Serum hepcidin potentially identifies iron deficiency in survivors of critical illness at the time of hospital discharge

Shah, Akshay; Wray, Katherine; James, Timothy; Shine, Brian; Morovat, R; Stanworth, Simon; McKechnie, Stuart; Kirkbride, Rachael; Griffith, David; Walsh, Timothy; Drakesmith, Hal; Roy, Noémi

doi:10.1111/bjh.15067

Cited by 17 publications

(25 citation statements)

References 9 publications

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“…In our study, we observed an important reduction (around 50%) of D90 mortality rate in the intervention arm in both intention-to-treat and sub-group analyses. This is consistent with the observed increase in mortality reported in critically ill patients with low hepcidin at discharge from ICU [14,15]. This is also in line with the results of a recent study in hemodialysis patients, showing that treating ID with higher doses of iron reduces the number of hospitalization episodes (for heart failure) [31] and with improved outcome observed in ID treatment of heart failure patients [32].…”

Section: Discussionsupporting

confidence: 90%

“…Our results demonstrate that iron de ciency may be recognized in a large proportion of critically ill patients (more than 50%). This is consistent with the high proportion of ID observed on ICU admission (between 20-40% using different parameters) [5][6][7] and with the proportion of ID (de ned as a low hepcidin concentration) we and others reported [14,15]. These prevalence are much higher than the ones observed using standard laboratory tests (less than 10%) [9], con rming the interest of hepcidin quanti cation as a new ID diagnostic method.…”

Section: Discussionsupporting

confidence: 90%

“…Indeed, giving intravenous iron to patients without ID may increase the risk of iron side-effects and of iron overload; whereas giving iron in critically ill patients with ID does not expose to an increased risk of oxidative stress [24]. Second, we used a new biomarker to identify ID, hepcidin [4,5,14,15], because standard laboratory tests are not usable in presence of in ammation [13,25,26]. We used a validated mass spectrometry method [17], which is relatively cheap and easy to obtain .…”

Section: Discussionmentioning

confidence: 99%

“…In the last decades, the understanding of iron metabolism has been markedly improved by the discovery of its master regulator, hepcidin [4]. A low hepcidin level has been shown to indicate ID in critically ill patients [4,5,14,15]. Data on hepcidin analysis in ICU suggests that 37% of patients have ID on ICU discharge and this group of patients had worse outcomes at one year, a low hepcidin being an independent predictor of one-year post-ICU mortality [15].…”

Section: Icumentioning

confidence: 99%

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Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

Lasocki

Asfar

Jaber

et al. 2020

Preprint

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Background: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnosed in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. Methods: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm patients were treated with intravenous iron (1g of ferric carboxymaltose) when hepcidin was <20 μg/l and with intravenous iron and erythropoietin for 20≤ hepcidin <41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue and day 90 mortality. Results: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). 220(55%) had ID at discharge (i.e. an hepcidin <41 μg/l). Primary endpoint was not different (medians(IQR) post-ICU LOS 33(13;90) vs 33(11;90) days for intervention and control respectively, median difference -1(-3;1) days, p=0.78). D90 mortality was significantly lower in the intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference -8.7 (-15.1 to -2.3)%, p=0.008). Conclusion: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but may reduce the long-term mortality in critically ill patients about to be discharged after a prolonged stay. Trial Registration: www.clinicaltrial.gov NCT02276690 (October 28, 2014; Retrospectively registered)

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Icumentioning

confidence: 99%

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Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

Lasocki

Asfar

Jaber

et al. 2020

Preprint

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“…ferritin, transferrin saturation) have limited utility in critically ill patients as the relationship between these markers and iron status is heavily confounded by inflammation. Hepcidin may be a better marker of iron status in critically ill patients, even in the presence of inflammation, 8,9 and recent work supports the hypothesis that critically ill patients have potentially iron-responsive anaemia which may not be detectable with currently available tests. One study suggested that 35% of ICU survivors developed evidence of iron deficiency six months after ICU stay.…”

Section: Introduction Backgroundmentioning

confidence: 88%

INtravenous Iron to Treat Anaemia following CriTical care (INTACT): A protocol for a feasibility randomised controlled trial

Shah

Marian

Dutton

et al. 2019

Journal of the Intensive Care Society

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Background Anaemia is common in patients who survive critical illness and is associated with high levels of fatigue and poor quality of life. In non-critically ill patients, treating anaemia with intravenous iron has resulted in meaningful improvements in quality of life, but uncertainties regarding the benefits, risks, timing and optimal route of iron therapy in survivors of critical illness remain. Methods / Design INtravenous Iron to Treat Anaemia following CriTical care (INTACT) is an open-label, feasibility, parallel group, randomised controlled trial with 1:1 randomisation to either intravenous iron (1000 mg ferric carboxymaltose) or usual medical care. The primary objective is to assess the feasibility of a future, multicentre randomised controlled trial. Participants will be followed up for up to 90 days post-randomisation. The primary outcome measures, which will be used to determine feasibility, are recruitment and randomisation rates, protocol adherence and completeness of follow-up. Secondary outcome measures include collecting clinical, laboratory, health-related quality of life and safety data to inform the power calculations of a future definitive trial. Conclusion Improving recovery from critical illness is a recognised research priority. Whether or not correcting anaemia, with intravenous iron, improves health-related quality of life and recovery requires further investigation. If so, it has the potential to become a rapidly translatable intervention. Prior to embarking on a phase III multicentre trial, a carefully designed and implemented feasibility trial is essential.

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Serum hepcidin potentially identifies iron deficiency in survivors of critical illness at the time of hospital discharge

Cited by 17 publications

References 9 publications

Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

INtravenous Iron to Treat Anaemia following CriTical care (INTACT): A protocol for a feasibility randomised controlled trial

Disorders of red cells and platelets

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