Sclerostin as a new key player in arteriovenous fistula calcification

Herz. 2015 Apr;40(2):289-97. doi: 10.1007/s00059-013-3992-y. Epub 2013 Oct 19.

Abstract

Background: The osteocyte-derived sclerostin has been shown to play a key inhibitor role in determining the normal extent of bone formation, and it consequently protects against the deleterious effects of uncontrolled bone growth. Sclerostin has been demonstrated to be upregulated during vascular smooth muscle cell calcification in vitro and has recently been identified in the human aorta at the protein level. Whether the effects of sclerostin on bone turnover and its vascular expression also translate into clinically significant changes in arteriovenous fistula patency is unknown.

Patients and methods: The primary outcome was loss of unassisted arteriovenous fistula patency, defined as arteriovenous fistula thrombosis or need for intervention. In this prospective cohort study, 350 prevalent hemodialysis patients were followed up for 12 months. Serum sclerostin levels were measured and arteriovenous fistula calcification was detected using a 64-detector computerized tomographic scanner.

Results: Patients with calcified arteriovenous fistula had higher serum sclerostin levels than patients without. Overall, 26 % of the patients reached the outcome during the follow-up. The 12-month arteriovenous fistula survival was reduced in patients with calcified arteriovenous fistulas. Patients with serum sclerostin levels above median levels at the start of the observation period had a worse arteriovenous fistula survival. Multivariable-adjusted Cox regression analyses revealed that only presence of arteriovenous fistula calcification and serum C-reactive protein level independently predicted loss of unassisted arteriovenous fistula patency.

Conclusion: Our study suggests that the detection of arteriovenous fistula calcification and serum C-reactive protein levels might be useful for identifying patients at an increased risk for loss of unassisted arteriovenous fistula patency.

Publication types

  • Observational Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Anastomosis, Surgical / adverse effects
  • Arteriovenous Anastomosis / surgery*
  • Biomarkers / blood
  • Bone Morphogenetic Proteins / blood*
  • Calcinosis / blood*
  • Calcinosis / diagnosis
  • Calcinosis / etiology*
  • Female
  • Genetic Markers
  • Graft Rejection / blood*
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology*
  • Hemofiltration / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Reproducibility of Results
  • Risk Assessment
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human