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. 2025 Jul 30:16:1503940.
doi: 10.3389/fendo.2025.1503940. eCollection 2025.

Predictive value of ferritin heavy chains in the development of coronary artery calcification in patients on maintenance hemodialysis: a prospective cohort study

Sipei Chen #  1 , Yu Tang #  1 , Yangmei Pu #  2 , Xiaoqiang Xia  3 , Yi Li  1 , Yang Zou  1
Affiliations

Predictive value of ferritin heavy chains in the development of coronary artery calcification in patients on maintenance hemodialysis: a prospective cohort study

Sipei Chen et al. Front Endocrinol (Lausanne). .

Abstract

Background: Vascular calcification (VC) is a well-established risk factor for cardiovascular disease (CVD) and mortality in patients on maintenance hemodialysis (MHD). These patients frequently present with hyperphosphatemia as well as disorders of iron metabolism. This study aims to explore the role of ferritin heavy chain (FTH) in the development and progression of coronary artery calcification (CAC) in patients on MHD and assess its predictive value.

Methods: Using a bioinformatics approach, we analyzed datasets related to VC. In our prospective study, we evaluated the Coronary Artery Calcification Score (CACS) alongside clinical markers, including serum FTH, serum ferritin, and transferrin saturation (TSAT), in patients on MHD at baseline and after a 1-year follow-up.

Results: Fth1 was identified as a differentially expressed gene significantly upregulated in the aorta of both ApoE-/- mice (atherosclerotic calcification model) and chronic kidney disease (CKD) mice (medial calcification model). Among patients on MHD, 85.71% exhibited CAC, with 49.09% showing progression. Patients with CAC tended to be older and have a higher body mass index (BMI). Notably, serum FTH and phosphorus (P) levels were significantly elevated in those with progressive CAC. Elevated serum FTH and high serum P were both independent risk factors for CAC progression and showed predictive value.

Conclusion: Elevated serum FTH and high serum phosphorus are clinically significant predictors of VC progression in patients on MHD.

Keywords: ferritin heavy chain; maintenance hemodialysis; predictive value; risk factors; vascular calcification.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the patient screening workflow.
Figure 2
Figure 2
RNA-Seq analysis of aortas from CKD and ApoE-/- calcified mice. DEGs were analyzed using DESeq2 (|log2 fold change| > 1, P < 0.05). (A) Volcano plot of DEGs (Ctrl vs. CKD + ApoE-/-), with upregulated (red) and downregulated (green) genes highlighted. (B) Venn diagram of DEGs overlapping in Ctrl vs. CKD (green) and Ctrl vs. ApoE-/- (blue). (C) PPI network of Fth1 and its interactors (Ftl1, Ftl1-ps1, Ncoa4, Tfrc). (D, E) Heatmap of Fth1 and associated proteins, along with Fth1 expression levels across groups (histogram). **Statistical significance vs. Ctrl: **P < 0.01, ***P < 0.001. Ctrl, control; CKD, Chronic kidney disease; ApoE-/-, Apolipoprotein E knockout mice; DEGs, Differentially Expressed Genes; PPI, Protein-Protein Interaction.
Figure 3
Figure 3
Prediction of CAC progression by serum FTH and P. (A) ROC curve for serum FTH. (B) ROC curve for serum P. FTH, Ferritin heavy chain; P, phosphorus.
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