Hepcidin-25, Mean Corpuscular Volume, and Ferritin as Predictors of Response to Oral Iron Supplementation in Hemodialysis Patients

Takasawa, Kazuya; Takaeda, Chikako; Maeda, Teiryo; Ueda, Norishi

doi:10.3390/nu7010103

Cited by 17 publications

(24 citation statements)

References 44 publications

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“…At all time points there was a clear and significant correlation between serum hepcidin level and ferritin level. This is consistent with published data in hemodialysis patients [ 5 , 6 , 15 , 18 , 19 , 27 ] and, as in our population, non-dialysis dependent patients with CKD [ 5 , 20 ]. The utility of hepcidin as a marker for iron stores is limited, however, due to the high intra-individual variation in hepcidin levels [ 13 ].…”

Section: Discussionsupporting

confidence: 94%

“…As with ferritin, however, the predictive value of hepcidin is complicated by the influence of inflammation on hepcidin levels [ 3 , 12 ], and by high intra-individual variation [ 13 ]. Data are conflicting regarding an association between hepcidin and the erythropoietic response to erythropoiesis stimulating agent (ESA) therapy [ 13 – 17 ], or iron therapy [ 13 , 16 , 18 – 22 ]. The longitudinal response of hepcidin levels to iron therapy has not been examined, nor are there any data comparing the short- or long-term hepcidin response to intravenous (IV) versus oral iron therapy.…”

Section: Introductionmentioning

confidence: 99%

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Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial

Gaillard

Böck

Carrera³

et al. 2016

PLoS ONE

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Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400–600μg/L) or lower (100–200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial

Gaillard

Böck

Carrera³

et al. 2016

PLoS ONE

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“…Furthermore, anemia correction effects for oral iron administration were poor in the groups with mean values of s-ft and hepcidin in the range of 30 ng/mL on HD patients [33]. These studies indicate that s-ft does not need to be maintained at a level as high level as that previously considered and that iron deficiency affects hematopoiesis only mildly if s-ft > 30 ng/mL and hepcidin > 20–30 ng/mL are maintained.…”

Section: Discussionmentioning

confidence: 99%

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

Ogawa¹,

Tsuchiya²,

Tomosugi

et al. 2017

PLoS ONE

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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...

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“…Table (3), figure (4). [12], [13] Hepcidin may play a significant role in the pathogenesis of chronic kidney disease (CKD) complications associated with disturbed iron metabolism.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Role of Hepcidin in Predicting the Therapeutic Efficacy of Erythropoiesis-Stimulating Agent Treatment in Patients of Chronic Renal Failure

El-HadyAhmed

El-Maghraby

2016

Zagazig University Medical Journal

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Background: Chronic kidney disease is associated with increase serum hepcidin level which contributes to severity of anemia and to resistance of erythropoiesis stimulating agents and dysregulation of iron hemostasis. Serum hepcidin correlates positively with ferritin in patients on hemodialysis. Subjects and Methods: fifty patients of end stage renal disease(ESRD) on regular hemodialysis and on erythropoietin therapy, twenty seven males, twenty three females and twenty subjects as control. Group matched for age, gender were clinically assessed and laboratory investigations were done in the form of serum urea, creatinine, iron profile (serum iron, ferritin, total iron binding capacity), serum erythropoietin, serum hepcidin, and hemoglobin. Results: There is significant negative correlation between hepcidin and hemoglobin, iron, total iron binding capacity and erythropoietin (P<0.01) and positive significant correlation between serum hepcidin and serum ferritin (P<0.05) in both male and female groups. Hepcidin and serum ferritin are higher in patients groups than control but erythropoietin is lower in patients groups than control with statistical significance (P<0.01).

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Hepcidin-25, Mean Corpuscular Volume, and Ferritin as Predictors of Response to Oral Iron Supplementation in Hemodialysis Patients

Cited by 17 publications

References 44 publications

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial

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

Evaluation of the Role of Hepcidin in Predicting the Therapeutic Efficacy of Erythropoiesis-Stimulating Agent Treatment in Patients of Chronic Renal Failure

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