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Abstract: TH-PO974

Validate Optimal Iron Management When Using Hypoxia-Inducible Factor-Prolyl Hydroxylase Domain Inhibitor (HIF-PHI) in Renal Anemia: Excessive Iron Administration Is Unnecessary

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism


  • Ogawa, Chie, Maeda Institute of Renal Research, Kawasaki, Kanagawa, Japan
  • Tsuchiya, Ken, Department of Blood Purification, Tokyo Women’s Medical University, Tokyo, Japan
  • Maeda, Kunimi, Maeda Institute of Renal Research, Kawasaki, Kanagawa, Japan

Hypoxia-inducible factor prolyl hydroxylase domain inhibitors (HIF-PHIs), new therapeutic agent for renal anemia, shows its effects through a mechanism not only by transcription factor-mediated erythropoietin production but also by iron metabolism. Therefore, although the importance of iron supplementation has been emphasized, it is presumed that iron utilization is also promoted endogenously and that a mischievous iron overdose is not necessary. In the present study, we examined optimal iron management under HIF-PHI administration.


The subjects were 30 maintenance hemodialysis patients who switched from darbepoetin alfa (DA) to Roxadustat (Rox). To examine iron kinetics during the switchover, reticulocyte hemoglobin content (CHr), which reflects recent Hb synthesis, was measured in addition to conventional iron-related parameters. The iron-regulated hormone hepcidin was also measured. Iron deficiency was defined as CHr<32.0 pg. ROC curves were used to determine cut off values for the point at which CHr sufficiency was met.


After the switching to Rox, there was a significant increase in Hb and RBC and a decrease in ferritin and hepcidin (all, p<0.01), suggesting increased iron demand. In the results of the ROC curve with the endpoint CHr≥32pg on Day0, cutoff values for s-ft and TSAT were respectively 49.7 ng/mL and 21.6% on Day 0 and 35.5 ng/mL and 16.2% on Day 28. With the endpoint CHr ≥ 32.0 pg on Day 28, cutoff values for s-ft and TSAT on Day 0 were 81.6 ng/mL and 23.9%, respectively.
In a patient with s-ft 184 ng/mL and TSAT 10.6%, there was a rapid increase in Hb from 8.0 to 10.0 g/dL after 2 weeks of switching.


The present study suggests that a serum ferritin of at least 81.6 ng/mL at the time of switching, and most recently 35.5 ng/mL, may avoid iron deficiency when switching from DA to Rox. Iron deficiency is pointed out to increase the risk of thrombosis due to hypercoagulability and increased platelet count. In our previous report (Acta Haematol 2022), the cutoff value of ferritin for platelet increase was 77.2 ng/ml (area under the curve 0.76, 95% CI 0.55 – 0.96) when ROX was administered. Moreover, it has also been shown that functional iron deficiency with ferritin sufficiency may result in a rapid rise in Hb. Thus, the amount of iron required at the time of switchover may be less than expected.