Combination of Sodium Thiosulphate, Cinacalcet, and Paricalcitol in the Treatment of Calciphylaxis with Hyperparathyroidism

Kyritsis, Ilias; Gombou, A..; Griveas, Ioannis; Agroyannis, Ioannis; Retsa, Kalliopi; Agroyannis, B.

doi:10.1177/039139880803100809

Cited by 27 publications

(18 citation statements)

References 9 publications

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“…3,8 Several strategies aimed at treating and preventing this affliction in the nondialysis population have been reported in the literature. These include early parathyroidectomy, 5,7 sodium thiosulfate, 8,9 vitamin D analogs, 9 bisphosphonates, 10 cinacalcet, 10,11 and hyperbaric oxygen. 12 Unfortunately, none of these maneuvers have been shown to be universally beneficial and the outcome for most patients afflicted with calciphylaxis remains quite poor.…”

Section: Discussionmentioning

confidence: 99%

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Brucculeri¹,

Haydon²

2011

IJNRD

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Calciphylaxis is a disabling and life-threatening complication that primarily affects patients who are dialysis dependent. Reports have grown in the literature of cases occurring in those who have advanced chronic kidney disease (pre-end-stage renal disease) or in the setting of transplantation. There are also a few reports of cases occurring in those without any form of chronic kidney disease but with primary hyperparathyroidism. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels that result in necrotizing, nonhealing ulcers -many of which are life threatening. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe a patient with comparatively early stage-3 chronic kidney disease who developed calciphylaxis in the setting of both primary and secondary hyperparathyroidism. Predictably, after subtotal parathyroidectomy, her wounds did not completely heal and her biochemical markers of hyperparathyroidism did not completely normalize until her underlying secondary hyperparathyroidism was treated medically. It was only after initiating cinacalcet that the patient experienced complete wound healing and resolution of her calciphylaxis. It also supports other authors' findings that cinacalcet may be an important adjunct in the treatment of calciphylaxis. Keywords: calciphylaxis, chronic kidney disease, cinacalcet, parathyroidectomy Case reportA 66-year-old Caucasian woman with a medical history significant for chronic kidney disease (CKD) stage 3, hypertension, and morbid obesity was followed regularly at our nephrology and hypertension clinic. She was being treated aggressively for her hypertension, proteinuria, hyperuricemia, and secondary hyperparathyroidism (SHPT). Her baseline creatinine fluctuated between 1.5 mg/dL and 2.0 mg/dL, and eGFR (6 variable Modification of Diet in Renal Disease) between 24 and 34 mL/min/1.73 m 2 . Her home medications included paricalcitol, gemfibrozil, febuxostat, pantoprazole, furosemide, lisinopril, latanoprost ophthalmic, and ferrous sulfate. Our patient had never taken warfarin, vitamin D, or any oral phosphate binders. In 2009, her intact parathyroid hormone (PTH) levels were noted to be rising despite her receiving oral paricalcitol 1 mcg daily. The dose was eventually adjusted up to 2 mcg daily without controlling her PTH which climbed as high as 216 pg/mL. Her calcium levels climbed from 9.0 to 10.4 mg/dL but never higher. Her serum phosphorous levels ranged from 2.9 to 3.7 mg/dL before, during, and after subsequent treatment. Most importantly, the Ca 2+ × PO 4 2-solubility product was never greater than 33.7. In August 2010, she presented with painful eruptions and ulcerations along the medial aspects of her thighs Dovepress submit your manuscript | www.dovepress.com

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Section: Discussionmentioning

confidence: 99%

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Brucculeri¹,

Haydon²

2011

IJNRD

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“…Cinacalcet has been successfully used in several patients with CUA (22,(51)(52)(53)(54)(55). VDRAs increase the risk of developing hypercalcemia or hyperphosphatemia; however, they have been used successfully in combination with cinacalcet (54,56,57).…”

Section: Managementmentioning

confidence: 99%

“…Reports of sodium thiosulfate used to treat CUA first appeared in 2004 (51). There has since been numerous case reports and small series demonstrating effective treatment of CUA with the addition of sodium thiosulfate to the treatment regimen (22,38,(52)(53)(54)(55)(58)(59)(60)(61). Sodium thiosulfate is a chelating agent that has antioxidant activity and increases activity of endothelial nitric oxide synthetase (22); it has been used to treat cyanide toxicity, to reduce toxicity of cisplatin chemotherapy, and to chelate calcium in the treatment of nephrolithiasis (62)(63)(64).…”

Section: Managementmentioning

confidence: 99%

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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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“…Furthermore, favourable outcome was recorded in limited reports on CUA using cinacalcet or parathyroidectomy to achieve targeted normalised calcium, phosphate, and parathyroid hormone levels [8, 9]. Yet usefulness of these agents in the form of combination therapy has not been fully explored [10, 11]. The aim of the study was to review all cases of CUA seen in the last five years and determine its clinical course in the setting of multimodality care.…”

Section: Introductionmentioning

confidence: 99%

Calcific Uremic Arteriolopathy on Multimodal Combination Therapy: Still Unmet Goal

Malabu

Manickam

Kan

et al. 2012

International Journal of Nephrology

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Background. Calcific uremic arteriolopathy (CUA) or calciphylaxis though generally noted for its high mortality, recent case reports have shown promising results using single agent therapies. However, it is not clear whether combination therapeutic agents will improve course of the disease. Objective. To determine clinical outcome in subjects with CUA on multimodal treatment. Methods. All patients with end-stage renal failure (ESRF) at The Townsville Hospital, Australia, from April 1, 2006, to March 31, 2011, with diagnosis of CUA were retrospectively studied. Results. Six subjects with CUA (4 females and 2 males) were on various combination therapeutic agents comprising sodium thiosulphate, hyperbaric oxygen, prednisolone, cinacalcet, and parathyroidectomy in addition to intensified haemodialysis, specialist local wound care, and antibiotics. The wounds failed to heal in 3 patients while 5 of the 6 subjects died; cause of death being sepsis in 3 and myocardial infarction in 2. Conclusion. Prognosis of CUA remains poor in spite of multimodal combination therapy. Further prospective studies on a larger population are needed to verify our findings.

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Combination of Sodium Thiosulphate, Cinacalcet, and Paricalcitol in the Treatment of Calciphylaxis with Hyperparathyroidism

Cited by 27 publications

References 9 publications

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Calciphylaxis presenting in early chronic kidney disease with mixed hyperparathyroidism

Painful Skin Ulcers in a Hemodialysis Patient

Calcific Uremic Arteriolopathy on Multimodal Combination Therapy: Still Unmet Goal

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