Associations between erythropoietin resistance and iron metabolism markers in patients undergoing extended-hours and conventional hemodialysis

Abstract Background Extended-hours hemodialysis, defined as ≥6 h/session, three or four times per week, has been associated with lower erythropoietin resistance index (ERI), although the biological mechanisms remain unclear. We aimed to compare the associations between ERI and iron metabolism markers in patients undergoing extended-hours versus conventional hemodialysis. Methods We included patients who received either extended-hours or conventional hemodialysis between January and March 2020. The ERI was calculated by dividing the weekly erythropoiesis-stimulating agent (ESA) dose, expressed as epoetin equivalents divided by body weight and hemoglobin level. Linear and non-linear associations were evaluated using multivariable linear regression and restricted cubic spline (RCS) analyses. Results We analyzed 366 patients (178 receiving extended-hours hemodialysis and 188 receiving conventional hemodialysis). Hemoglobin levels were 10.9 and 11.2 g/dL, median ferritin levels were 34.8 and 63.6 ng/mL, and median transferrin saturation (TSAT) values were 16.9% and 20.5%, respectively. Extended-hours hemodialysis was associated with a lower ERI after multivariable adjustment (coefficient, −4.49 IU/kg/week per g/dL; 95% confidence interval, −6.76 to −2.22). In the RCS analysis, ERI increased with decreasing ferritin levels in the conventional hemodialysis group, whereas no increase was observed at lower ferritin levels in the extended-hours group. A similar trend was observed with respect to TSAT. Conclusions Extended-hours hemodialysis was associated with lower ERI. Exploratory RCS analyses suggested potential modality-related differences in the relationships between ERI and ferritin or TSAT. These findings suggest that the association between iron status and ESA responsiveness may differ by dialysis modality and warrants further investigation.