Systematic Review of the Impact of Erythropoiesis-stimulating Agents on Fatigue in Dialysis Patients

Background: One of the cardinal symptoms of anemia in chronic kidney disease (CKD) patients is fatigue. Recently, results from Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) raised questions about the role of erythropoiesis-stimulating agents (ESAs) in improving fatigue and the appropriate hemoglobin (Hb) target in anemic patients with CKD. These discussions should be considered with all available evidence to determine the level of benefits and risks associated with ESA therapy on fatigue among both early-stage CKD patients and end-stage renal disease patients on dialysis.

Methods: The study was a systematic review of the literature on fatigue in adults on maintenance dialysis therapy. The requirement for inclusion in the review was the measurement of fatigue before and after ESA treatment. Outcomes that were assessed were fatigue as measured by the Kidney Disease Questionnaire, the 36-item Short-Form general health survey, the Nottingham Health Profile, the Profile of Mood States or the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Several different measures of fatigue were used in the studies.

Results: Fifteen articles met the criteria for inclusion, including 10 distinct studies and one extension study. There was one placebo-controlled randomized clinical trial (RCT) and one extension, five single-arm, three high versus low, one intravenous versus subcutaneous and one switch from epoetin alfa to darbepoetin alfa. The only placebo-controlled RCT found a 22-26% improvement in fatigue. Single-arm cohort studies demonstrated a reduction in fatigue after a substantial increase in Hb. Studies with a baseline Hb <10 g/dL and partial correction to a minimum Hb ≥ 10 g/dL showed an average improvement in fatigue of 34.6%. Studies with a baseline Hb ≥ 11 g/dL and full correction to a minimum Hb ≥ 12 g/dL showed an average improvement in fatigue of 5.5%, while studies with no change in Hb (either placebo or control group) showed a decline of 0.7% in fatigue outcomes.

Conclusion: Partial correction of anemia with ESA results in improvement of fatigue among patients on dialysis, most strikingly in those patients with baseline Hb levels <10 g/dL.