Calciphylaxis in the current era: emerging 'ironic' features?

Farah, Myriam; Crawford, Richard; Levin, Adeera; Yan, Clifford Chan

doi:10.1093/ndt/gfq407

Cited by 50 publications

(47 citation statements)

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“…• Thus, patients treated with warfarin may have a diminished capacity to inhibit vascular calcification due to deceased amounts of active forms of these proteins [1,7]. Primary coagulation disorders implicated include protein S and C deficiency, the antiphospholipid syndrome, vitamin K deficiency, and AT3 deficiency [7].…”

Section: Citation: Higgins S Hu M Worswick S Binder S (2016) Calcimentioning

confidence: 99%

“…Primary coagulation disorders implicated include protein S and C deficiency, the antiphospholipid syndrome, vitamin K deficiency, and AT3 deficiency [7].…”

Section: Citation: Higgins S Hu M Worswick S Binder S (2016) Calcimentioning

confidence: 99%

“…More novel approaches target alteration of osteoprotegrin and NF-κB pathways and treatment of macrophage and cytokine-mediated inflammation [4]. Although iron has not been definitively proven to be an etiologic agent in development of calciphylaxis, iron products should be stopped nonetheless due to recent reports of its possible role in pathogenesis [6,7]. Targeted molecular therapies may also play a role in treatment or prevention.…”

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confidence: 99%

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Calciphylaxis and Hypotension: Report of a Case and Review of the Literature

Higgins¹

2016

CDT

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Section: Citation: Higgins S Hu M Worswick S Binder S (2016) Calcimentioning

confidence: 99%

“…Primary coagulation disorders implicated include protein S and C deficiency, the antiphospholipid syndrome, vitamin K deficiency, and AT3 deficiency [7].…”

Section: Citation: Higgins S Hu M Worswick S Binder S (2016) Calcimentioning

confidence: 99%

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confidence: 99%

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Calciphylaxis and Hypotension: Report of a Case and Review of the Literature

Higgins¹

2016

CDT

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“…Use of calcium supplements has been associated with increased risk of calciphylaxis in some (19,24), but not, all studies (7,17). Recent studies have suggested that parenteral iron may also be associated with development of CUA (25,26).…”

Section: Risk Factorsmentioning

confidence: 99%

Painful Skin Ulcers in a Hemodialysis Patient

Sprague

2014

Clinical Journal of the American Society of Nephrology

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SummaryCalciphylaxis, also referred to as calcific uremic arteriolopathy, is a relatively rare but well described syndrome that occurs most commonly in patients with late stage CKD. It is characterized by very painful placques or subcutaneous nodules and violaceous, mottled skin lesions that may progress to nonhealing ulcers, tissue necrosis, and gangrene with a 1-year mortality rate >50%. The pathogenesis of calciphylaxis is poorly understood. Risk factors include female sex, obesity, hyperphosphatemia, hypercalcemia, hyperparathyroidism, longer dialysis vintage, hypercoagulable states, and use of calcium-containing phosphate binders and warfarin. Treatment strategies for calciphylaxis are limited by inadequate understanding of its pathophysiology. Therapy is generally focused on correcting disturbances of calcium, phosphorus, and parathyroid hormone metabolism. Additional therapy focuses on decreasing inflammation and on dissolution of tissue calcium deposits with sodium thiosulfate and/or bisphosphonates. Successful treatment generally results in improvement of pain and healing of the lesions within 2-4 weeks, but the disorder generally takes many months to completely resolve.Clin J Am Soc Nephrol 9: 166-173, 2014. doi: 10.2215/CJN.00320113Case Description Abhijit Naik, MD (Renal Fellow). A 54-year-old white man was referred from an outside dialysis clinic for evaluation of necrotic skin lesions. He had a 10-year history of diabetes and hypertension, with ESRD secondary to diabetes. His history was also significant for coronary artery disease, with two prior myocardial infarctions and atrial fibrillation. He had been undergoing thrice-weekly hemodialysis for 2 years with a Kt/V between 1.3-1.4. Three months before presentation he noticed several small firm and very painful nodules on both anterior thighs. He stated that after several weeks the lesions became much larger, black, and spread to the lateral thighs and buttocks. He was treated with mupirocin ointment and a vascular evaluation revealed normal blood flow in his legs. Aside from these painful lesions, he stated that he generally felt "ok." Dialysis had been proceeding without problems. He denied chest pain, dyspnea, abdominal pain, or any gastrointestinal complaints. Review of systems was otherwise unremarkable. He never smoked and drank alcohol very infrequently. Medications included aspirin, amiodarone, simvastatin, famotidine, glipizide, clopidogrel, sevelamer carbonate, hydrocodone, and gabapentin. He had no known allergies.On examination his vital signs were as follows: temperature, 98.8°F; heart rate, 80 beats per minute; BP, 94/60 mmHg, with no orthostatic changes; and respiratory rate, 20 breaths per minute. His BP was generally low, with systolic BP averaging between 90 and 100 mmHg. He was an ill appearing male in mild distress from extremity pain. His lungs were clear and a cardiovascular examination revealed a regular rate and rhythm with a 2/6 holosystolic murmur. His abdomen had normal bowel sounds and was mildly distended with some asc...

