Calciphylaxis in Uraemic and Non- Uraemic Settings: Clinical Risk Factors and Histopathologic Findings.

BACKGROUND Calciphylaxis is a life-threatening cutaneous ulcerative/necrotic disease characterised by vascular calcification/occlusion. It occurs most commonly in end-stage kidney disease (ESKD) (uraemic calciphylaxis; UC) but can also occur in patients with chronic kidney disease (CKD) and normal kidney function (non- uraemic calciphylaxis; NUC). Large series of NUC are limited in the literature. OBJECTIVE To compare the clinicopathologic features of UC and NUC. METHODS We retrospectively compared the clinicopathological features of 35 patients with NUC from 2010-2020 with 53 patients with UC as controls. Cases were classified as NUC in the absence of all of the following: ESKD, a significant CKD defined as serum creatinine >3 mg/dl or creatinine clearance <15 ml/min, acute kidney injury requiring kidney replacement therapy, or kidney transplantation. RESULTS NUC represented 40% of the total cases and showed more female predominance (p-value= 0.005) and a higher median body mass index (p-value = 0.06). Elevated parathyroid hormone was present in 44% of patients with NUC. Most tested patients were positive for lupus anticoagulants (56%). NUC biopsies showed a higher rate of extravascular calcium deposits (73% vs 47%, P-value = 0.03). Dermal reactive vascular proliferation was the most common dermal change (32%). CONCLUSIONS NUC is more common than previously reported and shows higher predilection for obese postmenopausal females. Undiagnosed hyperparathyroidism shows a possible association with NUC. Lupus anticoagulants were positive in most patients. NUC biopsies are more likely to display extravascular calcium deposition than UC biopsies.