The effects of hypoxia-inducible factors-1 alpha and-2 alpha and erythroferrone on hepcidin in patients with chronic kidney disease stages 3-5 and renal anemia

Objective: This study aimed to investigate the effects of hypoxia-inducible factor-1 alpha (HIF-1 alpha), hypoxia-inducible factor-2 alpha (HIF-2 alpha), and erythroferrone (ERFE) on hepcidin in patients with chronic kidney disease (CKD) stages 3-5 and renal anemia. Methods: A total of 90 patients with CKD stages 3-5 and renal anemia were selected for the study at the Nephrology Department of Fujian Provincial People's Hospital and divided into three groups, according to CKD stage, while another 30 healthy subjects who underwent a physical examination at the hospital during the same period were selected as the normal group. The serum levels of hepcidin, HIF-1 alpha, HIF-2 alpha, ERFE, and furin were measured using an avidin biotin peroxidase complex enzyme-linked immunosorbent assay to compare the differences between the groups in the related indicators. Results: (1) Serum HIF-2 alpha, HIF-1 alpha, ERFE, and furin levels increased gradually in the patients with CKD stages 3-5 (p < 0.05, p < 0.01). (2)Simple correlation analysis:Serum hepcidin was positively correlated with HIF-2 alpha, ERFE, and HIF-1 alpha in the CKD patients (p < 0.01). (3)Serum hepcidin was positively correlated with HIF-2a, HIF-1 alpha, and ERFE in the CKD patients injected with erythropoietin (EPO) (p < 0.01), while serum hepcidin was positively correlated with HIF-2 alpha and HIF-1 alpha (p < 0.01) in the patients not injected with EPO. (4)Multivariate linear regression analysis showed that HIF-1 alpha, (beta = 4.36, p < 0.01), serum ferritin(SF) (beta = 0.13, p < 0.01), and HIF-2 alpha (beta = 0.66, p < 0.01) were significantly correlated with hepcidin. Conclusion: HIF-1 alpha, HIF-2 alpha, and SF are factors which have an effect on hepcidin in patients with CKD stages 3-5 and renal anemia. The increase of HIF-1 alpha, HIF-2 alpha, and ERFE does not seem to inhibit the increase of hepcidin.