Systematic Review and Meta-analysis of Exercise Tolerance and Physical Functioning in Dialysis Patients Treated With Erythropoiesis-Stimulating Agents

Background

The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning.

Study Design

A systematic review and meta-analysis of exercise tolerance and physical functioning.

Setting & Participants

Adults on maintenance dialysis therapy.

Selection Criteria for Studies

Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants.

Intervention

Treatment with any ESA.

Outcomes

Exercise tolerance measured using VO_2peak (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using ≥ 1 patient- or clinician-reported outcome measure that included a physical function domain.

Results

28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO_2peak from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation.

Limitations

Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function.

Conclusions

Partial correction of anemia through ESA treatment has a consistent and positive impact on VO_2peak. ESA treatment improves patient- and clinician-assessed physical functioning.

Index Words: Chronic kidney disease, erythropoiesis-stimulating agents, epoetin alfa, exercise tolerance, quality of life