Maximal Standard Dose of Parenteral Iron for Hemodialysis Patients: An MRI-Based Decision Tree Learning Analysis

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.

Annual Iron Loss Associated with Hemodialysis

“…However, bolus iron supplementation may increase non-transferrin binding iron and cause iron toxicity, leading to oxidative stress, susceptibility to bacterial infection, endothelial damage and liver injury [19][20][21][22] . The unintended accumulation of iron in the liver has been reported in an MRI study when >250 mg of intravenous iron was administered in 1 month [23] . Hb cycling, which might be related to cardiovascular events, has also been induced by intensive iron supplementation [24,25] .…”

Iatrogenic iron overload and its potential consequences in patients on hemodialysis

“…The CHAID algorithm splits the patients according to the monthly IV iron dose, with a single cutoff of 250 mg/month. The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with more than 250 mg of IV iron/ month versus less than 250 mg/month [87]. This MRI study suggests that the standard maximal monthly IV iron dose should be lowered to 250 mg to lessen the risk of iron overload in dialysis patients and seems to be in good agreement with the 3 recently published long-term epidemiological studies [12][13][14]87].…”

“…The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with more than 250 mg of IV iron/ month versus less than 250 mg/month [87]. This MRI study suggests that the standard maximal monthly IV iron dose should be lowered to 250 mg to lessen the risk of iron overload in dialysis patients and seems to be in good agreement with the 3 recently published long-term epidemiological studies [12][13][14]87]. The worldwide nephrology community is also rediscovering the ingenious, cautious Japanese strategy of iron therapy, which maintains optimal hemoglobin levels (somewhat lower than in western countries) with minimal use of IV iron products and lower ferritin levels [21,88].…”

“…A recent cohort study of hemodialysis patients, combining quantitative MRI with data-mining yielded nontoxic doses of IV iron, thereby improving the safety of parenteral iron products in dialysis patients [87]. 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 a prospective cohort of 199 hemodialysis patients treated for anemia with parenteral iron-sucrose and an ESA, in keeping with current clinical guidelines [87].…”

“…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 a prospective cohort of 199 hemodialysis patients treated for anemia with parenteral iron-sucrose and an ESA, in keeping with current clinical guidelines [87]. Hepatic iron stores were measured blindly by T1 and T2* contrast MRI, without gadolinium, coupled with CHi-squared Automatic Interaction Detection analysis (CHAID) [87].…”