Anemia of chronic kidney disease
ICD-10 D63.1 · ICD-11 3A71.2

Managing Anemia in Chronic Kidney Disease G5 on Hemodialysis After ESA Hyporesponsiveness

This protocol applies to patients with anemia in the setting of chronic kidney disease G5 who are receiving hemodialysis and have not achieved the expected hemoglobin response with erythropoiesis-stimulating agent (ESA) therapy.

Clinical scenario

Anemia in adults with stage G5 chronic kidney disease currently receiving hemodialysis (CKD G5HD). Correctable causes of anemia have been evaluated. ESA hyporesponsiveness is present — the patient has not reached the hemoglobin target on first-line ESA therapy.

When first-line ESA therapy did not work

First-line treatment used an erythropoiesis-stimulating agent (ESA), targeting an increase in hemoglobin concentration while keeping it below 11.5 g/dl, with hemoglobin monitoring every 2–4 weeks. ESA hyporesponsiveness — failure to achieve this rise — is the condition that triggers escalation to the next treatment step described here.

Next-line approach

After correctable causes have been addressed, a trial course of a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI) may be considered. It is used alone — not in combination with an ESA. The clinical goal is a hemoglobin rise within 3–4 months, with close monitoring after initiation. The specific agent and full dosing algorithm are available in the complete protocol.

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References

DOI: 10.1016/j.kint.2025.06.006

  1. In people with anemia and CKD G5 receiving hemodialysis (CKD G5HD), we suggest initiating iron therapy if ferritin ≤500 ng/ml (≤500 μg/l) and TSAT ≤30% (2D).
  2. In people with CKD, anemia, and ESA hyporesponsiveness, if there is a desire to raise Hb to avoid transfusion or improve symptoms attributable to anemia, a trial course of HIF-PHI may be considered after discussion of potential risks and benefits (Figure 10).
  3. In people with anemia and CKD, if a decision is made to use HIF-PHIs for the treatment of ESA hyporesponsiveness, use the lowest dose that alleviates anemia-related symptoms or reduces the risk of requiring an RBC transfusion.
  4. In people with anemia and CKD, including those with ESA hyporesponsiveness, do not use ESAs and HIF-PHIs in combination.
  5. In people with anemia and CKD, discontinue HIF-PHI after 3–4 months if a desired erythropoietic response has not been achieved.
  6. In people with anemia and CKD, when administering HIF-PHIs, monitor Hb levels 2–4 weeks after initiation or dose adjustments and subsequently every 4 weeks during therapy.
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