Abstract: SA-PO688
The Novel Bone Alkaline Phosphatase Isoform B1x in Serum Identifies Patients with Calciphylaxis on Vitamin K Antagonist Treatment
Session Information
- Bone and Mineral Metabolism: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Haarhaus, Mathias, Karolinska Institutet, Stockholm, Sweden
- Brandenburg, Vincent, Rhein-Maas Klinikum, Würselen, Germany
- Ketteler, Markus, Klinikum Coburg GmbH, Coburg, Germany
- Kramann, Rafael, RWTH Aachen University, Aachen, Germany
- Magnusson, Per, Linköping University, Linköping, Sweden
Background
The novel bone alkaline phosphatase (BALP) isoform B1x is only detectable in serum from patients with advanced chronic kidney disease (CKD) or end-stage renal disease. B1x has been proposed as a marker for low bone turnover, furthermore, B1x activity increases in calcifying vascular smooth muscle cells. Vitamin K antagonists (VKA) prevent activation of the potent vascular calcification inhibitor matrix Gla protein. VKA is associated with an increased risk for calciphylaxis (calcific uremic arteriolopathy, CUA), a rare and often fatal complication associated with severe calcification of arterioles. The objective was to study the appearance of B1x in serum from CKD patients with CUA.
Methods
Seventeen CKD patients with CUA (15 on hemodialysis, 1 transplanted, 1 pre-dialysis) were recruited from the European Calciphylaxis Network. Serum total ALP was determined by a kinetic assay and the BALP isoforms (B/I, B1, B1x and B2) by high-performance liquid chromatography. Fetuin A, intact parathyroid hormone (iPTH), total BALP (ELISA), C-reactive protein, sclerostin, C-terminal fibroblast growth factor 23, tartrate-resistant acid phosphatase type 5b (TRAP5b), osteoprotegerin, 25-OH vitamin D, total calcium (Ca) and phosphate were also assessed.
Results
B1x was detected in 10 patients (56%). These patients were more often treated with VKA (7 VKA patients B1x positive, vs 1 VKA patient B1x negative), had a more frequent history of myocardial infarction, lower total ALP (P=0.025), lower BALP (P=0.025), lower BALP isoform B1 (P<0.001) and lower total Ca (P=0.014) in serum. There was a tendency towards lower iPTH and lower TRAP5b (P=0.055 for both).
Conclusion
Patients with B1x were more often treated with VKA. Circulating bone markers indicate an association of B1x with low bone turnover. We hypothesize that VKA induce a specific subtype of vascular calcification, which is different from non-VKA-users. Based on the BALP isoform analysis, subgroups of CUA could be identified, which might also reveal differences in terms of bone metabolism.
Funding
- Commercial Support – Amgen