MO751: Calciphylaxis is Characterized by Pyrophosphate Deficiency in Dialysis Patients: A Pilot Study

Abstract BACKGROUND AND AIMS Calciphylaxis is a rare but devastating disorder predominantly affecting patients with end-stage kidney disease [1]. Patients with calciphylaxis present with painful ischemic skin lesions caused by microvascular occlusion secondary to calcification, intimal hyperplasia, and thrombosis. In experimental models and in genetic disorders of mineralization, deficiency of pyrophosphate (PPi) results in vascular calcification and neointimal formation [2–4]. We investigated the role of PPi deficiency in the development of calciphylaxis and explored whether PPi levels predict outcomes among patients with calciphylaxis. METHOD As part of the ongoing national-level calciphylaxis registry work (ClinicalTrials.gov Identifier: NCT03032835) [5], we prospectively enrolled 14 dialysis-dependent patients with calciphylaxis (cases) and 7 dialysis-dependent patients without calciphylaxis (controls) matched for age, sex and race. Clinical data and blood samples were collected at enrolment. PPi levels were measured using an ATP Sulfurylase/Luminescence-Based Method for the quantification of inorganic PPi in human plasma and were compared between cases and controls using the Kruskal–Wallis test. Associations between PPi levels and clinical outcomes (ulcer formation, number of skin lesions and 1-year mortality) were explored. RESULTS The average age of calciphylaxis cases and controls was 62 and 61 years, respectively; 53% were women and 53% were Caucasian. The prevalence of diabetes mellitus, obesity, coronary artery disease and peripheral arterial disease were 71%, 23%, 29% and 53%, respectively and comparable between cases and controls. Warfarin exposure was present in 19% of cases. Most patients with calciphylaxis had ulcerated skin lesions involving abdominal wall and/or thighs. Median number of calciphylaxis skin lesions was 2 [interquartile range (IQR) 1–4]. Serum levels of calcium, phosphate, intact parathyroid hormone, 25-OH vitamin D and alkaline phosphatase were similar between cases and controls. Compared with controls, however, patients with calciphylaxis had lower plasma PPi levels [0.32 μM (IQR 0.19–0.70) versus 0.64 μM (IQR 0.46–1.08); P = 0.03]. Plasma PPi levels demonstrated a modest correlation with skin lesion count (r = –0.35) but were similar between patients with and without ulcer formation. Lower plasma PPi levels predicted 1-year mortality (Fig. 1). CONCLUSION In this pilot study, dialysis-dependent patients with calciphylaxis had lower levels of plasma PPi compared with controls. Plasma PPi levels predicted 1-year mortality among patients with calciphylaxis. Additional data from a larger study and longitudinal assessments of PPi levels are needed to support future clinical intervention trials targeting the PPi pathway in calciphylaxis.