LETTER
How Much Intravenous Iron Is Utilized for Erythropoiesis? To the Editor: We thank Kshirsagar et al1 for the article “The Comparative Short-Term Effectiveness of Iron Dosing and Formulations in US Hemodialysis Patients.” This important retrospective cohort study compared the effects of different intravenous iron (IVFe) dosages on hemoglobin (Hb) and serum ferritin (FRT) levels and on epoetin (EPO) doses during 6 weeks of follow-up using data from USRDS. However, we question the authors’ conclusion that strategies favoring large doses of IVFe lead to improvements in the management of anemia. In comparing bolus doses (exceeding 600 mg) and maintenance doses during 1 month, the bolus doses were associated with higher average adjusted Hb (þ0.23 g/dL) and FRT (þ151 mg/L) levels and a lower average EPO dose (464 units) compared with the maintenance doses. Although the increase in the FRT level was remarkable, the increase in Hb was extremely small. This article does not provide information about the exact dose of IVFe administered during the follow-up period; however, we may conclude that a substantial amount of iron was accumulated in the body, as reflected by the change in FRT. Even if we assume that the ratio of stored iron to FRT in the hemodialysis patients was one-half of that in the healthy controls (8 mg iron storage: 1 mg/L FRT), more than 600 mg of iron would still have accumulated in the bodies of the hemodialysis patients. In contrast, based on the increase in Hb (0.2-0.3 g/dL), we estimate that only 30-50 mg of the IVFe was used for erythropoiesis, although the administration of IVFe accelerated erythropoiesis and decreased the EPO Funding: None. Conflict of Interest: None. Authorship: All the authors had access to all the data and contributed to the drafting of this manuscript.
0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved.
dose. Thus, because the entire bodies of healthy people contain 3000-5000 mg of iron, we also may conclude that IVFe administration yielded only a small increase in Hb in exchange for the accumulation of a relatively large amount of iron. It may be necessary to estimate whether the accumulated iron could be used for erythropoiesis at a later point. The data indicate that the basal FRT level is >400 mg/L. Consistently, a positive correlation between FRT and hepcidin has been reported; therefore, the hepcidin level under basal conditions should be sufficiently high to halt the release of iron from the reticuloendothelial system (RES).2 Thus, the iron stored in the RES cannot be used for erythropoiesis as long as the FRT level remains high. We should keep in mind that humans have no means of controlling iron excretion or adjusting for excess iron; therefore, the continuation of IVFe could lead to the progressive accumulation of iron in the body. Ultimately, a clinical trial comparing iron dosing strategies may be crucial for developing improved methods of managing anemia. Takeshi Nakanishi, Yukiko Hasuike, Yasuyuki Nagasawa, Takahiro Kuragano,
MD, MD, MD, MD,
PhD PhD PhD PhD
Department of Internal Medicine Division of Kidney and Dialysis Hyogo College of Medicine Nishinomiya, Japan
http://dx.doi.org/10.1016/j.amjmed.2013.05.028
References 1. Kshirsagar AV, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Brookhart MA. The comparative short-term effectiveness of iron dosing and formulations in US hemodialysis patients. Am J Med. 2013;126:541. e1-541.e14. 2. Nakanishi T, Kuragano T, Otaki Y, Kaibe S, Nagasawa Y, Hasuike Y. Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations? Clin Exp Nephrol. 2012;16(9):819-826.
How Much Intravenous Iron Is Utilized for Erythropoiesis? To the Editor: We thank Kshirsagar et al1 for the article “The Comparative Short-Term Effectiveness of Iron Dosing and Formulations in US Hemodialysis Patients.” This important retrospective cohort study compared the effects of different intravenous iron (IVFe) dosages on hemoglobin (Hb) and serum ferritin (FRT) levels and on epoetin (EPO) doses during 6 weeks of follow-up using data from USRDS. However, we question the authors’ conclusion that strategies favoring large doses of IVFe lead to improvements in the management of anemia. In comparing bolus doses (exceeding 600 mg) and maintenance doses during 1 month, the bolus doses were associated with higher average adjusted Hb (þ0.23 g/dL) and FRT (þ151 mg/L) levels and a lower average EPO dose (464 units) compared with the maintenance doses. Although the increase in the FRT level was remarkable, the increase in Hb was extremely small. This article does not provide information about the exact dose of IVFe administered during the follow-up period; however, we may conclude that a substantial amount of iron was accumulated in the body, as reflected by the change in FRT. Even if we assume that the ratio of stored iron to FRT in the hemodialysis patients was one-half of that in the healthy controls (8 mg iron storage: 1 mg/L FRT), more than 600 mg of iron would still have accumulated in the bodies of the hemodialysis patients. In contrast, based on the increase in Hb (0.2-0.3 g/dL), we estimate that only 30-50 mg of the IVFe was used for erythropoiesis, although the administration of IVFe accelerated erythropoiesis and decreased the EPO Funding: None. Conflict of Interest: None. Authorship: All the authors had access to all the data and contributed to the drafting of this manuscript.
0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved.
dose. Thus, because the entire bodies of healthy people contain 3000-5000 mg of iron, we also may conclude that IVFe administration yielded only a small increase in Hb in exchange for the accumulation of a relatively large amount of iron. It may be necessary to estimate whether the accumulated iron could be used for erythropoiesis at a later point. The data indicate that the basal FRT level is >400 mg/L. Consistently, a positive correlation between FRT and hepcidin has been reported; therefore, the hepcidin level under basal conditions should be sufficiently high to halt the release of iron from the reticuloendothelial system (RES).2 Thus, the iron stored in the RES cannot be used for erythropoiesis as long as the FRT level remains high. We should keep in mind that humans have no means of controlling iron excretion or adjusting for excess iron; therefore, the continuation of IVFe could lead to the progressive accumulation of iron in the body. Ultimately, a clinical trial comparing iron dosing strategies may be crucial for developing improved methods of managing anemia. Takeshi Nakanishi, Yukiko Hasuike, Yasuyuki Nagasawa, Takahiro Kuragano,
MD, MD, MD, MD,
PhD PhD PhD PhD
Department of Internal Medicine Division of Kidney and Dialysis Hyogo College of Medicine Nishinomiya, Japan
http://dx.doi.org/10.1016/j.amjmed.2013.05.028
References 1. Kshirsagar AV, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Brookhart MA. The comparative short-term effectiveness of iron dosing and formulations in US hemodialysis patients. Am J Med. 2013;126:541. e1-541.e14. 2. Nakanishi T, Kuragano T, Otaki Y, Kaibe S, Nagasawa Y, Hasuike Y. Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations? Clin Exp Nephrol. 2012;16(9):819-826.
