The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers

Mohamed M Nasrallah; Amal R El-Shehaby; Noha A Osman; Tarek Fayad; Amr Nassef; Mona M Salem; Usama A A Sharaf El Din

doi:10.1159/000356118

The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers

Nephron Extra. 2013 Nov 6;3(1):106-112. doi: 10.1159/000356118. eCollection 2013.

Authors

Mohamed M Nasrallah¹, Amal R El-Shehaby², Noha A Osman¹, Tarek Fayad¹, Amr Nassef³, Mona M Salem⁴, Usama A A Sharaf El Din¹

Affiliations

¹ Department of Nephrology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
² Department of Medical Biochemistry, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
³ Department of Radiology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
⁴ Department of Endocrinology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.

Abstract

Background: Fibroblast growth factor-23 (FGF-23) has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD), although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated.

Methods: We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP), endogenous soluble receptor of advanced glycation end products (esRAGE), advanced oxidation protein products (AOPP), parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI) was determined using non-contrast CT scans of the abdominal aorta.

Results: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906) and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R² = 0.7, p < 0.001). In univariate analysis, ACI correlated with hsCRP, esRAGE, FGF-23, dialysis vintage, systolic blood pressure (BP) and serum cholesterol. In multiple regression analysis not including inflammation markers, ACI was associated with FGF-23. However, inclusion of inflammation markers in another multiple regression analyses showed that ACI correlated with hsCRP, BP, dialysis vintage and esRAGE but not with FGF-23 (R² = 0.65, p < 0.001).

Conclusion: FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.

Keywords: Chronic kidney disease; Chronic kidney disease; Fibroblast growth factor-23; Inflammation markers; Uremic toxins; Vascular calcification.