Low levels of serum ferritin and moderate transferrin saturation lead to adequate hemoglobin levels in hemodialysis patients, retrospective observational study

Abstract

BackgroundOptimal iron levels in patients on hemodialysis are currently unknown, and a higher level than that for the healthy population is usually set for such patients considering the use of erythropoiesis-stimulating agents or the occurrence of chronic inflammation. However, excessive iron causes oxidative stress and impairment of its utilization by cells. Therefore we investigated the relationship between hemoglobin (Hb) level and iron status in hemodialysis patients to identify the optimal iron levels for patients undergoing hemodialysis.MethodsA total of 208 outpatients on maintenance hemodialysis were followed up between July 2006 and June 2007. Men accounted for 64.9% cases [mean age, 59.3 ± 13.1 years and median dialysis history, 7.7 (3.6–13.2) years], and diabetic nephropathy accounted for 25.0% cases. Hemoglobin level was measured twice a month and serum ferritin, serum iron, and total iron-binding capacity were measured once a month. The doses of recombinant human erythropoietin and low-dose iron supplement were adjusted to maintain a hemoglobin level of 10–11 g/dL, according to the guidelines of the Japanese Society for Dialysis Therapy. Hepcidin was measured at baseline. Using the mean values for 1-year period, the relationships among hemoglobin, serum ferritin levels, and transferrin saturation levels were investigated based on a receiver operating characteristic curve and a logistic regression model. In addition, the correlations among serum ferritin, transferrin saturation, and hepcidin levels were analyzed by Pearson product—moment correlation coefficient and linear regression model.ResultsBy receiver operating characteristic curve, the cutoff point of serum ferritin and transferrin saturation levels with a hemoglobin ≥10 g/dL showed <90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001) and ≥20% (sensitivity: 77.6%, specificity: 48.8%, p = 0.302).Upon logistic regression model analysis with a hemoglobin ≥10 g/dL as the endpoint, the analysis of odds ratios relative to a group with serum ferritin ≥90 ng/mL and transferrin saturation <20% revealed that the group with serum ferritin <90 ng/mL and transferrin saturation ≥20% had the highest ratio: 46.75 (95% confidence interval: 10.89–200.70, p < 0.001). In Pearson product—moment correlation coefficient, hepcidin showed a strong positive correlation with serum ferritin [r = 0.78 (95% confidence interval: 0.72–0.83, p < 0.001)] and a weak positive correlation with transferrin saturation [r = 0.18 (95% confidence interval: 0.04–0.31, p = 0.010)]. In the multivariable analyses of the linear regression model, a positive relationship was shown between hepcidin and serum ferritin [β-coefficient of 0.30 (95% confidence interval: 0.27–0.34, p < 0.001)]; however, no relationship was shown with transferrin saturation [β-coefficient of 0.09 (95% confidence interval: −0.31–0.49, p = 0.660)].ConclusionsIn this study, the iron status of serum ferritin <90 ng/mL and transferrin saturation ≥20% was optimal in hemodialysis patients receiving recombinant huma...

Effect of Sucroferric Oxyhydroxide on Fibroblast Growth Factor 23 Levels in Hemodialysis Patients

“…The hepcidin and ferritin levels in the control group increased with increasing doses of intravenous saccharated ferric oxide. There have been reports of a positive correlation between serum ferritin and hepcidin levels and an increase in serum ferritin and hepcidin levels in association with inflammation [28,29]. However, there were no significant changes in C-reactive protein levels in the present study.…”

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

“…It combined quantitative MRI (Rennes signal‐intensity ratio) with data‐mining and classical statistical analysis, in 212 hemodialysis patients free of overt inflammation and malnutrition (and treated for anemia per current guidelines) to identify the accurate target values for biological markers of iron metabolism. Among the biological markers, only serum ferritin showed a strong correlation with LIC and logistical analyses correctly classified patients as having normal liver iron stores (LIC ≤ 50 μmol/g) or elevated stores (LIC > 50 μmol/g) . Serum ferritin was the iron biomarker with the best discriminatory capacity in ROC curve analysis (AUC: 0.77); the optimal serum ferritin cutoff was 162 μg/L for LIC > 50 μmol/g (mild iron overload; sensitivity 67%; specificity 77%; diagnostic accuracy 69%) .…”

“…Among the biological markers, only serum ferritin showed a strong correlation with LIC and logistical analyses correctly classified patients as having normal liver iron stores (LIC ≤ 50 lmol/g) or elevated stores (LIC > 50 lmol/g). 60 Serum ferritin was the iron biomarker with the best discriminatory capacity in ROC curve analysis (AUC: 0.77); the optimal serum ferritin cutoff was 162 lg/L for LIC > 50 lmol/g (mild iron overload; sensitivity 67%; specificity 77%; diagnostic accuracy 69%). 61 Thus, an upper target of 150 lg/L ferritin in HCV-ESRD patients would greatly minimize the risk of increased liver iron load with potential harmful consequences.…”

“…The Japanese Society for Dialysis, out of concern for iron overload, proposed as early as 2011 that minimal IV iron (up to 650 mg in the induction phase) be given to hemodialysis patients and only in cases of true iron deficiency (ferritin < 100 μg/L), and also warned against maintenance IV iron therapy . This careful strategy of iron repletion allowed adequate hemoglobin levels with low ferritin, moderate transferrin saturation without any detrimental effect on survival and was again advocated this year for Japanese dialysis populations …”

“…57 This careful strategy of iron repletion allowed adequate hemoglobin levels with low ferritin, moderate transferrin saturation without any detrimental effect on survival and was again advocated this year for Japanese dialysis populations. [58][59][60] Taking into account the lower body surface area of Japanese patients, the proposed dose of iron for repletion (600 mg) should be adapted to around 800 mg in European patients and 1000 mg in US patients. 38 A recent French study designed to determine the accuracy of biomarkers of iron metabolism in dialysis patients on parenteral iron therapy may offer physicians further insight.…”