Management of patients with calciphylaxis: current perspectives

Figures & data

Table 1 Recommendations for possible blood analysis in patients with suspicion of CP. The values marked with * might be restricted to cases with further research interest

Parameter	Comment
Creatinine, serum calcium (total), free (ionized) calcium, phosphate, albumine, parathyreoid hormone, calcium-phosphate product, 25-hydroxyvitamin-D, 1–25-dihydroxyvitamin-D	To exclude/confirm (status of known) renal disease or hyperparathyroidism
Alphafetoin*	Glycoprotein of the liver, inhibiting accumulation of hydroxyapatit formations
Serum cystatin C*	Marker of renal function in early acute renal disease
Osteoprotegerin*, GLA-1 (globular arrest 1) protein*, fibroblast growth factor 23*	Paracrine signal proteins involved in vascular calcification
Standard blood coagulation tests, homocysteine, antiphospholipid antibodies	To exclude coagulation disorders
Antinuclear antibodies, antineutrophilic cytoplasmic antibodies	To exclude collagenoses or vasculitis

Table 2 Overview of risk factors observed for development of CP (data from⁵,⁷)

Chronic kidney disease, hemodialysis, kidney transplant recipient
Hyperphosphatemia
Hypercalcemia
High levels of alkaline-phosphatase Calcium-phosphate product >70 mg^2/dL^2
Secondary hyperparathyroidism
Female gender
BMI >30 kg/m^2
Liver disease
Systemic corticosteroid use
Hypalbuminemia
Warfarin therapy
Serum aluminium >25 ng/mL

Table 3 Therapeutic options for the treatment of CP

Local wound therapy
Debridement	Adapted to extent of necrosis, wound surface area, pain and available method
Modern wound dressings	To maintain atraumatic wound dressing
Antiseptic and antimicrobial effective wound dressings	For prevention or therapy of wound infection
HBOT	Adapted to availability
Systemic (supportive) therapy
Pain medication	Adapted to degree of pain and individual patient’s requirement
Antibiotics	For therapy of wound infection
Cessation of vitamin K-antagonists	Supplement of vitamin K can be considered
Anticoagulation with direct thrombin inhibitors or tissue plasminogen activator	Especially if clues for underlying coagulative disorder can be found.
Systemic therapy (in case of calcium overload)
Optimization of the underlying renal disease
Changes in frequency or duration of dialysis, change of filtration/dialysis system
Calcium-free phosphate binders
Reduction of vitamin D intake
Cinacalcet	When secondary hyperparathyroidism is confirmed
Parathyreoidectomy	When hyperparathyroidism is confirmed
Systemic therapy to reduce calcification
Sodium thiosulfate	Adapted to renal disease or dialysis
Bisphosphonates SNF472	Attention should be paid to possible side effects or contraindications So far only in study protocols

Abbreviation: HBOT, hyperbaric oxygen therapy.

Table 4 Overview of recruiting studies worldwide (data survey on clinicaltrials.gov on 05/06/2019)

clinicaltrials.gov identifier	Title	Study type	Study design	Study substance
NCT03I50420	A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients (CALISTA)	Interventional	Multicentre Randomized Double-blind Placebo-controlled 111 patients planned	Sodium thiosulfate
NCT02278692	Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy (VitK-CUA)	Interventional	Single center Randomized Placebo-controlled 20 patients planned	Vitamin K
NCT02635373	European Calciphylaxis Registry Network (EuCalNet)	Observational	Prospective Registry 1000 patients planned	N.A.
NCT03032835		Observational	Prospective Registry 300 patients planned Observation for 20 years	N.A.

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