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Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events

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Abstract

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1–5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32–42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

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Acknowledgments

We thank the patients and personnel involved in the creation of this patient material. The authors would like to express their sincere appreciation to FAVOR (FMF Arthritis Vasculitis and Orphan Diseases Research/www.favor.org.tr) web registries at Gulhane Medical Academy, Institute of Health Sciences for their supports in epidemiological and statistical advisory and invaluable guidance for the preparation of the manuscript. Part of this study was performed by Grant Nos. 1640/01.02.2013 and IDEI-PCE 2011, PN-II-ID-PCE-2011-3-0637 from the University of Medicine and Pharmacy, Iasi.

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Authors and Affiliations

  1. Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey

    Mahmut Ilker Yilmaz, Hilmi Umut Unal, Murat Karaman, Mustafa Gezer, Ali Kilinc, Tayfun Eyileten, Abdulgaffar Vural & Yusuf Oguz

  2. Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, ‘Grigore T. Popa’ University of Medicine, Iasi, Romania

    Dimitrie Siriopol & Adrian Covic

  3. Department of Radiology, Gülhane School of Medicine, Ankara, Turkey

    Mutlu Saglam

  4. Department of Biochemistry, Gülhane School of Medicine, Ankara, Turkey

    Ahmet Kerem Guler & İbrahim Aydin

  5. Nephrology and Hypertension Department, IIS-Fundacion Jimenez Diaz and School of Medicine, Madrid, Spain

    Alberto Ortiz

  6. Division of Nephrology, Department of Medicine, Koc University School of Medicine, Topkapi, 03490, Istanbul, Turkey

    Mehmet Kanbay

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  1. Mahmut Ilker Yilmaz
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Correspondence to Mehmet Kanbay.

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Conflict of Interest

Mahmut Ilker Yilmaz, Dimitrie Siriopol, Mutlu Saglam, Hilmi Umut Unal, Murat Karaman, Mustafa Gezer, Ali Kilinc, Tayfun Eyileten, Ahmet Kerem Guler, İbrahim Aydin, Abdulgaffar Vural, Yusuf Oguz, Adrian Covic, Alberto Ortiz, and Mehmet Kanbay have no conflict of interest.

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Local ethical committee approved the study protocol and all patients were included in the study after signing informed consent forms.

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Yilmaz, M.I., Siriopol, D., Saglam, M. et al. Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events. Calcif Tissue Int 99, 121–130 (2016). https://doi.org/10.1007/s00223-016-0136-4

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