A case-control study of calciphylaxis in Japanese end-stage renal disease patients

Matsuhiko Hayashi, Ichiro Takamatsu, Yoshihiko Kanno, Tadashi Yoshida, Takayuki Abe, Yuji Sato
Nephrology, Dialysis, Transplantation 2012, 27 (4): 1580-4

BACKGROUND: Calciphylaxis, also called calcific uremic arteriolopathy, is a rare and often fatal complication of end-stage renal disease and is characterized by painful skin ulceration, necrosis, medial calcification and intimal proliferation of small arteries. Studies in western countries have reported incidences ranging from 1 to 4% in chronic hemodialysis patients. Since no systematic studies of calciphylaxis have ever been performed in Japan, we conducted a nationwide survey and a case-control study to identify the characteristics of calciphylaxis in the Japanese dialysis population.

METHODS: Firstly, we sent a questionnaire to 3760 hemodialysis centers in Japan, asking whether calciphylaxis cases had been encountered in the past, and detailed clinical data regarding each case were then collected from the centers. In addition, two control dialysis patients matched for age and duration of hemodialysis to each calciphylaxis case were identified at the participating centers, and their data were analyzed to identify risk factors for calciphylaxis.

RESULTS: Responses to the questionnaire were obtained from 1838 centers (48.3%), and 151 centers reported that a total of 249 cases had been encountered. Sixty-four centers agreed to participate in the case-control study, and detailed clinical data in regard to 67 cases were obtained. In 28 of the 67 cases, a definite diagnosis of calciphylaxis was made by our study group based on the clinical characteristics and skin biopsy findings. A univariate logistic regression model comparing them with 56-matched controls identified warfarin therapy [odds ratio (OR) 11.4, 95% confidence interval (CI)] 2.7-48.1, P=0.0009], each 1 g/dL decline in serum albumin level (OR 19.8, 95% CI 4.4-89.5, P=0.0001), each 100 mg/dL increment in plasma glucose level (OR 3.74, 95% CI 1.08-12.9, P=0.037) and each 1 mg/dL increment in adjusted serum calcium level (OR 3.2, 95% CI 1.63-6.30, P=0.0008) at the time of diagnosis as significantly associated with calciphylaxis, but no significant associations were found with female gender, vitamin D analog therapy, serum phosphate level, adjusted calcium-phosphate products or serum alkaline-phosphatase level. Warfarin therapy and lower serum albumin levels were still significant risk factors after a multivariate logistic regression model analysis.

CONCLUSION: The results of this study showed that warfarin therapy and lower serum albumin levels are significant and strong risk factors for the development of calciphylaxis in chronic hemodialysis patients in Japan.

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