Hepatokine FGL1 and hepcidin in anemia of chronic kidney disease: A cross sectional study

Anemia in chronic kidney disease (CKD) results from complex interactions involving inflammation, erythropoietin (EPO) deficiency, and iron imbalance. Although hepcidin, erythroferrone (ERFE), and IL-6 are established regulators of iron metabolism, the specific role of the hepatokine fibrinogen-like protein 1 (FGL1) in CKD-related iron homeostasis remains undefined. This study investigated the regulatory role of FGL1 on hepcidin expression and its association with ERFE and IL-6 in dialysis-dependent CKD patients. In this comparative cross-sectional study, hematological and biochemical parameters were assessed in CKD patients on maintenance hemodialysis (n=42) and matched healthy controls (n=42). Serum FGL1, ERFE, hepcidin, and IL-6 levels were quantified using the enzyme-linked immunosorbent assay (ELISA). Correlation and regression analyses were performed to examine associations among these markers and with clinical variables. CKD patients had low hemoglobin, red cell count, red cell indices, and serum iron as compared with the control group. FGL1 levels were significantly reduced in CKD patients compared to controls (25.46 ± 9.65 vs. 46.47 ± 31.52, p = 0.02). Hepcidin levels were elevated (CKD 3639.19 ± 635.65 vs. Controls 502 ± 220.63), consistent with inflammation-driven iron sequestration. ERFE and IL-6 levels showed no significant differences. A moderate positive correlation was observed between FGL1 and both hepcidin and ERFE. No significant associations were noted with conventional hematological markers. Regression models identified no strong predictors for clinical variables, including erythropoiesis-stimulating agent (ESA) use. Reduced FGL1 levels in CKD patients may reflect impaired hepatic regulation of iron metabolism via the BMP6-hepcidin axis. Despite elevated hepcidin, ERFE and IL-6 levels were not significantly different, with only moderate correlations. These findings suggest a potential role for FGL1 in CKD-associated anemia and highlight the need for further mechanistic studies to clarify its clinical significance.