Application of high-flux hemodialysis combined with hypoxia-inducible factor prolyl hydroxylase inhibitor in the treatment of renal anemia in patients with uremia: A randomized controlled trial

Background: This study aimed to explore the efficacy of combining high‑flux hemodialysis (HFHD) with a hypoxia‑inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for the treatment of renal anemia among patients with end-stage kidney disease. Methods: Sixty-four newly treated maintenance hemodialysis (MHD) patients were allocated to 4 groups (n = 16 each): low-flux hemodialysis (LFHD) plus recombinant human erythropoietin (rhEPO), LFHD plus HIF-PHI, HFHD plus rhEPO, and HFHD plus HIF‑PHI. All patients underwent hemodialysis 3 times per week, each session lasting 4 hours. After 2 months of treatment, we measured and compared changes in hemoglobin (HB), red blood cells (RBC), hepcidin, total iron‑binding capacity (TIBC), ferritin, transferrin saturation (TSAT), parathyroid hormone (PTH), and β 2 -microglobulin (β 2 -MG), along with the incidence of adverse events in each group. Results: All groups showed increases in HB and RBC post‑treatment ( P <.05). The increases in hemoglobin (ΔHB) and RBC (ΔRBC) were significantly greater in the HFHD + HIF-PHI and LFHD + HIF-PHI groups than in the LFHD + rhEPO and HFHD + rhEPO groups. Posttreatment PTH and β 2 -MG levels were elevated in the LFHD + rhEPO and LFHD + HIF-PHI groups compared with pretreatment ( P <.05). Furthermore, posttreatment PTH and β 2 -MG were lower in the HFHD + HIF-PHI and HFHD + rhEPO groups than in the other 2 groups ( P <.05). Posttreatment hepcidin was significantly reduced in the HFHD + HIF-PHI and LFHD + HIF-PHI groups compared to pretreatment. Posttreatment TIBC and TSAT were higher in the HFHD + HIF-PHI and LFHD + HIF-PHI groups than pretreatment ( P <.05). The incidence of adverse reactions was numerically lower in the HIF-PHI groups than in the rhEPO group, but the difference was not statistically significant. Conclusion: Compared to low-flux dialysis plus rhEPO, the combination of HFHD and HIF-PHI shows more favorable improvements in hemoglobin levels, iron metabolism markers, and clearance of middle-molecule toxins in patients with incident MHD. However, the safety profile requires further evaluation in larger trials.