Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control study.

INTRODUCTION: Calciphylaxis is a rare but potentially fatal disease commonly occurred in dialysis patients. Despite some previous studies on risk factors for calciphylaxis, there is still a lack of data from Chinese population. METHODS: The retrospective matched case-control study about calciphylaxis was performed in Zhongda Hospital affiliated to Southeast University. The case group involved 20 hemodialysis patients who were newly diagnosed with calciphylaxis from October 2017 to December 2018. The 40 noncalciphylaxis patients undergoing dialysis with the same age and duration of dialysis were randomly selected as controls. RESULTS: Most of calciphylaxis patients were male and elderly, while overweight people were more susceptible to the disease. Although incidence of secondary hyperparathyroidism was higher in calciphylaxis patients, the differences in duration of elevated serum intact parathyroid hormone (iPTH) and its highest value did not reach statistical significance compared with controls. No significant difference in warfarin therapy was discernible between two groups. The univariate regression analysis indicated that male, score of use of activated vitamin D and its analogues, corrected serum calcium level, serum phosphate, Ca × P product, iPTH, albumin, and alkaline phosphatase (ALP) level were significantly associated with calciphylaxis. Elevated levels of serum phosphate (OR 4.584, p = 0.027) and ALP (OR 1.179, p = 0.036), decreased level of serum albumin (OR 1.330, p = 0.013) were independent risk factors after multivariate analysis. CONCLUSION: This is the first report of risk factors associated with calciphylaxis in China. Increased levels of serum phosphate and ALP, decreased level of serum albumin were vital high-risk factors for calciphylaxis in Chinese hemodialysis population.

The Successful Use of Apixaban in Dialysis Patients with Calciphylaxis Who Require Anticoagulation: A Retrospective Analysis.

Calciphylaxis is a disease of dermal arteriolar calcification that results in necrosis. It commonly occurs in individuals with end-stage renal disease (ESRD) on hemodialysis and is associated with a high morbidity and mortality. Warfarin use is an identified risk factor. Twenty patients with ESRD on dialysis with calciphylaxis who were treated with apixaban for indications of deep vein thrombosis or atrial fibrillation were identified. There were no reports of thrombosis. Three individuals experienced bleeding requiring a transfusion, and anticoagulation was resumed without further event. Findings suggest that apixaban may be a safe and effective alternative to warfarin in patients with ESRD on dialysis with calciphylaxis.

A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma.

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.

Falsely increased chloride and missed anion gap elevation during treatment with sodium thiosulfate.

BACKGROUND: Sodium thiosulfate (STS) is used to treat calciphylaxis and cyanide poisoning, but can lead to a serious anion-gap acidosis. We suspected that the calculated anion gap in a patient treated with STS for calciphylaxis was decreased to normal by a falsely increased chloride, and we hypothesized that STS directly interfered with chloride measurements. METHODS: Plasma pools were prepared with 12 concentrations of STS from 0 to 20 mmol/l. Chloride was measured in each sample on 9 analyzers: Architect 16200, StatProfile pHOx Plus, RapidLab 1265®, Vitros 350®, Advia 1800, Roche Modular, iSTAT1, RAPIDpoint 500, and Radiometer ABL735. RESULTS: Statistically significant, dose-dependent increases in reported chloride concentrations were seen with all analyzers except the RAPIDpoint 500 and Vitros. The increases ranged from 5 to 75 mmol/l at the peak thiosulfate concentrations (33 mmol/l) expected in treated patients. The CLIA-allowable error of 5% was exceeded by 4 analyzers (Architect 16200, iSTAT1, StatProfile pHOx Plus, and Radiometer ABL735). The RAPIDpoint 500 showed a 3-mmol/l decrease in measured chloride over the tested range. The Vitros analyzer showed no interference. CONCLUSIONS: Interference of STS in chloride measurement in several common analyzers may lead to erroneous anion-gap calculations and confound the diagnosis of STS-induced anion-gap acidosis.

Calciphylaxis in a dialysis patient diagnosed by muscle biopsy.

Calciphylaxis is a rare condition seen mostly in patients with chronic renal disease and secondary hyperparathyroidism who develop painful skin lesions and myopathy secondary to extensive small vessel calcification, which leads to tissue ischemia. It is typically diagnosed by a biopsy of prominent skin lesions. Here, we report a 49-year-old man with end-stage renal disease on chronic peritoneal dialysis who presented with weakness, myalgias, and necrotic skin lesions. Multiple skin biopsies were nondiagnostic because of severe extensive necrosis, and the diagnosis of systemic calciphylaxis was eventually made by a muscle biopsy. This case demonstrates the significant muscle involvement in calciphylaxis and highlights the importance of maintaining a high clinical suspicion for patients with risk factors for calciphylaxis, even when skin biopsy does not confirm it.

LDL-apheresis dramatically improves generalized calciphylaxis in a patient undergoing hemodialysis.

