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Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease

Jeffrey S Berns, MD
Section Editor
Thomas A Golper, MD
Deputy Editor
Alice M Sheridan, MD


Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia associated with chronic kidney disease (CKD). ESA resistance, or hyporesponsiveness, is a term used to describe patients who do not achieve the desired hemoglobin (Hb) concentration despite higher than usual doses of ESAs or who require increasingly higher ESA doses to maintain an Hb concentration [1].

This topic reviews ESA resistance in CKD patients. Recommendations for dosing and administration of ESAs in CKD and dialysis patients are discussed elsewhere. (See "Treatment of anemia in nondialysis chronic kidney disease" and "Treatment of anemia in hemodialysis patients" and "Treatment of anemia in peritoneal dialysis patients".)


As noted above, ESA resistance is a term used to describe patients who do not achieve the desired hemoglobin (Hb) concentration despite higher than usual doses of ESAs or who require increasingly higher ESA doses to maintain a target Hb concentration [1]. ESA resistance is generally relative rather than complete. ESA resistance is also referred to as hyporesponsiveness.

Criteria for ESA resistance are not well defined. We use the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria of inability to achieve or maintain a desired Hb concentration using a maximum dose of 450 units/kg per week intravenous erythropoietin or 300 units/kg per week subcutaneous erythropoietin [2]. Criteria for other ESAs, such as darbepoetin and methoxy polyethylene glycol-epoetin beta, have not been defined, since precise dose conversions are not known. Package inserts suggest that 45,000 units/week of epoetin corresponds roughly to 100 mcg/week of darbepoetin.

Other criteria have been suggested by European Best Practice Guidelines and Kidney Disease: Improving Global Outcomes (KDIGO) [3,4]:

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Literature review current through: Dec 2017. | This topic last updated: Jan 13, 2017.
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