Effect of Maintenance Intravenous Iron Treatment on Erythropoietin Dose in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial

Abstract

Background: There is no consensus on intravenous (IV) iron supplement dose, schedule, and serum ferritin target in functional iron deficiency anemia to maintain optimum target levels of iron stores by several guidelines. Objective: To examine the effect of IV iron supplementation to different targets of serum ferritin on erythropoietin dose and inflammatory markers in chronic hemodialysis (HD) patients with functional iron deficiency anemia. Design: A multicenter, randomized, open-label study. Setting: In a developing country, Thailand. Patients: Chronic HD patients with functional iron deficiency anemia. Measurements: Erythropoietin resistance index, high-sensitivity C-reactive protein, and fibroblast growth factor 23. Methods: Two hundred adult chronic HD patients with transferrin saturation less than 30% and serum ferritin of 200 to 400 ng/mL were randomized 1:1 to maintain serum ferritin 200 to 400 ng/mL (low-serum ferritin group, N = 100) or 600 to 700 ng/mL (high-serum ferritin group, N = 100). During a 6-week titration period, participants randomized to the high-serum ferritin group initially received 600 mg IV iron (100 mg every week), while the participants in the low-serum ferritin group did not receive IV iron. During the 6-month follow-up period, the dose of IV iron was adjusted by protocol. Results: The mean dose of IV iron was 108.3 ± 28.2 mg/month in the low-serum ferritin group and 192.3 ± 36.2 mg/month in the high-serum ferritin group. The mean serum ferritin was 367.0 ± 224.9 ng/mL in the low ferritin group and 619.6 ± 265.2 ng/mL in the high ferritin group. The erythropoietin resistance index was significantly decreased in the high-serum ferritin group compared to the low-serum ferritin group after receiving IV iron in the 6-week titration period (mean difference: −113.43 ± 189.14 vs 41.08 ± 207.38 unit/week/g/dL; P < .001) and 3-month follow-up period (mean differences: −88.88 ± 234.43 vs −10.48 ± 217.75 unit/week/g/dL; P = .02). Limitations: Short follow-up period. Conclusion: Maintaining a serum ferritin level of 600 to 700 ng/mL by IV iron administration of approximately 200 mg per month as a maintenance protocol can decrease erythropoietin dose requirements in chronic HD patients with functional iron deficiency anemia. Trials registration: The study was registered with the Thai Clinical Trials Registry TCTR20180903003.

Maintenance intravenous iron in hemodialysis patients to minimize erythropoietin doses: a double-blinded, randomized controlled trial (the MAINTAIN IRON trial)

“…Susantitaphong et al 11 conducted a randomized control trial in chronic hemodialysis patients with Hb 8–12 g/dl, ferritin 200–400 ng/ml, and TSAT < 30%. They prescribed IV iron as a maintenance regimen to maintain either a high ferritin level (600–700 µg/dl) or a low one (200–400 µg/dl).…”

“…The median monthly iron was 264 mg; thus, it remained challenging to determine appropriate doses of maintenance IV iron therapy. Susantitaphong et al 11 conducted a randomized control trial in chronic hemodialysis patients with Hb 8-12 g/ dl, ferritin 200-400 ng/ml, and TSAT < 30%. They prescribed IV iron as a maintenance regimen to maintain either a high ferritin level (600-700 µg/dl) or a low one (200-400 µg/dl).…”

High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study

“…Although the effectiveness of erythropoiesis-stimulating agents has been verified in patients using maintenance haemodialysis [ 9 , 16 ], data in the patient population remain limited. In a recent randomized study [ 22 ], 200 chronic haemodialysis patients with functional iron deficiency anaemia in Thailand were included. These patients with transferrin saturation of < 30% and serum ferritin of 200–400 ng/mL were randomized 1:1 to maintain serum ferritin at either 200–400 ng/mL or 600–700 ng/mL.…”