We present the first documented case of generalized calciphylaxis that dramatically improved after low-density lipoprotein-apheresis (LA) in a patient undergoing long-term hemodialysis. Calciphylaxis was diagnosed by skin biopsy and was manifest as painful ulcers on the right leg, left buttock, and glans penis. Skin perfusion pressure (SPP), which has recently been used as an indicator of impaired capillary perfusion in distal lesions of the lower extremities, was markedly reduced. The ulcers continued to worsen despite general wound care, correction of levels of calcium × phosphate product, hyperbaric oxygen therapy, and use of bisphosphonate, antiplatelet therapy, and vasodilators. Because LA is known to exert favorable effects on peripheral arterial disease through improved hemorheology, anti-inflammatory action, vasodilation, and angiogenesis, we introduced LA to produce the same effects on calciphylaxis. LA dramatically increased SPP and promoted ulcer healing, demonstrating that LA can be a useful treatment option for calciphylaxis.

Severe anion gap acidosis associated with intravenous sodium thiosulfate administration.

INTRODUCTION: Severe anion gap (AG) acidosis associated with intravenous sodium thiosulfate (STS) administration has not been previously described in nondialysis chronic kidney disease (CKD) patients. CASE REPORT: We present a CKD patient with a baseline creatinine 1.8 mg/dL (eGFR 28 ml/min/1.73 m²) who developed sustained and life-threatening AG acidosis associated with intravenous STS treatment for calciphylaxis. DISCUSSION: Although marketed as a safe drug, STS can cause life-threatening acidosis as illustrated in this case. STS-induced AG acidosis should be considered in the differential diagnosis of severe acidosis in patients receiving STS. Dosage adjustment and close follow-up of patients' acid-base status after STS initiation is necessary.

Successful treatment of calcific uraemic arteriolopathy with bisphosphonates.

BACKGROUND AND OBJECTIVES: Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition that almost exclusively affects patients with chronic kidney disease. Several therapies have been employed to treat this disease but with irregular results. We report a prospective case series of eight patients diagnosed with CUA in our unit between 2002 and 2010. MATERIAL AND METHOD: The series consisted of eight patients with CUA (including 4 men, 5 dialysis patients and 3 with functioning allografts) who were treated with bisphosphonates. The diagnosis was by clinical suspicion and a confirmatory biopsy. Five patients had a previous history of high calcium-phosphorus product, 6 had a history of high parathyroid hormone levels (>800pg/ml), 4 had undergone parathyroidectomy, 5 had a history of high cumulative doses of steroids, and 6 patients were under dicoumarin treatment. None of the patients were obese or had diabetes mellitus. RESULTS: In all patients, progression of skin lesions stopped between 2 to 4 weeks after starting bisphosphonate therapy, with no changes in blood levels of calcium and phosphate. Improvement in pain and lesions was faster in patients receiving intravenous ibandronate. All of these patients remained on bisphosphonate treatment for at least 6 months until the wounds healed completely. No recurrences have been observed after follow-up periods between 1 and 9 years. Renal function remained stable in transplant recipients. The treatment was well tolerated and no adverse effects were observed. CONCLUSIONS: Bisphosphonates could be a new and attractive alternative to treat CUA.

Tumoral calcinosis, calciphylaxis, hyperparathyroidism and tuberculosis in a dialysis patient.

Tumoral calcinosis and calciphylaxis are uncommon but severe complications in uremic patients. They occur generally after long-term hemodialysis (HD) treatment explained by advanced secondary hyperparathyroidism and longstanding high calcium phosphorus product (Ca × P). Other factors such granulomatous diseases may worsen the calcium phosphate homeostasis alterations. We report a young male patient treated by HD for 6 years who developed tuberculosis in addition to tumoral calcinosis and calciphylaxis.

Suspected systemic calcinosis and calciphylaxis in 5 horses.

Five horses were presented with signs of myopathy along with systemic malaise, hyperfibrinogenemia, hyperphosphatemia, and an elevated calcium phosphorus product (Ca*P). Postmortem findings were consistent with systemic calcinosis, a syndrome of calcium deposition in the tissue of organs including lungs, kidneys, muscle, and heart that has not been previously described in horses.

[Calciphylaxis and penile necrosis: a case report and review of the literature ]. / Calcifilassi e necrosi peniena: case report e revisione della letteratura.

INTRODUCTION: Calciphylaxis is a rare clinic condition characterised by skin necrosis due to medial and intimal calcification of small and medium arteries. It's observed in patients affected by end stage renal disease associated to secondary hyperparathyroidism. Penile involvement has been documented in very few cases. We present both a case of penile calciphylaxis and a review of literature, in order to increase comprehension of pathophysiology, diagnosis and therapy of this rare disease. MATERIALS AND METHODS: A retrospective review of literature was performed after treating a case of penile calciphylaxis. We describe patient characteristics, clinical presentation, laboratory and histo-pathologic findings, therapeutic strategy and outcomes of the case. RESULTS: A 65 year-old man, affected by diabetes, chronic ischemic cardiopathy and chronic renal failure in hemodialytic treatment, was referred to our unit for the presence of increased consistency and significative pain of the distal portion of penis evolving in a complete glans necrosis. Blood levels of parathormone (PTH), calcium (Ca) and phosphorous (P) resulted pathologically elevated, promoting tissutal calcium deposition. The patient was treated with partial penectomy and the histologic findings confirm diagnosis of calciphylaxis, showing an ulcerative necrosis of glans with extensive calcium deposition and luminal narrowing of penile small arteries. CONCLUSIONS: The increase of number of patients with chronic renal failure in hemodialytic treatment could make penile calciphylaxis more prevalent in the future. Early diagnosis, lowering of pathologic blood levels of Ca and P associated to surgical treatment of necrotic lesions of the patient could be fundamental for a better prognosis of this aggressive disease.

