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Observational Study
. 2018 Nov 21;22(1):314.
doi: 10.1186/s13054-018-2253-0.

Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: an observational prospective study on 1161 patients

Sigismond Lasocki  1 , Thibaud Lefebvre  2   3 , Claire Mayeur  4 , Hervé Puy  2   3 , Alexandre Mebazaa  4 , Etienne Gayat  4 ; FROG-ICU study group
Collaborators, Affiliations
Observational Study

Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: an observational prospective study on 1161 patients

Sigismond Lasocki et al. Crit Care. .

Abstract

Background: Iron deficiency is difficult to diagnose in critically ill patients, but may be frequent and may impair recovery. Measurement of hepcidin could help in the diagnosis of iron deficiency. We aim to assess if iron deficiency diagnosed using hepcidin is associated with poorer outcome one year after an intensive care unit stay.

Methods: We used the prospective FROG-ICU, multicentre (n = 28 ICUs), observational cohort study of critically ill survivors followed up one year after intensive care unit discharge. Iron deficiency was defined as hepcidin < 20 ng/l, ferritin < 100 ng/l or soluble transferrin receptor (sTfR)/log(ferritin) > 0.8, measured in blood drawn at intensive care unit discharge. Main outcomes were one-year all-cause mortality and poor quality of life (defined as a Short Form 36 (SF-36) score below the median).

Results: Among the 2087 patients in the FROG-ICU cohort, 1570 were discharged alive and 1161 had a blood sample available at intensive care unit discharge and were included in the analysis. Using hepcidin, 429 (37%) patients had iron deficiency, compared to 72 (6%) using ferritin alone and 151 (13%) using the sTfR/log(ferritin) ratio. Iron deficiency diagnosed according to low hepcidin was an independent predictor of one-year mortality (OR 1.51 (1.10-2.08)) as was high sTfR/log ferritin ratio (OR = 1.95 (1.27-3.00)), but low ferritin was not. Severe ID, defined as hepcidin < 10 ng/l, was also an independent predictor of poor one-year physical recovery (1.58 (1.01-2.49)).

Conclusions: Iron deficiency, diagnosed using hepcidin, is very frequent at intensive care unit discharge and is associated with increased one-year mortality and poorer physical recovery. Whether iron treatment may improve these outcomes remains to be investigated.

Keywords: Critically ill; Hepcidin; Iron deficiency; Outcome; Quality of life.

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Conflict of interest statement

Ethics approval and consent to participate

This study used data obtained from a previously published study, the FROG-ICU study [18, 19], conducted in France and Belgium in accordance with Good Clinical Practice (Declaration of Helsinki 2002) and Ethical Committee approvals (Comité de Protection des Personnes—Ile de France IV, IRB n° 00003835 and Commission d’éthique biomédicale hospitalo-facultaire de l’hôpital de Louvain, IRB n°B403201213352).

Consent for publication

Not applicable.

Competing interests

Sigismond Lasocki has received speaker honoraria from VIFOR Pharma, MASIMO, LFB and fees as a member of the advisory board and/or Steering Committee from VIFOR Pharma and Pfizer. AM received speaker’s honoraria from Abbott, Novartis, Orion, Roche and Servier, and fees as a member of the advisory board and/or Steering Committee from Cardiorentis, Adrenomed, MyCartis, Neurotronik and Sphyngotec. EG received a research grant from Sphingotec, and consultancy fees from Magnisense and Roche Diagnostics. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow chart. ICU, intensive care unit; pts, patients
Fig. 2
Fig. 2
Relationship between hepcidin and ferritin (a) or soluble transferrin receptor (sTfR)/log(ferritin) (b). We identified positive correlation between log(hepcidin) and ferritin (a) (Pearson’s correlation coefficient [95% CI], 0.59 [0.55–0.62]) and negative correlation with sTfR/log(ferritin) (b). The concordance for iron deficiency (ID) diagnosis according to hepcidin and ferritin (a) was 67%, 95% CI 65–70% (i.e. the proportion of patients with hepcidin < 20 ng/l and ferritin < 100 ng/l or hepcidin > 20 ng/l and ferritin > 100 ng/l) and for sTfR/log(ferritin) (b) it was 71%, 95% CI 68–73%. Grey areas indicate the concordance between the different markers. Lower right (a) and left (b) panels indicate ID according to hepcidin that was not diagnosed according to ferritin (a) or sTfR/log(ferritin) (b). CRP, C-reactive protein
Fig. 3
Fig. 3
Odd ratio for one-year mortality and poor physical quality of life according to the different markers of iron deficiency. Squares indicate crude odd ratios and open circles indicate adjusted OR for main cofounding factors (age, gender, diabetes mellitus, liver disease, surgical/medical admission, septic shock and haemoglobin at discharge ). Poor physical recovery was defined as a physical component of the Short Form 36 score below the median value (i.e. 53) at one year. The SF-36 was available in 466 patients at one year. OR, odds ratio; 95% CI, 95% confidence interval, sTfR, soluble transferrin receptor
Fig. 4
Fig. 4
One-year survival distribution. Survival curves in patients with iron deficiency (ID) (dark line) and patients without ID (non-ID) (dotted line), according to hepcidin < or ≥ 20 ng/l at discharge) are shown from ICU discharge to day 360. Survival was longer in patients without ID (hazard ratio = 1.41 [1.10–1.89], p = 0.01)
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