Treatment of Anemia in Chronic Kidney Disease G5 on Hemodialysis After HIF-PHI Therapy Has Not Achieved the Expected Hemoglobin Response

This protocol applies to patients with anemia and chronic kidney disease G5 (CKD G5) who are receiving hemodialysis (CKD G5HD) and have already undergone a trial of a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI) without achieving the desired erythropoietic response.

Clinical scenario

The affected population is adults with anemia and CKD G5 who are receiving hemodialysis. Iron status is a key consideration in this setting: current guidance suggests that iron therapy should be initiated when ferritin is ≤500 ng/ml (≤500 μg/l) and transferrin saturation (TSAT) is ≤30%.

Previous treatment and failure condition

The preceding treatment line involved a trial course of a HIF-PHI agent, selected for ESA hyporesponsiveness after correctable causes had been addressed. The therapeutic goal was a measurable rise in hemoglobin within 3–4 months, monitored at 2–4 weeks after initiation and every 4 weeks thereafter.

Escalation to this protocol is triggered when that hemoglobin response was not achieved within the expected window — indicating that HIF-PHI therapy was ineffective in this patient.

Next treatment step — partial overview

When HIF-PHI therapy proves ineffective or harmful, red blood cell transfusion may be considered as part of a comprehensive treatment strategy. The decision is based on the patient's symptoms and signs caused by anemia — not on reaching an arbitrary hemoglobin threshold. There are additional specific considerations for patients who are transplant candidates.

The full protocol details the precise criteria, clinical decision points, and conditions under which this approach applies.

References DOI: 10.1016/j.kint.2025.06.006

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).
In people with CKD and chronic anemia, consider that the benefits of RBC transfusion may outweigh its harms in people in whom ESA or HIF-PHI therapy is ineffective (e.g., those with hemoglobinopathies, bone marrow failure, or ESA or HIF-PHI resistance) or ESA or HIF-PHI therapy may be harmful (e.g., those with previous or current malignancy or previous stroke).
In people with anemia and CKD, base the decision to transfuse on symptoms and signs caused by anemia rather than an arbitrary Hb threshold.

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