Intravenous iron and erythropoiesis‐stimulating agents in haemodialysis: A systematic review and meta‐analysis

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Iron deficiency anaemia is common in patients with chronic kidney disease (CKD), and this may be exacerbated by the use of erythropoiesis‐stimulating agents (ESAs).1 Patients with CKD requiring haemodialysis (HD) are at increased risk of iron deficiency anaemia as they are subject to repeated blood loss due to retention of blood in the dialyser and blood lines, frequent blood sampling for laboratory testing, and blood loss from surgical procedures, as well as reduced iron absorption due to inflammation and hepcidin upregulation, exacerbated by concomitant medications such as gastric acid inhibitors and phosphate binders.2
There have been recent concerns around the toxicity of injectable ESAs (thromboembolic events and recurrent malignancies), which could be related to higher dosages of ESA used and consequently increased circulating blood levels of the ESA, rather than the target haemoglobin achieved.4 Moreover, iron deficiency is a common cause of hyporesponsiveness to ESAs, whether it is absolute or functional in nature. Beyond this, there has been a call for more conservative dosing strategies5 due to concerns with ESA‐associated cardiovascular morbidity.6
As such, international treatment guidelines10 strongly recommend the monitoring of iron status and the treatment of iron deficiency with intravenous (IV) iron ± ESA in patients undergoing chronic HD. Although it is generally accepted that the treatment of iron deficiency with IV iron allows a reduction in ESA dose, quantification of the magnitude of the reduction is challenging, because of heterogeneity in study designs that could allow this assessment.
Three systematic reviews of the use of IV iron in patients with CKD have been identified in the medical literature. In 2008, Rozen‐Zvi et al. assessed trials of IV iron versus oral iron in patients with CKD, including those undergoing dialysis.14 The same group have recently repeated this exercise in the light of more recent literature.15 A Cochrane review comparing IV iron with oral iron in adults and children with CKD was published in 2012, 1 and a separate meta‐analysis was published in 2014 to assess the safety and efficacy of IV iron in HD patients with functional iron deficiency.16 The percentage reduction in ESA dose from baseline, however, was not reported in any of these reviews.
The aim of this meta‐analysis was to evaluate the magnitude of the effect (reduction) on ESA dosing when IV iron doses, (consistent with the Kidney Disease Improving Global Outcomes (KDIGO) guidelines), were administered in an adult HD population.
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