Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients

Nephrol Dial Transplant. 2007 Mar;22(3):794-800. doi: 10.1093/ndt/gfl716. Epub 2007 Jan 8.


Background: The required erythropoiesis-stimulating agent (ESA) dose varies when correcting anaemia in chronic kidney disease (CKD) patients. This analysis was performed to identify the prevalence of and factors associated with ESA hyporesponsiveness.

Methods: This analysis was a post hoc evaluation of epoetin alfa dosage requirements in a subgroup of patients from the Effect of early Correction of Anemia on the Progression of CKD study. The patients in this subgroup were randomly assigned to the high haemoglobin target group (14-15 g/dl for men and 13-14 g/dl for women) and completed a 4-month haemoglobin stabilization phase with complete epoetin dosage data. The relationship of demographics, disease characteristics and laboratory measures with epoetin dosage were evaluated using Pearson's correlation, association measures and analysis of covariance (ANCOVA) models.

Results: Of the 93 patients evaluated in this subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100 IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the observed variability in epoetin dosage at completion of the stabilization phase could be accounted for by diabetes as the primary cause of kidney disease, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin, geographical region, serum iron and body mass index (BMI). Unidentified patient characteristics accounted for an additional 16% of the dosage variance.

Conclusions: Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes as the primary cause of kidney disease are associated with increased epoetin requirements when normalizing haemoglobin in anaemic CKD patients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology
  • Australia / epidemiology
  • Canada / epidemiology
  • Dose-Response Relationship, Drug
  • Epoetin Alfa
  • Erythropoietin / administration & dosage*
  • Erythropoietin / therapeutic use
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Hematinics / administration & dosage*
  • Hematinics / therapeutic use
  • Hemoglobins / drug effects
  • Hemoglobins / metabolism
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Treatment Outcome


  • Hematinics
  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • Epoetin Alfa