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Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis

  • Authors:
    • Maria Divani
    • Aikaterini Katsanaki
    • Maria Tziastoudi
    • Panagiota Makri
    • Christina Poulianiti
    • Evangelos Lykotsetas
    • Andriani Balatsouka
    • Ioannis Stefanidis
    • Theodoros Eleftheriadis
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
    Copyright: © Divani et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 43
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    Published online on: March 27, 2026
       https://doi.org/10.3892/wasj.2026.458
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Abstract

Fetuin‑A and matrix Gla protein (MGP) protect against vascular calcification. It has been suggested that low fetuin‑A levels or high levels of inactivated, dephosphorylated, uncarboxylated MGP (dp‑ucMGP) may be associated with poor cardiovascular outcomes. The present study evaluated the potential of fetuin‑A and dp‑ucMGP levels as markers of coronary heart disease (CHD) in patients undergoing hemodialysis (HD). A total of 126 patients undergoing HD (40 patients with established CHD) and 24 healthy subjects were enrolled in the study. Serum fetuin‑A and dp‑ucMGP levels were measured using ELISA. In the patients undergoing HD, fetuin‑A levels were significantly lower, whereas dp‑ucMGP levels were significantly higher than in the healthy subjects. In patients undergoing HD, fetuin‑A levels did not differ between those with or without CHD, diabetes mellitus, a C‑reactive protein (CRP) level >1 mg/dl, or heart failure. Dephosphorylated, uncarboxylated MGP was lower in patients with CHD, diabetes mellitus, a CRP level >1 mg/dl and heart failure with a reduced ejection fraction. Dephosphorylated, uncarboxylated MGP levels were shown to perform moderately well as an indicator of CHD‑free patients (area under the curve, 0.659). An increase in dp‑ucMGP by 1 ng/ml was found to decrease the risk of CHD by 23.4%. On the whole, the present study demonstrates that, in patients with HD, fetuin‑A levels are not associated with CHD. Conversely, elevated dp‑ucMGP levels indicate CHD‑free patients, although its accuracy is moderate.
View Figures

Figure 1

Comparison of serum fetuin-A and
dp-ucMGP levels between healthy individuals and patients undergoing
HD. (A) Serum fetuin-A levels were significantly lower in patients
undergoing HD compared to healthy subjects. (B) Conversely,
dp-ucMGP levels were significantly higher in patients undergoing HD
compared to healthy subjects. The line inside the box indicates the
median. The box represents the IQR, and the whiskers extend to 1.5
x IQR above and below the upper and lower quartiles, respectively.
Points outside the whiskers are outliers. *P<0.05,
vs. healthy subjects. dp-ucMGP, uncarboxylated matrix Gla protein;
HD, hemodialysis; IQR, interquartile range.

Figure 2

Serum fetuin-A levels in patients
undergoing HD with or without CHD. (A) Serum fetuin-A levels did
not differ significantly between patients undergoing HD with or
without CHD. (B) ROC curve analysis revealed an area under the
curve of 0.499 (P>0.05). HD, hemodialysis; CHD, coronary heart
disease.

Figure 3

Scatterplots of statistically
significant correlations between fetuin-A and the evaluated
factors. Serum fetuin-A levels correlated significantly with (A)
dp-ucMGP (Rho=0.311, P<0.001), (B) phosphorus (Rho=0.184,
P=0.042), (C) white blood cell count (Rho=0.280, P=0.002), and (D)
neutrophils (Rho=0.226, P=0.012). dp-ucMGP, uncarboxylated matrix
Gla protein.

Figure 4

Serum dp-ucMGP levels in patients
undergoing HD with or without CHD. (A) Serum dp-ucMGP levels were
significantly lower in patients undergoing HD with CHD compared to
those without CHD. *P<0.05, vs. those with no CHD.
(B) dp-ucMGP levels can identify patients who are free of CHD,
although its accuracy is moderate, as indicated by an area under
the curve of 0.659 (P<0.05) in ROC curve analysis. dp-ucMGP,
uncarboxylated matrix Gla protein; HD, hemodialysis; CHD, coronary
heart disease.

Figure 5

Scatterplots of statistically
significant correlations between dp-ucMGP and the evaluated
factors. Serum dp-ucMGP levels significantly correlated with (A)
age (Rho=-0.302, P<0.001), (B) body mass index (Rho=0.230,
P=0.010), (C) creatinine (Rho=0.187, P=0.037), (D) calcium
(Rho=0.398, P<0.001), (E) parathyroid hormone (Rho=0.192,
P=0.031), and (F) fetuin-A (Rho=0.311, P<0.001). dp-ucMGP,
uncarboxylated matrix Gla protein.
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Copy and paste a formatted citation
Spandidos Publications style
Divani M, Katsanaki A, Tziastoudi M, Makri P, Poulianiti C, Lykotsetas E, Balatsouka A, Stefanidis I and Eleftheriadis T: Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis. World Acad Sci J 8: 43, 2026.
APA
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E. ... Eleftheriadis, T. (2026). Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis. World Academy of Sciences Journal, 8, 43. https://doi.org/10.3892/wasj.2026.458
MLA
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E., Balatsouka, A., Stefanidis, I., Eleftheriadis, T."Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis". World Academy of Sciences Journal 8.3 (2026): 43.
Chicago
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E., Balatsouka, A., Stefanidis, I., Eleftheriadis, T."Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis". World Academy of Sciences Journal 8, no. 3 (2026): 43. https://doi.org/10.3892/wasj.2026.458
Copy and paste a formatted citation
x
Spandidos Publications style
Divani M, Katsanaki A, Tziastoudi M, Makri P, Poulianiti C, Lykotsetas E, Balatsouka A, Stefanidis I and Eleftheriadis T: Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis. World Acad Sci J 8: 43, 2026.
APA
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E. ... Eleftheriadis, T. (2026). Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis. World Academy of Sciences Journal, 8, 43. https://doi.org/10.3892/wasj.2026.458
MLA
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E., Balatsouka, A., Stefanidis, I., Eleftheriadis, T."Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis". World Academy of Sciences Journal 8.3 (2026): 43.
Chicago
Divani, M., Katsanaki, A., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E., Balatsouka, A., Stefanidis, I., Eleftheriadis, T."Fetuin‑A and dephosphorylated uncarboxylated matrix Gla protein levels in patients with established coronary heart disease undergoing hemodialysis". World Academy of Sciences Journal 8, no. 3 (2026): 43. https://doi.org/10.3892/wasj.2026.458
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