Roxadustat induced fetal hemoglobin in anemic CKD patients: a dual-center real-world observational cohort study.

BACKGROUND: Induction of fetal hemoglobin (HbF) expression is a promising therapeutic approach for hemoglobinopathies. HbF is primarily regulated by hypoxia-inducible factor (HIF). Roxadustat, an oral HIF prolyl hydroxylase inhibitor (HIF-PHI), is utilized in the treatment of chronic kidney disease (CKD) patients with anemia. Its capacity to induce HbF has been demonstrated in cell and animal models, but not in humans. METHODS: In this dual-center, prospective, real-world, non-randomized observational cohort study, we initially enrolled 85 anemic CKD patients receiving distinct anti-anemia treatments. Following post hoc exclusion of participants with insufficient follow-up data, we analyzed the data of 52 patients, comprising those in the oral Roxadustat group (n = 27) and the subcutaneous erythropoiesis-stimulating agent (ESA) group (n = 25). HbF levels were monitored every four weeks by measuring the percentage of HbF-positive red blood cells (F-cells) and mean corpuscular fetal hemoglobin (MCHbF). RESULTS: Roxadustat administration showed progressive elevation of HbF levels, however, the ESA group exhibited only minor nonprogressive HbF fluctuations throughout the observation period. Significant differences in the increase of F-cells percentage and MCHbF between the two groups were observed at week 4 and amplified at week 8 and 12. Only one patient in the Roxadustat group exhibited clinically significant hypothyroidism requiring levothyroxine replacement. Safety monitoring was limited to clinically evident events reported during routine visits; consequently, subclinical abnormalities or mild adverse events were not systematically documented. CONCLUSION: Our study suggested that Roxadustat has the potential to induce HbF expression in anemic CKD patients. STUDY REGISTRATION: The study was registered retrospectively in the Chinese Clinical Trial Registry (ChiCTR, https://www.chictr.org.cn) under the identifier ChiCTR2500096786 on February 6, 2025.