title: Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency.
abstract: Growing awareness that heart failure, renal impairment, and anaemia are frequent co-morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR-HF trial raises a new hypothesis: is it time for 'CRAS' to be supplemented with new acronyms such as CRIDS (cardiorenal-iron deficiency syndrome) or even CRAIDS (cardiorenal-anaemia-iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14-2.17, P = 0.005). In the FAIR-HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron-deficient patients with heart failure, even in non-anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.
authors.affiliation: Department of Renal Medicine, King's College Hospital, London SE5 9RS, UK. iain.macdougall@nhs.net
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.forename: Bernard
authors.initials: B
authors.lastname: Canaud
authors.forename: Angel L M
authors.initials: AL
authors.lastname: de Francisco
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Donald
authors.initials: D
authors.lastname: Silverberg
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000150:complications* / Q000188:drug therapy; D059347:Cardio-Renal Syndrome / Q000188:drug therapy / Q000209:etiology*; D019587:Dietary Supplements; D006333:Heart Failure / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D019266:Iron, Dietary / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019266:Iron, Dietary