Abstract

The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients. We evaluated the effect of a medium cut-off (MCO) dialyzer on ESA resistance in maintenance HD patients. Forty-nine patients who underwent high-flux HD were randomly allocated to the MCO or high-flux group. The primary outcome was the changes of erythropoietin resistance index (ERI; U/kg/wk/g/dL) between baseline and 12 weeks. The MCO group showed significant decrease in the ESA dose, weight-adjusted ESA dose, and ERI compared to the high-flux group at 12 weeks (p < 0.05). The generalized estimating equation models revealed significant interactions between groups and time for the ESA dose, weight-adjusted ESA dose, and ERI (p < 0.05). Serum iron and transferrin saturation were higher in the MCO group at 12 weeks (p < 0.05). The MCO group showed a greater reduction in TNF-α and lower serum TNF-α level at 12 weeks compared to the high-flux group (p < 0.05), whereas no differences were found in the reduction ratio of hepcidin and serum levels of erythropoietin, erythroferrone, soluble transferrin receptor and hepcidin between groups. HD with MCO dialyzer improves ESA resistance over time compared to high-flux HD in maintenance HD patients. The MCO dialyzer provides superior removal of the inflammatory cytokine and thus improves iron metabolism in a hepcidin-independent manner.

Highlights

  • The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients

  • The present study showed that HD with medium cut-off (MCO) dialyzer reduced ESA resistance compared to high-flux HD

  • The MCO dialyzer had advantages of better removal of TNF-α. This suggests that HD using MCO dialyzer causes reduced inflammation that may improve the iron metabolism and ESA response

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Summary

Introduction

The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients. The MCO group showed significant decrease in the ESA dose, weight-adjusted ESA dose, and ERI compared to the high-flux group at 12 weeks (p < 0.05). HD with MCO dialyzer improves ESA resistance over time compared to high-flux HD in maintenance HD patients. Uremic toxins and associated chronic inflammation are known to affect iron metabolism in ESRD patients and interferes with the response to E­ SA9–11. Previous studies have reported that OL-HDF clears uremic toxins of middle molecular weight (MW), improving the ESA r­ esistance[16,17,18]. Introduced medium cut-off (MCO) dialyzers have uniformly distributed larger pores and a better capacity to remove middle molecules and inflammatory cytokines than high-flux dialyzers or even OL-HDF19,20. This study aimed to evaluate whether HD with MCO dialyzer can improve the ESA resistance in chronic HD patients

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