Characteristics associated with efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors in renal anemia patients: a retrospective cohort study

Abstract

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are novel drugs used to treat renal anemia patients.However, their efficacy in elevating hemoglobin levels varies among patients. We aimed to identify characteristics that could influence hemoglobin level in renal anemia patients treated with HIF-PHIs. We conducted a retrospective cohort study in renal anemia patients treated with HIF-PHIs (roxadustat and enarodustat) with CKD stages 3–5 from 2023 to 2025, and both non-dialysis patients and dialysis patients were included. Patients with CKD stage 5 requiring dialysis were classified as having end-stage kidney disease (ESKD), these patients were also included. Patients were assigned into Hb responder or non-responder group based on hemoglobin changes (elevation, non-elevation) from 0 to 3 months. Logistic regression was applied to explore characteristics associated with the effect of HIF-PHI on achieving targeted hemoglobin levels in renal anemia patients. A total of 459 renal anemia patients were included, including 341 and 118 in the Hb responder and non-responder groups, respectively. There were significant differences in lymphocyte percentage, neutrophil percentage, phosphorus, chloride, blood urea nitrogen, and serum creatinine between the Hb responder and non-responder groups ( P < 0.05). A higher probability of Hb response to HIF-PHI therapy was observed when hemoglobin levels were between 100 and 110 g/L. Treatment response was superior when HIF-PHIs were initiated prior to chronic kidney disease stage 4. Logistic regression analysis identified initial hemoglobin levels of 80–90 g/L as an independent risk factor affecting HIF-PHI efficacy, with satisfactory model performance. Renal function stage and electrolyte disturbances were associated with Hb response to HIF-PHIs in patients with renal anemia. Early and appropriate treatment timing may enhance the efficacy of HIF-PHIs to elevate hemoglobin levels in these patients.