Intravenous iron therapy in non-dialysis CKD patients

Abstract

Iron deficiency anaemia in non-dialysis-dependent chronic kidney disease patients is common, with a study (admittedly from more than 10 years ago) suggesting that >800 000 such patients in the USA are affected [1]. This may significantly impact on quality of life and exercise capacity, and it is also associated with significant morbidity and mortality. Correction of the anaemia will require iron replacement therapy, with or without erythropoiesis-stimulating agents (ESAs). The optimum route of administration of iron is controversial, with a wide variability in clinical practice among different countries, different renal units and indeed among different nephrologists within the same unit. The use of oral versus intravenous iron as the first-line management of this condition varies, partly because of the individual nephrologist’s beliefs and also partly due to a paucity of scientific evidence in this clinical setting, but is also influenced by the accessibility to a service that is readily able to provide intravenous iron supplementation. Thus, in primary care, general practitioners are likely to start with oral iron, whereas renal units that support an intravenous iron clinic (usually nurse-led) are more likely to start with intravenous iron. Reimbursement policies for intravenous iron in the non-dialysis CKD setting are also variable throughout the world, and this too may impact on the relative use of IV versus oral iron. Until recently, with the exception of iron dextran-containing preparations (which themselves have generated concerns about anaphylactic or hypersensitivity reactions), the available intravenous iron compounds were unable to provide high doses of iron as a single administration. Thus, for iron gluconate (used in the USA, Italy and Germany), doses of 62.5–125 mg of iron were the maximum recommended at a single sitting [2], whereas for iron sucrose (IS) - used widely in the USA, Europe, and Australia, bolus doses of up to only 200 mg were recommended [3]. Thus, many patients were required to attend for repeated boluses of IV iron, e.g. three or more injections of IS, 200 mg at a time, to replenish their iron deficits. Within the last few years, three new intravenous iron preparations have been licensed [4]. These include ferumoxytol (Feraheme® in the USA; Rienso® in Europe), ferric carboxymaltose (FCM, Ferinject® in Europe; Injectafer® in the USA) and iron isomaltoside-1000 (Monofer® in Europe). Data comparing these new preparations to the more traditional IV iron compounds are sparse, with small numbers of patients included in the clinical trials, most of which were not randomized, and with short follow-up. Qunibi et al .[ 5] performed a randomized controlled trial comparing intravenous FCM with oral iron for the treatment of iron deficiency anaemia in nondialysis-dependent chronic kidney disease patients, and showed that the response to intravenous iron was slightly greater with intravenous iron compared with oral iron, with an acceptable safety profile. However, the total number of patients exposed to intravenous FCM was 152 and the period of follow-up was only 8 weeks. In another recent randomized controlled trial, Charytan et al .[ 6] administered 15 mg/kg of FCM intravenously up to a maximum of 1000 mg in 204 nondialysis CKD patients and compared the haemoglobin responses with a group of patients treated with standard medical care (IV, oral or no iron, as determined by the investigator). Otherwise, head-to-head comparisons of IV iron preparations in the non-dialysis CKD population have been lacking. Onken et al. [7], in this issue of Nephrology Dialysis Transplantation, however, have gone some way to correcting this deficit in the evidence base, by reporting the results of the REPAIR-IDA trial. This was a large randomized controlled