The impact of hyporesponsiveness to erythropoietin-stimulating agents on time-dependent mortality risk among CKD stage 5D patients: A single-center cohort study

Background: Hyporesponsiveness to a large dose of erythropoietin- stimulating agents (ESA) could increase mortality risk among chronic kidney disease patients. This study aimed to assess a safe dose of ESA and the impact of hyporesponsiveness to ESA on mortality risk among hemodialyzed patients. Methods: Patients on hemodialysis were enrolled in this cohort study. The first year was used to assess the longitudinal dialysis status of patients; the subsequent 2 years were used to assess the time-dependent risk of mortality. Results: Of the 349 subjects enrolled, 40 died within 2 years. When subjects were stratified by epoetin dose and hemoglobin level into four groups, those who had low hemoglobin despite a high dose of epoetin were associated with the highest risk of mortality among the four groups (adjusted hazard ratio 2.73; 95 % confidence interval 1.20-6.24). These highest-risk subjects had lower serum albumin and higher serum ferritin than any of the other subjects. The impact of serum albumin and serum ferritin on mortality risk in an unadjusted Cox proportional hazards model was attenuated in an adjusted model which included factors of low hemoglobin and higher ESA. A dose of epoetin up to 9000 U/week had no impact on mortality risk as long as hemoglobin levels stayed above 10 g/dL. Conclusions: Hyporesponsiveness to ESA was associated with an increased risk of mortality. There was no sign of increased mortality risk associated with epoetin itself up to a total dose of 9000 U/week.