Real-world use of HIF-PH inhibitors in the Japan dialysis and practice patterns study (J-DOPPS, 2019–2022)

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a novel therapeutic alternative to erythropoiesis-stimulating agents (ESAs) for anemia in chronic kidney disease. Evidence regarding their real-world effectiveness is still limited. We analyzed data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS, 2019–2022) to assess the real-world effectiveness of HIF-PHIs among maintenance hemodialysis patients. We compared patients who transitioned from ESAs to HIF-PHIs with those who continued ESAs, focusing on baseline characteristics and changes in anemia-related, iron metabolism, and inflammatory parameters. Among 1433 patients on ESAs, only 56 (3.9%) were switched to HIF-PHIs. Compared with the ESA continuation group, patients in the HIF-PHI group had poorer nutritional status (albumin: 3.3 vs. 3.6 g/dL; cholesterol: 142 vs. 156 mg/dL; respectively) and greater ESA resistance (erythropoietin resistance index: 18.4 vs. 8.5 IU/kg/week/g/dL, respectively), despite higher ESA doses and iron prescription rates. After switching, a significant increase in hemoglobin was observed at 1 month (+0.44 g/dL; 95% confidence interval: 0.05–0.82; p = 0.025). Serum iron and total iron-binding capacity levels also increased, while transferrin saturation and ferritin remained unchanged. A subgroup analysis suggested greater hemoglobin response in patients with high C-reactive protein levels (p for interaction = 0.074), but no difference by erythropoietin resistance index (p for interaction = 0.372). In routine clinical practice, HIF-PHIs were selectively prescribed to patients with treatment-refractory anemia. Treatment increased hemoglobin levels, with a suggestive trend toward greater effect among those with inflammation, supporting the potential utility of HIF-PHIs in complex anemia management.