Improvements in Fatigue at Higher Achieved Hemoglobin Levels Among Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

Abstract

Background: The impact 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 Hb ranges on physical HRQOL and functionality. We searched PubMed, EMBASE, CENTRAL, PEDro, PsycINFO and Web of Science databases, until May 2019Two 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 8,171 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 [CI:-0.0025 – 0.178] and 0.08 [CI: -0.03 – 0.19], respectively. For fatigue, SMD was 0.16 [0.09 - 0.24]. Subgroup analysis showed that trials with greater achieved Hb had greater pooled effects sizes — 0.21 [0.07 - 0.36] for Hb > 13 g/dL vs. 0.09 [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 is associated with small but clinically significant improvement in fatigue. Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs.