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Sclerostin as a new key player in arteriovenous fistula calcification

Sclerostin als neuer Ansatz bei Kalzifizierung des arteriovenösen Shunts

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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.

Zusammenfassung

Hintergrund

Das in Osteozyten gebildete Sclerostin spielt nachgewiesenermaßen als Inhibitor eine Schlüsselrolle dabei, das normale Ausmaß der Knochenbildung festzulegen, und dient somit als Schutz vor den schädlichen Wirkungen eines unkontrollierten Knochenwachstums. Sclerostin wird, wie gezeigt wurde, während der Kalzifizierung von vaskulären glatten Muskelzellen in vitro hochreguliert und ist auf Proteinebene vor Kurzem in der menschlichen Aorta nachgewiesen worden. Ob die Wirkung von Sclerostin auf den Knochenstoffwechsel und seine Expression in Gefäßen auch von klinischer Bedeutung für Veränderungen bei der Durchgängigkeit eines arteriovenösen Shunts ist, ist nicht bekannt.

Methoden

Der primäre Endpunkt war der Verlust der Durchgängigkeit des arteriovenösen Shunts ohne weitere Maßnahmen, was als Shuntthrombose oder Notwendigkeit der Intervention definiert war. In dieser prospektiven Kohortenstudie wurden 350 Patienten mit bestehender Hämodialysetherapie 12 Monate lang nachbeobachtet. Es wurden die Sclerostinwerte im Serum bestimmt und die Kalzifizierung des arteriovenösen Shunts mit einem 64-Zeilen-Computertomographen ermittelt.

Ergebnisse

Bei Patienten mit Kalzifizierung des arteriovenösen Shunts war der Sclerostinwert im Serum höher als bei Patienten ohne Shuntkalzifizierung. Insgesamt trat der Endpunkt bei 26 % der Patienten während des Nachbeobachtungszeitraums ein. Das 12-Monats-Überleben des arteriovenösen Shunts war bei Patienten mit Shuntkalzifizierung vermindert. Bei Patienten mit Sclerostinwerten im Serum oberhalb des Durchschnittswerts zu Beginn der Beobachtungsphase war das Überleben des arteriovenösen Shunts schlechter. Die unter Berücksichtigung mehrerer Variablen durchgeführte Cox-Regressionsanalyse ergab, dass nur das Vorliegen einer Shuntkalzifizierung und der Wert für C-reaktives Protein (CRP) im Serum den Verlust der Shuntdurchgängigkeit ohne weitere Maßnahmen unabhängig vorhersagten.

Schlussfolgerungen

Der vorliegenden Studie zufolge können die Diagnosestellung einer Kalzifizierung des arteriovenösen Shunts und die Bestimmung des CRP im Serum bei der Erkennung von Patienten mit erhöhtem Risiko für den Verlust der Durchgängigkeit des Shunts ohne weitere Maßnahmen von Nutzen sein.

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Compliance with ethical guidelines

Conflict of interest. M. Balcı, A. Kırkpantur, A. Turkvatan, S. Mandıroglu, E. Ozturk, and B. Afsar state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies. Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.

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Authors and Affiliations

  1. Division of Cardiology, Yuksek Ihtisas Hospital, Ankara, Turkey

    M. Balcı

  2. Division of Nephrology, RFM Renal Treatment Services, Ragip Tuzun Caddesi No. 39 Yenimahalle, 06710, Ankara, Turkey

    A. Kırkpantur MD

  3. Division of Radiology, Yuksek Ihtisas Hospital, Ankara, Turkey

    A. Turkvatan

  4. Division of Physical Therapy and Rehabilitation, Physical Therapy and Rehabilitation Hospital, Ankara, Turkey

    S. Mandıroglu

  5. Division of Biostatistics, Hacettepe University School of Medicine, Ankara, Turkey

    E. Ozturk

  6. Division of Nephrology, Konya Numune State Hospital, Konya, Turkey

    B. Afsar

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  1. M. Balcı
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  2. A. Kırkpantur MD
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Correspondence to A. Kırkpantur MD.

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Balcı, M., Kırkpantur, A., Turkvatan, A. et al. Sclerostin as a new key player in arteriovenous fistula calcification. Herz 40, 289–297 (2015). https://doi.org/10.1007/s00059-013-3992-y

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  • DOI: https://doi.org/10.1007/s00059-013-3992-y

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