Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study

Abstract

Background and objectives: Iron overload among hemodialysis patients was previously considered rare but is now an increasingly recognized clinical situation. We analyzed correlations between iron biomarkers and the liver iron concentration (LIC) measured by magnetic resonance imaging (MRI), and examined their diagnostic accuracy for iron overload.

Design, setting, participants and measurements: We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 212 hemodialysis patients free of overt inflammation or malnutrition, were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent, in keeping with current clinical guidelines. Blinded measurements of hepatic iron stores were performed by T1 and T2* contrast MRI, and relationships were analysed using Spearman's coefficient, logistic regression and receiver-operator characteristic (ROC) curves.

Results: Among the biological markers, only serum ferritin showed a strong correlation with LIC (rho= 0.52, 95% CI: 0.41-0.61, p< 0.0001, Spearman test). In logistic analysis, only serum ferritin correctly classified the overall cohort into patients with normal liver iron stores (LIC ≤ 50 μmol/g) and those with elevated liver iron stores (LIC > 50 μmol/g) (odds ratio 1.007; 95% CI: 1.004-1.010). Serum ferritin was the iron biomarker with the best discriminatory capacity in ROC curves analysis (area under the curve (AUC) = 0.767; 95% CI: 0.698-0.835). The optimal serum ferritin cutoffs were 160 μg/L for LIC > 50 μmol/g (mild iron overload) and 290 μg/L for LIC > 200 μmol/g (severe iron overload).

Conclusions: For clinical purposes, serum ferritin correctly reflects liver iron stores, as assessed by MRI, in hemodialysis patients without overt inflammation or malnutrition. These results strongly suggest that current ferritin target values should be lowered to avoid iron overload.

Trial registration: ISRCTN Registry 80100088.

Fig 1. Consort flow Diagram.

Fig 2. Histogram of liver iron content measured by quantitative MRI in two cohorts of hemodialysis patients treated with different ferritin and transferrin saturation targets for iron repletion.

Fig 3. Correlations of liver iron stores studied by quantitative MRI with serum ferritin and the soluble transferrin receptor/ferritin ratio in 212 hemodialysis patients.

Fig 4. ROC curves of iron biomarkers for predicting iron overload (LIC > 50 μmol/g) in 212 hemodialysis patients studied by quantitative hepatic MRI.

Fig 5. ROC curve analysis of serum ferritin for predicting iron overload at a cutoff of LIC > 50 and > 200 μmol/g in the overall cohort of 212 hemodialysis patients studied by quantitative hepatic MRI.

Fig 6. ROC Curves of ferritin compared to a combination of the eight biomarkers for predicting iron overload (LIC > 50 μmol/g) in 212 hemodialysis patients studied by quantitative hepatic MRI.