Calciphylaxis Risk Factors in Hemodialysis Patients Identified

Researchers linked the condition to warfarin use, diabetes, obesity, recurrent skin trauma, and derangements in mineral metabolism.
Researchers linked the condition to warfarin use, diabetes, obesity, recurrent skin trauma, and derangements in mineral metabolism.

Researchers have identified risk factors for calciphylaxis in hemodialysis (HD) patients that could be useful in directing the design of preventive strategies for this life-threatening condition, according to a paper published online ahead of print in the Journal of the American Society of Nephrology.

In a study of HD patients with newly diagnosed calciphylaxis, also called calcific uremic arteriolopathy (CUA), Sagar U. Nigwekar, MD, of Harvard University Medical School and Massachusetts General Hospital in Boston, and colleagues found that warfarin use, diabetes mellitus, higher body mass index (BMI), higher levels of serum calcium, phosphorus, and parathyroid hormone (PTH), and use of nutritional vitamin D, cinacalcet, and warfarin treatments were independently associated with increased risk of calciphylaxis development in multivariable analysis.

The study included 1,030 HD patients with calciphylaxis (67% women, 49% white, 28% black, and 23% other races) who were matched by age, sex, and race to 2,060 HD patients without calciphylaxis. The median duration between HD initiation and development of calciphylaxis was 925 days. The mortality rates were 27% and 45% at 6 and 12 months after calciphylaxis diagnosis, respectively. The median time to death was 151 days from calciphylaxis diagnosis.

Warfarin use at HD initiation was associated with a greater than 3-fold increased risk of calciphylaxis, and diabetes was associated with a greater than 2-fold increased risk.

At HD initiation, the risk of calciphylaxis increased by 38% for each 5 kg/m2 increment in BMI, 33% with each 1 mg/dL increment in albumin-correct serum calcium, 11% with each 1 mg/dL increment in serum phosphorus, and 12% with each 100 pg/mL increment in PTH. The use of nutritional vitamin D and cinacalcet at HD initiation each was associated with 2-fold increased risk.

Additionally, compared with diabetics receiving no insulin injections, patients who injected insulin 1 or 2 times per day had 49% increased risk, whereas those injecting 3 times per day and more than 3 times per day had 88% and >3.5-fold increased risk, respectively of calciphylaxis at the typical sites of insulin injections suggesting a possible relationship between recurrent skin trauma and calciphylaxis risk.

Dr Nigwekar's team concluded that “risk factors for CUA are present months to years prior to CUA development in patients receiving hemodialysis. CUA has a predilection for white, female, diabetic, and obese patients and, especially in these patients, research and clinical attention should focus on avoiding additional CUA triggers such as vitamin K antagonism or deficiency, skin trauma, and mineral bone deficiencies.”

To conduct this large-scale investigation of calciphylaxis, a rare disease, Dr Nigwekar collaborated with investigators from the Fresenius Medical Care North America, a large dialysis organization and through this collaboration could identify more than 1,000 patients diagnosed with calciphylaxis.

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