title: The impact of hyporesponsiveness to erythropoietin-stimulating agents on time-dependent mortality risk among CKD stage 5D patients: a single-center cohort study.
abstract: 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.
authors: Department of Nephrology, Shuwa General Hospital, 1200 Yahara-Shinden Kasukabe-shi, Saitama 344-0035, Japan. junichi_ishigami@hotmail.com
authors: Junichi
authors: J
authors: Ishigami
authors: Tsuyoshi
authors: T
authors: Onishi
authors: Satomi
authors: S
authors: Shikuma
authors: Wataru
authors: W
authors: Akita
authors: Yoshihiro
authors: Y
authors: Mori
authors: Tomoki
authors: T
authors: Asai
authors: Michio
authors: M
authors: Kuwahara
authors: Sei
authors: S
authors: Sasaki
authors: Yusuke
authors: Y
authors: Tsukamoto
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C422455:ALB protein, human; D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D012709:Serum Albumin; C103998:epoetin beta; D004921:Erythropoietin; D005293:Ferritins; D000075462:Serum Albumin, Human