Calcium use increases risk of calciphylaxis: a case-control study. (1/61)

OBJECTIVE: To investigate the risk factors for the development of calciphylaxis in renal failure, a poorly understood and often fatal condition characterized by calcium deposition in tissues. DESIGN: Retrospective case-control study. SETTING: University hospital peritoneal dialysis center. PATIENTS: Eight continuous ambulatory peritoneal dialysis (CAPD) patients with calciphylaxis were identified in a 3-year period. We matched up to five controls for dialysis modality and length of time on dialysis with each case. STATISTICS: Multivariate conditional logistic regression analysis for matched case-controls. MAIN OUTCOME MEASURES: Laboratory data and demographics were collected as well as cumulative calcium and vitamin D ingestion over the year prior to disease onset. RESULTS: All the patients were female, versus only 38% (14/37) of controls (p < 0.0001). While not statistically significant, a majority of the patients were diabetic [62.5% (5/8) vs 32% (12/37)]. Peak and average levels of serum calcium, phosphate, calcium x phosphate product, parathyroid hormone (PTH), albumin, iron, total iron-binding capacity (TIBC), and ferritin were not significantly different in cases compared with controls. The use of calcitriol alone or with calcium carbonate was not found to be a significant risk factor for the development of calciphylaxis. In a multivariate analysis, iron intake seemed to be protective, contrary to previous reports, while the use of calcium carbonate was associated with a strong trend to increased risk of calciphylaxis development (odds ratio = 1.029/g and 1.011/g calcium ingested per month, at 1 and 2 - 3 months prior to calciphylaxis development; p = 0.0556 and 0.0565, respectively). CONCLUSION: These data, although limited by the small numbers of index cases, suggest that calcium ingestion is a risk factor for calciphylaxis. The increased use of calcium salts as a phosphate binder in recent years might explain the apparent increased incidence of calciphylaxis in our and other centers. The preponderance of female diabetics among cases reported elsewhere was confirmed in our study.  (+info)

Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. (2/61)

Calciphylaxis (CPX), an uncommon syndrome characterized, in part, by progressive cutaneous vascular calcification, is seen principally in the setting of renal failure-associated hyperparathyroidism and is difficult to distinguish histologically from other microvasculopathies. We assessed histologic specimens from 13 cases of clinicopathologically classic CPX of the skin and reviewed documented histologic findings in the literature. Our series included 7 "early" and 6 "late" lesions (absence or presence of tissue necrosis, respectively). Histologically, early lesions were subtle and almost inapparent microscopically. Late lesions were easier to recognize because of obvious epidermal ulceration, dermal necrosis, and easily seen mural vascular calcification. The most common finding in both groups was acute and chronic calcifying septal panniculitis. Endovascular fibroblastic proliferation was more common in advanced lesions. Necrosis of dermal collagen was identified in only a few early lesions. Frank luminal vascular thrombosis was infrequent in both groups. The cited histologic findings largely were mirrored by those in the literature. Although they are relatively nonspecific when considered in isolation, the cited histopathologic features of cutaneous CPX allow for the diagnosis of this potentially lethal disorder when they are seen in combination with one another, particularly if detailed clinical data also are available.  (+info)

Risk factors and mortality associated with calciphylaxis in end-stage renal disease. (3/61)

BACKGROUND: We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in end-stage renal disease. METHODS: Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. RESULTS: Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI, 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI, 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis, for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001). CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase, and low serum albumin are risk factors for calciphylaxis. Calciphylaxis is associated with a very high mortality.  (+info)

Calciphylaxis. (4/61)

The phenomenon of calciphylaxis is rare, but potentially fatal. It has been recognised for a long time in patients with chronic renal failure with secondary hyperparathyroidism. Disturbed calcium and phosphate metabolism can result in painful necrosis of skin, subcutaneous tissue and acral gangrene. Appearance of the lesions is distinctive but the pathogenesis remains uncertain. The beneficial effects of parathyroidectomy are controversial. However, correction of hyperphosphataemia or occasionally hypercalcaemia is imperative. Fulminant sepsis as a consequence of secondary infection of necrotic and gangrenous tissue is a frequent cause of patient morbidity and mortality.  (+info)

Hyperbaric oxygen in the treatment of calciphylaxis: a case series. (5/61)

BACKGROUND: Calciphylaxis, also referred to as calcific uraemic arteriolopathy, is a syndrome associated with end-stage renal disease (ESRD), and causes necrotic skin ulcers, often leading to a fatal outcome. Hyperbaric oxygen (HBO(2)) therapy has been used to enhance wound healing, but its role in the treatment of calciphylaxis is unclear. METHODS: We undertook a retrospective study of patients on renal replacement therapy with biopsy-proven calciphylaxis who were treated with HBO(2) between March 1997 and February 2000. RESULTS: Five patients were treated with HBO(2): three patients were on continuous ambulatory peritoneal dialysis (CAPD) and two were on chronic haemodialysis therapy. None of the patients had uncontrolled hyperparathyroidism and none underwent parathyroidectomy. The patients each received 25-35 treatments of HBO(2) at 2.5 atmospheres for 90 min per treatment. Two of these patients had complete resolution of extensive necrotic skin ulcers, with no adverse effects of HBO(2) therapy. Both had improvement in wound area transcutaneous oxygen pressure (P(tc)O(2)) with administration of 100% oxygen when measurements were taken at normobaric and hyperbaric pressures. In the other three patients receiving HBO(2), the skin lesions did not resolve. P(tc)O(2) was measured in two of these patients, neither of whom showed improvement with 100% oxygen administered at normobaric pressure. CONCLUSIONS: The data support a role for HBO(2) in the treatment of some patients with calciphylaxis, particularly as in the absence of uncontrolled secondary hyperparathyroidism there are few therapeutic options.  (+info)

