Calciphylaxis

Abstract: Vascular calcification is highly correlated with cardiovascular disease mortality, especially in patients with ESRD or diabetes. In addition to the devastating effects of inappropriate biomineralization seen in cardiac valvulopathies, calciphylaxis, and idiopathic arterial calcification, vascular calcification is now recognized as a marker of atherosclerotic plaque burden as well as a major contributor to loss of arterial compliance and increased pulse pressure seen with age, diabetes, and renal insufficiency. In recent years, several mechanisms to explain vascular calcification have been identified including (1) loss of inhibition, (2) induction of bone formation, (3) circulating nucleational complexes, and (4) cell death. Alterations in calcium (Ca) and phosphorus (P) balance as seen in patients with ESRD promotes vascular calcification via multiple mechanisms and may explain the alarmingly high levels of cardiovascular disease deaths in these patients. Strategies to control Ca and P levels in patients with ESRD have met with early success in preventing progression of vascular calcification. Whether or not vascular calcification can be reversed is not yet known, but exciting new studies suggest that this may be possible in the future.

Abstract: Background Calciphylaxis is characterized by ischemic cutaneous ulceration, high mortality, and ineffective treatment. Methods We conducted a retrospective study of 64 patients with calciphylaxis (including 49 dialysis patients age- and sex-matched to 98 dialysis controls). Results The estimated 1-year survival rate of calciphylaxis was 45.8%. Risk factors for calciphylaxis included obesity, liver disease, systemic corticosteroid use, calcium-phosphate product more than 70 mg 2 /dL 2 , and serum aluminum greater than 25 ng/mL. Survival rates were similar for 16 patients who received parathyroidectomy and 47 who did not. An estimated 1-year survival rate of 61.6% was observed for 17 patients receiving surgical debridement compared with 27.4% for the 46 who did not ( P = .008). Limitations The study was limited by its retrospective design and there was no control group for the 15 nondialysis cases. Conclusions Calciphylaxis is multifactorial and usually fatal. Prevention of calciphylaxis may include correction of risk factors identified in this study. Surgical debridement was associated with improved survival, but parathyroidectomy was not.

Abstract: Background and objectives: Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis. Design, setting, participants, & measurements: A systematic review of literature for case reports and case series of nonuremic calciphylaxis was performed. Cases included met the operational definition of nonuremic calciphylaxis–histopathologic diagnosis of calciphylaxis in the absence of end-stage kidney disease, renal transplantation, or acute kidney injury requiring renal replacement therapy. Results: We found 36 cases (75% women, 63% Caucasian, aged 15 to 82 yr) of nonuremic calciphylaxis. Primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue disease were the most common reported causes. Preceding corticosteroid use was reported for 61% patients. Protein C and S deficiencies were seen in 11% of patients. Skin lesions were morphologically similar to calcific uremic arteriolopathy. Mortality rate was 52%, with sepsis being the leading cause of death. Conclusion: Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.