High-flux hemodialysis + HIF-PHI significantly improves renal anemia markers over rhEPO in uremia patients

Patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis frequently suffer from renal anemia, a complex condition impacting quality of life and survival. Traditional treatment with recombinant human erythropoietin (rhEPO) often requires high doses, can lead to iron deficiency, and may not fully address the underlying pathophysiology. The emergence of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) offers a novel approach by stabilizing HIF-α, promoting endogenous erythropoietin production, and improving iron utilization. This study investigates whether combining HIF-PHI with high-flux hemodialysis (HFHD) can offer superior outcomes for renal anemia compared to conventional rhEPO and low-flux hemodialysis (LFHD).

This randomized controlled trial enrolled 64 newly treated maintenance hemodialysis patients, divided into 4 groups of n=16 each: LFHD + rhEPO, LFHD + HIF-PHI, HFHD + rhEPO, and HFHD + HIF-PHI. All patients received hemodialysis 3 times per week, with each session lasting 4 hours, for a total duration of 2 months. Researchers measured changes in primary endpoints including hemoglobin (HB) and red blood cells (RBC), alongside secondary markers of iron metabolism (hepcidin, TIBC, ferritin, TSAT), bone metabolism (PTH), and middle-molecule clearance (β2-microglobulin). The incidence of adverse events was also monitored.

All treatment groups demonstrated significant increases in HB and RBC levels post-treatment (P < .05). However, the improvements were notably superior in the HIF-PHI arms. Specifically, the increases in hemoglobin (ΔHB) and RBC (ΔRBC) were significantly greater in the HFHD + HIF-PHI and LFHD + HIF-PHI groups compared to the LFHD + rhEPO and HFHD + rhEPO groups.

Posttreatment hepcidin levels were significantly reduced in both HIF-PHI groups (HFHD + HIF-PHI and LFHD + HIF-PHI) compared to pretreatment, indicating improved iron availability. Concurrently, total iron-binding capacity (TIBC) and transferrin saturation (TSAT) were significantly higher in the HIF-PHI groups post-treatment (P < .05). Furthermore, posttreatment parathyroid hormone (PTH) and β2-microglobulin (β2-MG) levels were lower in the HFHD + HIF-PHI and HFHD + rhEPO groups than in the two LFHD groups (P < .05), suggesting better clearance of middle-molecule toxins with high-flux dialysis. While the incidence of adverse reactions was numerically lower in the HIF-PHI groups, this difference did not reach statistical significance.