Healing of skin necrosis and regression of anticardiolipin antibodies achieved by parathyroidectomy in a dialyzed woman with calcific uremic arteriolopathy. (6/61)

AIM: To present the impact of parathyroidectomy on the spontaneous healing of necrotic lesions of the skin of the lower leg and on anticardiolipin antibodies regression in a 68-year-old female dialyzed patient with hyperparathyroidism and calcific-uremic arteriolopathy (CUA). METHODS: After the occurrence of initial lesions of the lower leg skin, the intact parathyroid (iPTH) level, calcium (Ca) and phosphorus (P) product were measured, and on two occasions at 6-week intervals, the titer of anticardiolipin antibodies was determined, followed by a clinical monitoring of the progress of necrotic skin lesions. Two months after the occurrence of the skin lesions, the patient's right leg was amputated below the knee due to gangrene, and a histopathological analysis of the skin tissue sample of the amputated lower leg was made. After parathyroidectomy, iPTH, Ca x P product were measured, and on two occasions at 6 weeks' intervals, anticardiolipin antibodies titer was determined, followed by a clinical monitoring of lesions of the left lower leg skin. RESULTS: Before parathyroidectomy, iPTH level and Ca x P product were increased, as well as IgG anticardiolipin antibody titer measured on two occasions 6 weeks apart. The histopathological analysis of the skin tissue sample of the amputated right lower leg showed mural calcification of artery walls and thrombotic occlusions of small arteries, arterioles, and dermal capillaries, in addition to epidermolysis. A week after parathyroidectomy, iPTH level and Ca x P product were within normal range. Two measurements 6 weeks apart revealed no anticardiolipin antibodies. Eight weeks after parathyroidectomy, spontaneous healing of necrotic skin lesions of the left lower leg was observed. CONCLUSION: Regression of anticardiolipin antibodies, normalization of Ca x P product, and healing of the skin lesions after parathyroidectomy all pointed to the elevated PTH level as a crucial factor in the pathogenesis of CUA.  (+info)

Calciphylaxis in a patient with end-stage renal disease secondary to systemic lupus erythematosus associated with acral gangrene and mesenteric ischemia. (7/61)

A patient with end stage renal disease secondary to systemic lupus erythematosus (SLE) ultimately required amputation of the four extremities and developed mesenteric ischemia. The patient presented with widespread medial calcification involving various small to medium sized arteries, although no noticeable secondary hyperparathyroidism was observed. We speculated that SLE associated with systemic vasculitis and uremic milieu over a number of years may represent the perfect preexisting condition for calcific arteriolopathy to occur following which several factors including chronic administration of corticosteroids, photosensitivity in lupus, and significant weight loss may have contributed to acral gangrene and mesenteric ischemia.  (+info)

Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. (8/61)

BACKGROUND: Calciphylaxis, historically considered rare, seems to be increasing in frequency. In our single center, 36 new cases have accumulated in seven years. The majority of these cases were non-ulcerating, which we believe to be early disease, in contradistinction to the vast majority of published cases that presented with ulcers. METHODS: Prospective data were collected on all patients with calciphylaxis. As well, a case control study, with two controls per patient, was performed on patients presenting with non-ulcerating plaques. RESULTS: The incidence of calciphylaxis in dialysis patients increased with a rate of 4.5/100 patient-years in the past three years. Eighty percent of cases presented with non-ulcerating subcutaneous plaques in the calves, easily confused with cellulitis. In those patients presenting with plaques only, the mortality rate was 33% at six months. Once ulceration develops, the mortality rate increased to above 80%. Bone scan was positive in 97% of patients. Steroid therapy appeared to be beneficial in some patients. Peritoneal dialysis, female sex and diabetes were risk factors. In the case control study of patients presenting with plaques only, serum phosphate (OR 2.6; 95% CI 1.05 to 6.45, P = 0.038) and Ca x P product (OR 1.46; 95% CI 1.02 to 20, P = 0.038) predicted the disease, as did being on calcium salts + vitamin D (OR 4.05; 95% CI 1.14 to 14.5, P = 0.03). CONCLUSIONS: Calciphylaxis is no longer rare. It is usually nonulcerating and can be diagnosed clinically in all patients. These patients have a high mortality, especially once ulceration occurs. Calcium salts plus vitamin D, as well as serum Ca x P product and high serum P increase the chance of the diseases. Therefore, the disease may be preventable. Steroids may be of benefit to some patients.  (+info)

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