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

Abstract

Background and ObjectivesIron 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 MeasurementsWe 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.ResultsAmong 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).ConclusionsFor 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 RegistrationISRCTN Registry 80100088

Iatrogenic iron overload and its potential consequences in patients on hemodialysis

“…Ferritin correlated with LIC in both the Italian and French studies, but not in the Australian study because of its small size (only 15 patients) [11,53,100]. A recent French study analyzed correlations between iron biomarkers (ferritin, iron, transferrin, TSAT, erythrocyte mean corpuscular volume and hepcidin) and liver iron concentrations measured blindly by quantitative MRI, and examined their accuracy for the diagnosis of iron overload in a prospective cohort of 212 hemodialysis patients treated with parenteral iron-sucrose and ESA, in keeping with ERBP anemia statements [18,81].…”

“…Likewise, in logistic analysis, only serum ferritin correctly classified the patients into those with normal liver iron stores (LIC 50 mmol/g) and those with elevated liver iron stores (LIC > 50 mmol/g) (odds ratio 1.007; 95% CI: 1.004-1.010) [100]. Serum ferritin was the most discriminatory iron biomarker in ROC curve analysis (AUC = 0.767; 95% CI: 0.698-0.835) as compared to hepcidin (AUC = 0.710; 95% CI: 0.631-0.789), transferrin (AUC = 0.703; 95% CI: 0.623-0.783) and TSAT (AUC = 0.634; 95% CI: 0.552-0.715).…”

“…Recent MRI studies of LIC in hemodialysis patients have attempted to find a correlation between iron biomarkers and the liver iron concentration, and to define thresholds of risk of iron overload based on these biomarkers [11,53,100]. Ferritin correlated with LIC in both the Italian and French studies, but not in the Australian study because of its small size (only 15 patients) [11,53,100].…”

“…A recent French study analyzed correlations between iron biomarkers (ferritin, iron, transferrin, TSAT, erythrocyte mean corpuscular volume and hepcidin) and liver iron concentrations measured blindly by quantitative MRI, and examined their accuracy for the diagnosis of iron overload in a prospective cohort of 212 hemodialysis patients treated with parenteral iron-sucrose and ESA, in keeping with ERBP anemia statements [18,81]. The relationships were analysed using Spearman's coefficient, logistic regression, and ROC curves [100]. Serum ferritin showed the strongest correlation with LIC (rho = 0.52).…”

“…Serum ferritin was the most discriminatory iron biomarker in ROC curve analysis (AUC = 0.767; 95% CI: 0.698-0.835) as compared to hepcidin (AUC = 0.710; 95% CI: 0.631-0.789), transferrin (AUC = 0.703; 95% CI: 0.623-0.783) and TSAT (AUC = 0.634; 95% CI: 0.552-0.715). The optimal serum ferritin cut offs were 160 mg/L for LIC > 50 mmol/g (mild and moderate overload; diagnosis accuracy 69.30%; specificity 76.9%; sensitivity 66.9%) and 290 mg/L for LIC > 200 mmol/g (severe overload; diagnosis accuracy 75.9%; specificity 77%; sensitivity 72.3%) [100]. This latter ferritin cut off is close to that found in the Italian study performed by SQUID (340 mg/L); differences in the accuracy of LIC measurement between SQUID and MRI and on the size of the populations studied may explain these discrepancies [11,100].…”