Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study

Toby Richards,Craig French,Alisa Higgins,Stuart Baker,Simon Towler,Steve Webb,Wendy Erber,Julie McMorrow,Joel Gummer,Bart De Keulenaer,Shannon Farmer,John K. Olynyk,Janet Ferrier,Robert Trengove,Edward Litton,David Hawkins,Axel Hofmann

doi:10.1186/s40560-018-0328-2

Abstract

BackgroundBoth anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement.MethodsWe conducted a prospective observational study nested within a multicenter randomized controlled trial (RCT) of IV iron versus placebo. The study was conducted in the ICUs of four tertiary hospitals in Perth, Western Australia. Critically ill patients with haemoglobin (Hb) of < 100 g/L and within 48 h of admission to the ICU were eligible for participation after enrolment in the IRONMAN RCT. The response to IV iron therapy compared with placebo was assessed according to tertile of hepcidin concentration.ResultsHepcidin concentration was measured within 48 h of ICU admission in 133 patients. For patients in the lower two tertiles of hepcidin concentration (< 53.0 μg), IV iron therapy compared with placebo was associated with a significant decrease in RBC transfusion requirement [risk ratio 0.48 (95% CI 0.26–0.85), p = 0.013].ConclusionsIn critically ill patients with anaemia admitted to an ICU, baseline hepcidin concentration predicts RBC transfusion requirement and is able to identify a group of patients in whom IV iron compared with placebo is associated with a significant decrease in RBC transfusion requirement.Trial registrationAustralian New Zealand Clinical Trials Registry: ANZCTRN12612001249 Registered 26/11/2012

Highlights

Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU)
Baseline hepcidin levels were available for 133 (95%) out of the 140 participants enrolled in the IRONMAN randomized controlled trial (RCT)
There was no significant correlation between hepcidin concentration and baseline C reactive protein or iron indices

Summary

Introduction

Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement. Recent randomized controlled trials (RCTs) of IV iron therapy in critically ill patients have not demonstrated benefit [5, 6]. This may be because critical illness results in an acute inflammatory response that confounds the interpretation of standard, clinically available measures of iron deficiency used in these studies. Hepcidin may be more accurate in predicting an increase in red blood cell production in response to IV iron, prospective clinical data is lacking

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