Chi-yuan Hsu, MD, MSc
What are the benefits and harms of erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease (CKD) and anemia?
Included studies compared ESAs (erythropoietin-alfa or -beta, darbepoetin, or continuous erythropoietin receptor activator) with placebo, no treatment, or different ESA doses to achieve a higher versus a lower hemoglobin target in patients with CKD and anemia and were ≥ 3 months in duration. Reported outcomes included all-cause mortality, stroke, hypertension, serious cardiovascular (CV) events, vascular access thrombosis, end-stage kidney disease needing renal replacement therapy, blood transfusions, and intravenous (IV) iron therapy.
MEDLINE and EMBASE/Excerpta Medica (to Nov 2009), and Cochrane Renal Group trial register and Cochrane Central Register of Controlled Trials (to Mar 2010) were searched for randomized controlled trials (RCTs). 27 RCTs (n = 10 452) met the selection criteria, with median achieved hemoglobin levels of 101 g/L in the low-target group (interquartile range [IQR] 92 to 110) and 130 g/L in the high-target group (IQR 120 to 140).
Meta-analysis showed that ESAs targeted to higher compared with lower hemoglobin levels reduced need for blood transfusions (relative risk [RR] reduction 39%, 95% CI 23 to 51) but increased risk for hypertension, vascular access thrombosis, and stroke (Table), and need for IV iron therapy (RR increase 57%, CI 13 to 120). Groups did not differ for mortality, serious CV events, or need for renal replacement therapy in end-stage disease (Table).
Erythropoiesis-stimulating agents targeted to higher hemoglobin levels reduce need for blood transfusions but increase adverse outcomes in patients with chronic kidney disease and anemia.
Treatment targeted to higher hemoglobin levels (ESAs) vs lower hemoglobin levels (placebo, no treatment, or different ESA doses) in patients with chronic kidney disease and anemia*
*CV = cardiovascular; ESA = erythropoiesis-stimulating agent; RRT = renal replacement therapy; other abbreviations defined in Glossary. Weighted event rates, RRI, NNH, and CI calculated from data in article using a random-effects model.
Hsu C. Review: Erythropoiesis-stimulating agents targeted to higher hemoglobin levels increase risk for adverse outcomes in CKD. Ann Intern Med. 2010;153:JC5–3. doi: 10.7326/0003-4819-153-10-201011160-02003
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Published: Ann Intern Med. 2010;153(10):JC5-3.
Cardiology, Chronic Kidney Disease, Coronary Risk Factors, Hematology/Oncology, Hypertension.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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