Abstract
Background and ObjectivesIron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients.Design, Setting, Participants and MeasurementsWe performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis.ResultsThe CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI.ConclusionsThe standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products.
Highlights
During the past two decades, routine use of erythropoeisis-stimulating agents (ESA) has enabled anemia to be corrected in most patients with end-stage renal disease, thereby improving their quality of life and reducing associated morbidity [1, 2]
We found that 84% of a cohort of 119 fit hemodialysis patients had hepatic iron overload on magnetic resonance imaging without gadolinium (MRI) ($51 mmol/g dry weight), and that 30% of these 119 patients had severe iron overload ($201 mmol/g dry weight) at levels usually seen in genetic hemochromatosis [6, 7]
Iatrogenic iron overload may be prevalent among dialysis patients, favored in the USA and many other industrialized countries by recent implementation of reimbursement policies leading to an increase in the use of intravenous iron preparations aimed at reducing the cost of ESA, together with a possible excessive advocated dose of intravenous iron and, possibly, erroneous target values for biological markers of iron metabolism [6, 8, 9]
Summary
During the past two decades, routine use of erythropoeisis-stimulating agents (ESA) has enabled anemia to be corrected in most patients with end-stage renal disease, thereby improving their quality of life and reducing associated morbidity [1, 2]. Iron overload was considered rare among dialysis patients in the ESA era [5] We recently challenged this view, after studying liver iron stores by quantitative magnetic resonance imaging without gadolinium (MRI), the gold-standard method for estimating and monitoring iron stores [6, 7]. Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Conclusions: The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products
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