Timing-adjusted iron dosing enhances erythropoiesis-stimulating agent-induced erythropoiesis response and iron utilization

Abstract

Background: We recently demonstrated, using an index of recently synthesized hemoglobin, reticulocyte hemoglobin (Ret-Hb), that iron administration remarkably improves hemoglobin (Hb) synthesis during the period of high activation of erythropoiesis induced by the administration of a continuous erythropoietin receptor activator (CERA). We aimed to investigate whether repetition of iron dosing sustains effective erythropoiesis and suppresses iron storage. Methods: In a 3-month comparison of monthly CERA administration, 104 hemodialysis patients were randomized into two groups that received 40 mg iron intravenously 3 times; the first-week iron group [n = 51], given iron in the first week after CERA administration, during the period of high activation of erythropoiesis, and the third-week iron group [n = 53], given iron in the third week at the time of mild erythropoiesis activation. Results: Initial mean CERA dosages were 123.5 ± 67.5 μg/month and did not differ between the groups. Hb levels were not different between the groups throughout the study. One-week increases in Ret-Hb levels after CERA administration were higher, during the first and the third month, in the group given iron in the first week compared with the third-week iron group (241.9 ± 63.3 vs. 196.2 ± 82.8 mg/dL, P = 0.004; 227.2 ± 83.5 vs. 187.9 ± 88.7 mg/dL, P = 0.037, respectively). The increase in ferritin levels was suppressed 3 months later in the first-week iron group compared with that of the third-week iron group (22.3 ± 64.0 vs. 69.0 ± 76.6 ng/mL, P = 0.002). Hepcidin levels decreased 1 week after CERA administration in both groups and were not different between the groups. Conclusions: Timing-adjusted iron administration increased the levels of recently produced Hb and iron utilization and suppressed the ferritin levels. The iron administration timing deserves consideration when optimizing the efficiency of erythropoiesis-stimulating agents in patients undergoing hemodialysis. Trial registration: UMIN000016375. Registered 29 January 2015.