BACKGROUND The impact of anemia treatment with erythropoietin stimulating agents (ESA) on health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients is controversial, particularly regarding optimal hemoglobin (Hb) target ranges .
METHODS We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCT) with ESA to estimate the effect of different achieved Hb values on physical HRQOL and functionality . We searched PubMed, EMBASE, CENTRAL, PEDro, PsycINFO and Web of Science databases, until May 2020 . Two authors independently extracted data from studies . We included observational and RCTs that enrolled CKD patients undergoing anemia treatment with ESA with different achieved Hb levels among groups . We excluded studies with achieved Hb <9 g/dL . For the meta-analysis, we included RCTs with control groups achieving Hb 10-11.5 g/dL and active groups with Hb> 11.5 g/dL . We analyzed the standardized mean difference (SMD) between groups for physical HRQOL .
RESULTS Among 8496 studies, fifteen RCTs and five observational studies were included for the systematic review . We performed the meta-analysis in a subset of eleven eligible RCTs . For physical role and physical function, SMDs were 0.0875 [95% CI: - 0.0025 - 0.178] and 0.08 [95% CI: - 0.03 - 0.19], respectively . For fatigue, SMD was 0.16 [95% CI : 0.09-0.24]. Subgroup analysis showed that trials with greater achieved Hb had greater pooled effects sizes - 0.21 [95% CI : 0.07-0.36] for Hb> 13 g/dL vs. 0.09 [95% CI : 0.02-0.16] for Hb 11.5-13 g/dL . Proportion of older and long-term diabetic patients across studies were associated with lower effect sizes .
CONCLUSION Achieved hemoglobin higher than currently recommended targets may be associated with small but potentially clinically significant improvement in fatigue, but not in physical role or physical function . Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs.