Inflammation and iron availability in erythropoiesis resistance: a longitudinal patient-month analysis in hemodialysis patients

Abstract Background Iron availability and inflammation are important factors in anemia management in hemodialysis patients; however, their longitudinal relationships with erythropoiesis resistance index (ERI), including potential temporal effects, remain incompletely understood. Methods We conducted a retrospective longitudinal study of maintenance hemodialysis patients using patient-month-level data over 12 months. Variables included hemoglobin, ESA dose, transferrin saturation (TSAT), C-reactive protein (CRP), and iron indices. ERI was used as a marker associated with ESA response. Linear mixed-effects models with patient-specific random intercepts were applied to evaluate associations with ERI, including an interaction term between TSAT and CRP and analyses incorporating lagged variables. Results A total of 57 patients contributed 684 patient-month observations. ERI was higher in patient-months characterized by low TSAT and elevated CRP. In mixed-effects models, lower TSAT was independently associated with higher ERI, whereas same-month CRP was not independently associated with ERI. The interaction term between TSAT and CRP was not statistically significant. In stratified analyses, TSAT showed an inverse association with ERI in both low- and high-CRP conditions. However, greater variability in ERI was observed in the elevated CRP group. In addition, prior-month CRP was positively associated with ERI, suggesting a delayed effect of inflammation on erythropoietic responsiveness. Conclusions Lower TSAT is associated with higher ERI in maintenance hemodialysis patients. While CRP was not associated with ERI in same-month analyses, prior-month CRP showed a significant association, suggesting a delayed effect of inflammation. These findings support a longitudinal, individualized approach to anemia management that considers both iron availability and the temporal impact of inflammation.