Cutaneous Necrosis From Calcific Uremic Arteriolopathy Toby Coates, MB, BS, FRACP, Geoff S. Kirkland, MB, BS, FRACP, Robert B. Dymock, MB, BS, FRCPA, Brendan F. Murphy, MB, BS, FRACP, John K. Brealey, BAppSci, MedLabSci, Timothy H. Mathew, MB, BS, FRACP, andAlexander P.S. Disney, MB, BS, FRACP ● Calcific uremic arteriolopathy (calciphylaxis) is an uncommon complication of chronic renal failure that is associated with high morbidity and mortality. We report 16 patients (13 female) who presented between 1985 and 1996. All patients developed painful livido reticularis that progressed to cutaneous necrosis and ulceration (11 cases on the proximal extremities and five cases on the distal extremities). Two patients with predominately distal leg disease survived; the cause of death in the other 14 patients was sepsis (six patients), withdrawal from dialysis (three), cardiac arrest (three), and gastrointestinal hemorrhage (two). Mesenteric ischemia from intestinal vascular calcification occurred in two cases. Clinical factors identified included the use of warfarin therapy in seven cases and significant weight loss (G10% body weight) in seven cases in the 6 months preceding the development of calcific uremic arteriolopathy. Skin pathology was studied in 12 cases, with all showing calcific panniculitis and small vessel calcification. Electron microscopic spectral analysis of the mineral content of the calcific lesions in the subcutaneous tissue showed only calcium and phosphorous. In two cases, substitution of low molecular weight heparin for warfarin therapy resulted in clinical improvement. Current theories of pathogenesis and treatment are reviewed. This study confirms the high morbidity and mortality of calcific uremic arteriolopathy producing ischemic tissue necrosis while drawing attention to significant weight loss and warfarin therapy as risk factors for the development of ischemic tissue necrosis. Hyperbaric oxygen therapy warrants further study.  1998 by the National Kidney Foundation, Inc. INDEX TERMS: Calcific uremic arteriolopathy; ischemic tissue necrosis; calciphylaxis; renal failure; warfarin; low molecular weight heparin. Editorial, p. 514 C ALCIFIC uremic arteriolopathy (calciphy- laxis) is a serious life-threatening condi- tion of progressive cutaneous necrosis that oc- curs in patients with chronic renal failure (CRF) who are frequently but not exclusively dialysis dependent or have a failing renal transplant. 1-6 The lesions characteristically occur in the skin of the legs, particularly the buttocks and thighs, 7 but have been reported on the abdomen, in the skeletal muscle, 8,9 and also with acral gangrene. 10,11 The disorder is characterized by the development of a painful livido reticularis that is followed by skin ulceration, which is associated with high morbid- ity and mortality (Fig 1A). Calcific uremic arte- riolopathy has been associated with most pri- mary renal diseases, including diabetes mellitus, 12,13 but it may rarely develop in settings other than renal failure, such as primary hyper- parathyroidism 14 and alcohol-related cirrhosis. 15 Since the largest series of patients with this condition was reported, 10 no uniform consensus concerning pathogenesis or treatment has emerged. In this article, we summarize the clinical course of 16 patients with calcific uremic arteriolopathy (calciphylaxis), 12 of whom had a skin biopsy. We report our experience with treatment and review the available literature on its pathogen- esis and management. PATIENTS AND METHODS Sixteen patients with calcific uremic arteriolopathy (calci- phylaxis) were identified from the renal units of The Queen Elizabeth Hospital, Royal Adelaide Hospital, Flinders Medi- cal Centre, and St Vincent’s Hospital between 1985 and 1996. Case notes and biochemistry were reviewed; skin biopsy specimens were reviewed by one histopathologist (R.B.D.). Biopsy material was subjected to routine tissue processing on a Myles V/P time processing machine (Miles, IN) and embedded in wax, sectioned at 3 μm, and stained with hematoxylin-eosin. Tissue blocks from patients with calcific uremic arterio- lopathy were deparaffinized and processed for electron mi- croscopy. Steps involving osmium tetroxide and uranyl From the Renal Unit and Department of Medicine, Univer- sity of Adelaide, The Queen Elizabeth Hospital Campus, Woodville, South Australia; the Department of Histopathol- ogy, The Queen Elizabeth Hospital, Woodville, South Austra- lia; and the Renal Unit, St Vincent’s Hospital, Melbourne, Victoria, Australia. Received January 12, 1998; accepted in revised form May 22, 1998. Address reprint requests to Alexander P.S. Disney, MB, BS, FRACP, Renal Unit, The Queen Elizabeth Hospital, 28 Woodville Rd, Adelaide, South Australia 5011. E-mail: adisney@tqehsmtp.tqeh.sa.gov.au  1998 by the National Kidney Foundation, Inc. 0272-6386/98/3203-0005$3.00/0 384 American Journal of Kidney Diseases, Vol 32, No 3 (September), 1998: pp 384-391