Calciphylaxis is a life-threatening disorder characterized by occlusion of microvessels in the subcutaneous adipose tissue and dermis. The authors outline the current understanding of calciphylaxis and provide a framework for interdisciplinary management.

Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients.

Background. Calcific uraemic arteriolopathy (CUA, calciphylaxis) is a rare disease predominantly in dialysis patients and associated with high mortality. Painful skin ulcerations and calcification of cutaneous arterioles characterize calciphylaxis. Methods. We established an observational, Internet-based registry allowing online notification for all German CUA cases. The registry recorded data about patient characteristics, biochemistry and therapies. Blood samples were stored in a central biobank. Results. Between 2006 and 2015, 253 CUA patients were recorded: median age 70 [interquartile range (IQR) 61–76] years, 60% females and 86% (n = 207) dialysis patients, translating into an estimated annual incidence rate of 0.04% in German dialysis patients. Fifty-two per cent received vitamin K antagonists (VKAs) prior to CUA. Skin lesions were localized in 71% on the legs or gluteal region. In dialysis CUA patients median total serum calcium was 2.20 (IQR 2.06–2.37) mmol/L, phosphorus 1.67 (IQR 1.35–2.03) mmol/L, intact parathyroid hormone 147 (IQR 72–276) pg/mL and fetuin-A 0.21 (IQR 0.16–0.26) g/L (normal range 0.35–0.95). Median sclerostin, osteoprotegerin, TRAP5b, bone-specific alkaline phosphatase and c-terminal FGF23 levels were all elevated. The most frequently recorded therapeutic procedures in dialysis CUA patients were as follows: wound debridement (29% of cases), stopping VKA (25%), lowering calcium supply (24%), sodium thiosulphate (22%), application of vitamin K (18%), increase of dialysis duration/frequency (17%) and stoping active vitamin D (16%). Conclusions. Approximately 50% of CUA patients used VKA. Our data suggest that uncontrolled hyperparathyroidism is not the key determinant of calciphylaxis. Therapeutic strategies were heterogeneous. The experience of the German registry will help substantially to initiate a large-scale multinational CUA registry.

Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover, and it plays a role in cardiovascular calcification processes. Previous findings indicate that sclerostin regulation is disturbed in chronic kidney disease (CKD). The aim of this study was to assess the association of circulating sclerostin levels with mortality in dialysis patients. From a prospective cohort study of incident dialysis patients in the Netherlands, all patients with measured circulating sclerostin at 3 months after the start of dialysis (baseline) were included in the present analysis: n = 673, age 63 ± 14 years, mean serum sclerostin (ELISA) 1.24 ± 0.57 ng/mL. By Cox regression analyses, we assessed the association of sclerostin levels with cardiovascular and non-cardiovascular mortality both in the short (18 months) and long term (4-year follow-up). Serum sclerostin levels in the entire cohort correlated with intact parathyroid hormone levels (r = −0.25, P < 0.001), age (r = 0.16, P < 0.001) and serum alkaline phosphatase (r = −0.13, P = 0.001). After adjustment for various clinical and biochemical parameters, patients in the highest sclerostin tertile had a significantly lower risk of cardiovascular death [hazard ratio 0.29, 95% confidence interval (CI) 0.13–0.62] and for all-cause mortality (0.39, 95% CI 0.22–0.68) within 18 months compared with patients of the lowest tertile. The association of sclerostin levels with outcome was less pronounced for long-term cardiovascular mortality and absent for non-cardiovascular mortality. High levels of serum sclerostin are associated with lower short-term cardiovascular mortality in dialysis patients. The exact mechanisms of this association, e.g. how sclerostin influences or reflects uraemic vascular calcification, need to be investigated in further studies.

Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare disease most frequently occurring in patients with advanced chronic kidney disease (CKD). The clinical picture is typically characterized by very painful skin lesions and ulcerations following calcification and occlusion of small cutaneous arterioles. CUA is life-threatening due to infections and concomitant cardiovascular diseases. We performed a literature search for the terms calciphylaxis and calcific uremic arteriolopathy and summarized current state-of-the-art knowledge about pathophysiology, clinical picture, course of the disease, as well as treatment options. We have filled out the literature data with our personal treatment experiences. A combination of various local and systemic risk factors are necessary to cause the development of calciphylaxis. This pathophysiological cascade is still incompletely understood. Patients with advanced CKD and dialysis patients are especially at risk to develop CUA. Regarding therapy, no randomized prospective trials are available, and treatment is rather based on pathophysiological considerations as well as on evidence derived from case reports or case series. Therapy focuses on optimized dialysis treatment, control of chronic kidney disease-mineral and bone disorder parameters, experimental anticalcification strategies and wound care. Facing the still deleterious outcome of patients with calciphylaxis, further studies on prophylaxis as well as treatment are urgently needed. Current treatment strategies may help ameliorate the course of the disease in some patients. However, it is still unclear if they are able to decrease mortality.