Brandenburg Vincent M, Kramann Rafael, Rothe Hansjörg, Kaesler Nadine, Korbiel Joanna, Specht Paula, Schmitz Sophia, Krüger Thilo, Floege Jürgen, Ketteler Markus
Department of Cardiology, University Hospital of the RWTH Aachen, Aachen, Germany.
Center for Rare Diseases, University Hospital of the RWTH Aachen (ZSEA), Aachen, Germany.
Nephrol Dial Transplant. 2017 Jan 1;32(1):126-132. doi: 10.1093/ndt/gfv438.
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.
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.
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%).
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.
钙化性尿毒症小动脉病（CUA，钙化防御）是一种主要发生于透析患者的罕见疾病，死亡率高。疼痛性皮肤溃疡和皮肤小动脉钙化是钙化防御的特征。
我们建立了一个基于互联网的观察性登记系统，允许对所有德国CUA病例进行在线报告。该登记系统记录了患者特征、生化指标和治疗方法的数据。血样存储在一个中央生物样本库中。
2006年至2015年期间，记录了253例CUA患者：中位年龄70岁[四分位间距（IQR）61 - 76岁]，60%为女性，86%（n = 207）为透析患者，这意味着德国透析患者的估计年发病率为0.04%。52%的患者在发生CUA之前使用维生素K拮抗剂（VKA）。71%的皮肤病变位于腿部或臀部区域。透析CUA患者的血清总钙中位值为2.20（IQR 2.06 - 2.37）mmol/L，磷为1.67（IQR 1.35 - 2.03）mmol/L，完整甲状旁腺激素为147（IQR 72 - 276）pg/mL，胎球蛋白-A为0.21（IQR 0.16 - 0.26）g/L（正常范围0.35 - 0.95）。硬化蛋白、骨保护素、TRAP5b、骨特异性碱性磷酸酶和C端FGF23的中位水平均升高。透析CUA患者最常记录的治疗方法如下：伤口清创（29%的病例）、停用VKA（25%）、减少钙供应（24%）、硫代硫酸钠（22%）、应用维生素K（18%）、增加透析时长/频率（17%）和停用活性维生素D（16%）。
约50%的CUA患者使用VKA。我们的数据表明，未控制的甲状旁腺功能亢进不是钙化防御的关键决定因素。治疗策略各不相同。德国登记系统的经验将极大地有助于启动一个大规模的跨国CUA登记系统。
