Impact of Erythropoiesis-Stimulating Agents on Energy and Physical Function in Nondialysis CKD Patients With Anemia: A Systematic Review

Background: Previous analyses report the impact of erythropoiesis-stimulating agents (ESAs) on health-related quality of life across various populations. In this analysis, we review published studies and quantify the effect of ESA therapy on energy/fatigue and physical function in nondialysis patients with chronic kidney disease (CKD) related anemia. Study Design: Systematic literature search to identify articles (1980-2008) that evaluated effects of ESAs on patient-reported energy and physical function. Setting & Population: Nondialysis CKD patients with anemia enrolled in prospective trials. Selection Criteria for Studies: Prospective studies measuring energy or physical function with both baseline and follow-up measurement. Intervention: ESA treatment. Outcomes: Improvements in energy and physical function assessed using effect size, a measure of treatment responsiveness. Results: 14 studies were identified: 11 measured energy and 14 measured physical function. The 36-Item Short-Form Health Survey (SF-36) was the most common instrument used to report energy and physical function. Of 11 studies measuring energy, 2 were double-blind randomized placebo-controlled trials (RCTs), 5 were open-label RCTs, and 4 were single-arm open-label studies. Eight of 11 studies reported statistically significant improvements in energy. Effect size for energy ranged from small (0.24) to large (1.90) in ESA-treated groups and was moderate in each arm of the low-versus high-hemoglobin target RCTs. Of 14 studies measuring physical function, 2 were double-blind RCTs, 6 were open-label RCTs, and 6 were single-arm open-label studies. Ten of 14 studies reported statistically significant improvements in physical function. Effect size for physical function ranged from small (0.37) to large (2.38) in ESA-treated groups and was negligible to moderate in each arm of low-versus high-hemoglobin target studies. Limitations: Findings and conclusions were limited by the available evidence. Conclusion: RCTs and single-arm studies indicate that treatment of anemia with ESAs improves energy and physical function in nondialysis CKD patients. Am J Kidney Dis 55: 519-534. (C) 2010 by the National Kidney Foundation, Inc.