How is ESA resistance defined in patients with anemia of chronic disease and renal failure, and what are the common causes of resistance?

Updated: Apr 13, 2020
  • Author: Gates B Colbert, MD, FASN; Chief Editor: Emmanuel C Besa, MD  more...
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The working definition of ESA resistance is the requirement for greater than 150 units/kg of ESA at least 3 times per week or the sudden response refractoriness to a previous stable maintenance dose, such that hemoglobin levels fall below target levels.

The most common cause of ESA resistance is iron deficiency. Therefore, it is imperative that iron stores are adequate during ESA treatment. The second most common cause of ESA resistance is a chronic infection/inflammatory state, and such resistance is attributed to inflammatory cytokines (eg, IL-1).

Other less common causes of ESA resistance include hyperparathyroidism (the mechanism appears to be related to bone marrow fibrosis), as well as severe malnutrition.

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