The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin

Nephrol Dial Transplant. 2001 Jul;16(7):1416-23. doi: 10.1093/ndt/16.7.1416.


Background: Iron deficiency (ID) is the main cause of hyporesponsiveness to erythropoietin in haemodialysis patients and its detection is of value since it is easily corrected by intravenous iron. Markers of iron supply to the erythron, including erythrocyte zinc protoporphyrin (Er-ZPP), percentage of hypochromic erythrocytes (Hypo), reticulocyte haemoglobin content (CHr) and soluble transferrin receptor (sTfR), may be more accurate predictors of ID than ferritin (Fer) and transferrin saturation (TSat), but relative diagnostic power and best threshold values are not yet established.

Methods: In 125 haemodialysis patients on maintenance erythropoietin, the diagnostic power of the above parameters was evaluated by ROC curve, multivariate regression, and stepwise discriminant analyses. Diagnosis of ID was based on haemoglobin response to intravenous iron (992 mg as sodium ferric gluconate complex over an 8-week period).

Results: Fifty-one patients were considered iron deficient (haemoglobin increase by 1.9+/-0.5 g/dl) and 74 as iron replete (haemoglobin increase by 0.4+/-0.3 g/dl). ROC curve analysis showed that all tests had discriminative ability with the following hierarchy: Hypo (area under curve W=0.930, efficiency 89.6% at cut-off >6%), CHr (W=0.798, efficiency 78.4% at cut-off < or =29 pg), sTfR (W=0.783, efficiency 72.4% at cut-off >1.5 mg/l), Er-ZPP (W=0.773, efficiency 73.0% at cut-off >52 micromol/mol haem), TSat (W=0.758, efficiency 70.4% at cut-off <19%) and ferritin (W=0.633, efficiency 64.0% at cut-off <50 ng/ml). Stepwise discriminant analysis identified Hypo as the only variable with independent diagnostic value, able to classify 87.2% of patients correctly. Additional tests did not substantially improve diagnostic efficiency of Hypo >6% alone.

Conclusions: In haemodialysis patients on maintenance erythropoietin, Hypo >6% is the best currently available marker to identify those who will improve their response after intravenous iron. Cost-effectiveness suggests that this parameter should be a first-line tool to monitor iron requirements in clinical practice.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Biomarkers / blood
  • Cohort Studies
  • Erythrocytes / metabolism
  • Erythropoietin / therapeutic use
  • Ferric Compounds / therapeutic use*
  • Hemoglobins / analysis
  • Humans
  • Iron Deficiencies
  • Multivariate Analysis
  • Predictive Value of Tests
  • Protoporphyrins / blood
  • ROC Curve
  • Receptors, Transferrin / blood
  • Recombinant Proteins
  • Renal Dialysis*
  • Reticulocytes / metabolism
  • Transferrin / analysis


  • Biomarkers
  • Ferric Compounds
  • Hemoglobins
  • Protoporphyrins
  • Receptors, Transferrin
  • Recombinant Proteins
  • Transferrin
  • Erythropoietin
  • zinc protoporphyrin
  • ferric gluconate