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“…It is characterized by vascular and other soft tissue calcification, intimal hypertrophy, and thrombosis of small vessels, which result in necrotizing nonhealing ulcers with a high risk of sepsis (1,2). Although the pathogenesis of calciphylaxis is not well understood, the contributing factors include hypercalcemia, hyperphosphatemia, hyperparathyroidism, use of calcium containing phosphate binders, hypercoagulability, and warfarin therapy.…”

Section: Introductionmentioning

confidence: 99%

Simulation-Based Sodium Thiosulfate Dosing Strategies for the Treatment of Calciphylaxis

Singh

Derendorf

Ross

2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Calciphylaxis remains a poorly understood life-threatening disorder with limited therapeutic options. Sodium thiosulfate (STS) has reported efficacy, thought to be because solubilizing calcium deposits promote clearance by hemodialysis (HD). Lack of rigorous pharmacokinetic studies makes it problematic for determining proper STS dosing given the expanding range of dialysis prescriptions and intensities.Design, setting, participants, & measurements The purpose of this study was to determine the dosing strategies for STS during different dialysis regimens. Given reported successes using an empiric 25 g, intravenous, 3 times per week after HD, simulations were performed to predict dosing guidelines for alternative, more or less intense dialysis to produce equivalent area under the curve drug exposure. The modeled prescriptions varied HD time from 12 to 40 h/wk over three to six sessions (Q b 200 to 400 ml/min, Q d 500 to 800 ml/min), and continuous venovenous hemodialysis at low flow rates (Q b 100 to 200 ml/min, Q d 35 to 50 ml/min), using high-flux polysulfone hemofilters. ResultsSimulations showed a marked variation in STS doses depending on HD frequency and duration. Blood and dialysate flows have a less prominent effect. Assuming no residual renal function, HD prescription permutations caused the dose to vary from 72 to 245 g/wk (70-kg adult), and the simulations provide specific guidelines for clinicians. ConclusionsBased on the success reported for one STS dosing regimen and assuming area under the curve exposure of STS is proportional to its effect, pharmacokinetic simulations can be used to calculate the dose for alternative, higher or lower intensity dialysis regimens. These strategies are imperative to assure adequate treatment for this mortal disease, as well as to avoid toxicity from excess dosing.

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Calciphylaxis in the current era: emerging 'ironic' features?

Cited by 50 publications

References 25 publications

Calciphylaxis and Hypotension: Report of a Case and Review of the Literature

Calciphylaxis and Hypotension: Report of a Case and Review of the Literature

Painful Skin Ulcers in a Hemodialysis Patient

Simulation-Based Sodium Thiosulfate Dosing Strategies for the Treatment of Calciphylaxis

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