Abstract

Calciphylaxis is a rare disorder usually affecting patients with end-stage renal disease (ESRD) on dialysis. Recent studies have shown that vascular thrombosis significantly contributes to calciphylaxis, and anticoagulation may be important. We conducted a 15-patient retrospective case control study with clinical and histopathologic findings consistent with calciphylaxis to explore the role of complement mediated endothelial cell injury. Patients ranged from 33-78 years old (mean: 55) and 9 (60%) were female. Fourteen patients had ESRD, of which 11 (79%) were on chronic dialysis. Type II diabetes, associated with complement activation, affected 11 (79%) patients. The lower extremities were most involved, with 9 (60%) patients having disease at additional sites. Nine were on anticoagulation, of which 7 (47%) had a history of a hypercoagulable state. Biopsy samples from 9 (60%) patients showed subcutaneous pauci-inflammatory thrombi within capillaries with or without endothelial and subendothelial calcification. The subcuticular arterioles and small arteries demonstrated variable intimal expansion by calcium and collagen, hence defining an obliterative fibrointimal calcific arteriopathy. In many cases there was incidental metastatic calcification localized to dermal and subcutaneous elastic tissue. We hypothesize that significant endothelial cell injury mediated by C5b-9 is likely pathogenetically significant to the development of calciphylaxis especially in diseases like diabetes mellitus where glycosylation of CD59 leads to unchecked vascular C5b-9 deposition. Immunohistochemistry for C5b-9 will be performed to evaluate complement deposition in these patients. Excessive deposits of microvascular C5b-9 would provide a premise for the utilization of anti-C5 therapy as a novel pathway of therapeutic intervention.