title: A 3-marker index improves the identification of iron disorders in CKD anaemia.
abstract: BACKGROUND
  Iron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia.
  
  
  METHODS
  We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total iron binding capacity (TIBC<50 µmol/L) in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR) by (51)Cr-EDTA renal clearance; 199 also had hepcidin measures.
  
  
  RESULTS
  The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID) to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m(2) (interaction p<0.0001). In patients with mGFR<30 mL/min/1.73 m(2), the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia.
  
  
  CONCLUSIONS
  The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m(2). Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1018, CESP Centre for research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity, and Kidney Diseases Team, Villejuif, France ; Department of Nephrology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Mercadal
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1018, CESP Centre for research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity, and Kidney Diseases Team, Villejuif, France ; Univ Paris Sud 11, UMRS 1018, Villejuif, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Metzger
authors.affiliation: Department of Physiology and Nephrology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France ; Institut National de la Santé et de la Recherche Médicale U702, Paris, France.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Haymann
authors.affiliation: Department of Nephrology, Hôpital Européen G Pompidou, Assistance Publique-hôpitaux de Paris, Université Paris Descartes, Paris, France ; Institut National de la Santé et de la Recherche Médicale UMR S775, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U702, Paris, France ; Department of Nephrology, Hôpital Tenon, Assistance Publique-hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: Department of Physiology, Hôpital Bichat, Assistance Publique-hôpitaux de Paris, Paris, France ; Institut National de la Santé et de la Recherche Médicale U699, Université Paris Diderot, Paris, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Flamant
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U699, Université Paris Diderot, Paris, France ; Department of Nephrology, Hôpital Bichat, Assistance Publique-hôpitaux de Paris, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Vrtovsnik
authors.affiliation: Department of Physiology, Hôpital Européen G Pompidou, Assistance Publique-hôpitaux de Paris, Université Paris Descartes, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Gauci
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1018, CESP Centre for research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity, and Kidney Diseases Team, Villejuif, France ; Department of Physiology, Hôpital Européen G Pompidou, Assistance Publique-hôpitaux de Paris, Université Paris Descartes, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1018, CESP Centre for research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity, and Kidney Diseases Team, Villejuif, France ; Univ Paris Sud 11, UMRS 1018, Villejuif, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Stengel
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012307:Risk Factors; D012737:Sex Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D014168:Transferrin; D005293:Ferritins; D007501:Iron