Calcinosis cutis: a rare reaction to subcutaneous injections of calcium-containing heparin in patients with renal failure.

Calcinosis of the cutis and the subcutis is a rare complication of calcium-containing heparin cutaneous injections, mostly occurring in a context of severe renal failure. We report 2 cases. The first patient developed firm erythematous nodules on his thighs and right arm, in a context of disseminated tuberculosis and acute severe renal failure related to human immunodeficiency virus nephropathy. Cutaneous location of tuberculosis was suspected. Histological features allowed to establish the diagnosis of calcinosis of the cutis and the subcutis, showing violaceous and crackled von Kossa-positive calcium deposits in the whole reticular dermis and in thin collagenous septa of subcutaneous tissue. A retrospective inquiry confirmed that subcutaneous injections of calcium-containing heparin had been performed on the sites where lesions occurred. The second patient developed similar lesions at injection sites of calcium-containing heparin, in a context of non-Hodgkin lymphoma and end-stage renal failure. Similar histological features were observed. Calcinosis of the cutis and the subcutis after subcutaneous injections of calcium-containing heparin is rare. It always occurs in a context of elevated calcium-phosphate product, a situation mostly encountered in severe renal failure. Early cutaneous lesions do not bear specific clinical features.

Determinants of survival in patients with calciphylaxis: a multivariate analysis.

BACKGROUND: Our study aims to assess the factors affecting survival in patients with calciphylaxis. METHODS: We identified 26 patients with biopsy-proven calciphylaxis treated between 1995 and 2007. Clinical and follow-up data were obtained from medical records. Cox proportional hazards models were used to assess the factors affecting survival. RESULTS: The study group consisted of 23 women and 3 men with a mean age of 56.4 +/- 12.9 years. All patients had multiple comorbidities/risk factors including coronary artery disease (58%), diabetes mellitus (58%), and peripheral vascular disease (23%). Mean laboratory values were: calcium, 9.0 mg/dL (range, 6.8-11.6); albumin, 2.8 mg/dL; phosphate, 4.5 mg/dL (range, 2.5-7.5); Ca *phosphate, 35.9; and parathyroid hormone, 320.9 pg/mL (range, 4.6-2,419). Parathyroidectomy was performed in 9 of 26 patients (35%). Of our patients, 19% underwent revascularization procedures and 58% underwent debridement. In multivariate analyses, factors associated with poor survival were female gender ( P = .01), increased weight ( P = .01), and need for vascular procedures ( P = .06). Improved survival was associated with operative debridement ( P = .01). Parathyroidectomy alone did not emerge as a determinant of patient survival, although there was a trend to improved survival when debridement and parathyroidectomy were combined ( P = .09). CONCLUSION: Rather than a single intervention such as parathyroidectomy, a multidisciplinary approach involving early diagnosis, aggressive medical management, operative debridement, and parathyroidectomy may improve survival in calciphylaxis.

Calciphylaxis cutis: a case report and review of literature.

Calciphylaxis is a poorly understood syndrome of vascular calcification and skin necrosis. It affects 1-4% of the population with end stage renal disease (ESRD). Disorders implicated in the pathogenesis of calciphylaxis include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product, and secondary hyperparathyroidism (Essary, L.R. and Wick, M.R. (2000) Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. Am. J. Clin. Pathol. 113, 280-287, Beitz, J.M. (2004) Calciphylaxis:an uncommon but potentially deadly form of skin necrosis. Am. J. Nurs. 104, 36-37.). Although these abnormalities are extremely common in-patients with ESRD, calciphylaxis is relatively rare. The mortality rate of calciphylaxis is about 60-80%. The leading cause of death is sepsis from necrotic skin lesions (Hitti,W.A., Papadimitriou, J.C., Bartlett, S. and Wali, R.K. (2007) Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. Scand. J. Urol. Nephrol.1-3.). Here, we report a case of calciphylaxis in a 23-year-old female with past history of chronic renal failure, renal transplantation and intake of immunosuppressive drug. The relevant literature was discussed.

Surviving calciphylaxis.

Calciphylaxis is a rare disorder with high mortality, which commonly occurs, but not limited to, patients with end-stage renal disease. We present a successful case in which a patient survived this serious disorder of vasculopathy, highlighting the physical and emotional morbidities associated with this condition and alerting physicians of the key elements in its management. Further understanding of calciphylaxis may advance our knowledge in endotheliopathy and vascular ossification.