For patients with chronic kidney disease (CKD) receiving erythropoiesis-stimulating agents (ESAs), achieving hemoglobin (Hb) levels higher than guideline-recommended target range is associated with a small but potentially clinically significant improvement in fatigue, although not in the ability to perform usual daily work or other activities.

In a systematic review and meta-analysis of 15 randomized trials and 5 observational studies, investigators compared physical component scores from patients with CKD achieving a standard (10-11.5 g/dL) or higher (11.7–13.5 g/dL) Hb target with ESA therapy. Fatigue, physical role, and physical function — measured via the Kidney Disease Questionnaire (KDQ) and the 36-Item Short Form Survey (SF-36) vitality subscale — were associated with standard mean differences of 0.16, 0.09, and 0.08, respectively, according to results published in BMC Nephrology. Subgroup analyses found a greater effect size with higher achieved Hb: 0.21 for more than 13 g/dL vs 0.09 for 11.5 to 13 g/dL. Analyses of older and long-term diabetic patients yielded lower effect sizes.

Murilo Guedes, MD, of Pontifical Catholic University of Paraná in Paraná, Brazil, and colleagues observed that “achieved hemoglobin higher than currently recommended targets may be associated with relatively modest improvement in fatigue.” Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs, they added.

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The investigators urged caution in the interpretation of these results. ESA therapy has been associated with cardiovascular and other adverse events at higher Hb target ranges. Additional research is needed to assess the relative risks and benefits of this practice.


Guedes M, Guetter CR, Erbano LHO, et al. Physical health-related quality of life at higher achieved hemoglobin levels among chronic kidney disease patients: a systematic review and meta-analysis [published online July 8, 2020]. BMC Nephrology 21:259. doi: 10.1186/s12882-020-01912-8