The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis

Ann Intern Med. 2016 Apr 5;164(7):472-8. doi: 10.7326/M15-1839. Epub 2016 Feb 16.


Background: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear.

Purpose: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis.

Data sources: Searches of PubMed, EMBASE, the Cochrane Library, and from inception to 1 November 2015, supplemented with manual screening.

Study selection: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics.

Data extraction: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools.

Data synthesis: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients.

Limitation: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias.

Conclusion: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD.

Primary funding source: KRESCENT and Manitoba Health Research Council Establishment.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology
  • Hematinics / therapeutic use*
  • Hemoglobins / metabolism
  • Humans
  • Quality of Life*
  • Renal Dialysis
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / therapy


  • Hematinics
  • Hemoglobins