Association of Erythropoietin Resistance with Fatigue in Hemodialysis Patients: A Cross-Sectional Study

Abstract

Background/Aims: Fatigue is a common symptom in patients receiving hemodialysis (HD) and is generally associated with anemia. However, it can be difficult to resolve, even when anemia has been treated using erythropoiesis-stimulating agents and iron replacement therapy. In the present study, we examined the associations of anemia, the erythropoietin resistance index (ERI) and iron deficiency with fatigue during HD. Methods: In this cross-sectional study, fatigue score was calculated on the basis of questionnaire responses in HD patients. Participants were divided into 3 groups according to their hemoglobin (Hb) levels (low, normal and high). Iron deficiency was assessed as a transferrin saturation (TSAT) of <20%. Results: We included 571 HD patients (men/women 368/203; mean age 62.2 ± 10.8 years). Among the 3 groups, fatigue scores increased significantly with decreasing Hb levels. HD patients with low Hb levels (<90 g/l) had significantly higher fatigue scores than those with higher Hb levels (≥120 g/l). In the multiple regression analysis, we showed that a high ERI (β = 0.208) and a low TSAT (β = -0.155), but not the Hb level, were significantly associated with increased fatigue score. Moreover, this was independent of age, gender and modifiable confounders linked to anemia. Even after restricting patients to those without iron deficiency (TSAT ≥20%), the ERI (β = 0.258) retained a significant and independent association with the fatigue score. Conclusion: Iron deficiency and a high ERI despite iron sufficiency may cause fatigue in HD patients.