Interaction between mast cell and eosinophil activation in renal anemia among hemodialysis patients

The bone marrow immune microenvironment plays a poorly understood role in renal anemia. This study aimed to investigate the independent and combined effects of mast cell activation (basal serum tryptase) and eosinophil activation (eosinophil cationic protein, ECP) on erythropoiesis in hemodialysis patients. In this cross-sectional study, 99 maintenance hemodialysis patients were stratified into four distinct phenotypes based on standard cut-off for basal tryptase and ECP: Dual Negative, Isolated Tryptase, Isolated ECP, and Dual Positive. We analyzed clinical characteristics, hematological parameters including red cell distribution width (RDW-SD), and total IgE levels to control for atopic status. Hemoglobin levels varied significantly across the phenotypes ( p = 0.004). The Isolated Tryptase group exhibited the lowest median hemoglobin [9.10 (8.75–10.20) g/dL] and the highest RDW-SD (54.00 fL), suggesting ineffective erythropoiesis. Conversely, patients in the Dual Positive group had significantly higher hemoglobin levels [10.90 (9.80–11.83) g/dL; p = 0.018 vs. Isolated Tryptase]. In multivariable linear regression, ECP showed the strongest positive association with hemoglobin, although the relationship did not reach conventional statistical significance ( p = 0.058), independent of systemic inflammation (CRP), iron status, and total IgE. Furthermore, the positive correlation between ECP and hemoglobin remained significant in the non-atopic subgroup (IgE < 100 IU/mL; rho = 0.314, p = 0.014), confirming that this relationship is not driven by allergy. ECP shows the strongest association with higher hemoglobin levels among the biomarkers tested in hemodialysis patients, an association that persists after adjustment for serum iron and is unrelated to atopic status. Conversely, isolated tryptase elevation is associated with lower hemoglobin and greater erythropoietic stress. These findings suggest that eosinophil–mast cell interactions may represent a previously underrecognized immunological pathway involved in renal anemia.