasodilation and antioxidant properties
- Benefit in >70% of patients
- Nigwekar (2013) Clin J Am Soc Nephrol 8(7):1162-70 +PMID:23520041 [PubMed]
- Wound care
- Debride necrotic, non-viable tissue
- Consider hyperbaric oxygen therapy
- Prevent infection
- Prophylactic Antibiotics are NOT recommended
- Start Antibiotics at first signs of infection
- Sodium Thiosulfate IV (infused during Dialysis)
XI. Complications
- Non-Healing Wounds
- Skin infarction and necrosis
- Cellulitis often associated with Sepsis (primary cause of death)
XII. Course
- Skin ischemia may progress to skin necrosis
- One year survival is <50%
- Mortality typically due to Sepsis
XIII. Resources
- Westphal (2022) Calciphylaxis, StatPearls, Treasure Island (FL)
XIV. References
- Mason and Swaminathan in Swadron (2022) EM:Rap 22(10): 1-3
- Nigwekar (2015) Am J Kidney Dis 66(1):133-46 +PMID: 25960299 [PubMed]