Functional Iron Deficiency In Patients Research Articles

Potential Association of Serum Hepcidin, hs-CRP and Iron Status Levels in Hemodialytic Patients

Patients on hemodialysis (HD) are usually anemic because of defective erythropoiesis. Hepcidin is a polypeptide that regulates iron homeostasis and could indicate functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in assessing a patient's response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status, and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. Forty-two patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 age and sex-matched healthy subjects were included as controls. Laboratory tests were performed, including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron, and CRP. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 \(\pm\) 2.8 ng/mL and 8.5 \(\pm\) 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC, and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 (\pm) 2.4 ng/mL), while lower levels (16.9 \(\pm\) 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases and EPO resistance.

Serum hepcidin levels as indicator of anemia status in male hemodialysis patients

Background: Hepcidin is a polypeptide hormone as regulator of iron homeostasis, and it plays an important role of functional iron deficiency in patients with chronic kidney disease (CKD) which associated with hemodialysis (HD) because of defective erythropoiesis in CKD. This study was conducted to assess the association between hepcidin and anemia status in HD patients. This was a cross-sectional study of 65 HD patients and EPO therapy were enrolled; compared with 25 age matched healthy individuals as controls. The current study was investigated serum hepcidin, iron status was included serum ferritin and iron levels, anemia hematological indices such as RBC, Hb, MCV, and MCH, in addition to other clinical parameters of kidney function, and C-reactive protein (CRP) as inflammation markers were performed in both HD patients and controls. Results: The mean patient age was (45.65±13.34) years, with dialysis vintage of median (IQR) was (12 (3-36) month. serum hepcidin were highly significantly increase in HD patients than in the control group (622.3±139.6, and 465.16±80.31pg/ml, respectively p = 0.0001). serum hepcidin significantly associated with 37% anemia severity about (692.4±119.8) pg/ml more than patient with 49.2% of moderate about (605.3±117.7) pg/ml, (p=0.007) as compared with 13.8% of mild anemia groups (531.8±99.12) pg/ml, (p=0.001).

Compensating functional iron deficiency in patients with allergies with targeted micronutrition

SummaryIron deficiency is associated with atopy. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both allergic children and adults are more likely to have iron deficiency anemia. Immunologically, iron deficiency leads to activation of antigen-presenting cells, promotion of Th2 cells and enables antibody class switch in B cells. In addition, iron deficiency primes mast cells for degranulation, while an increase in their iron content inhibits their degranulation. Many allergens, especially those with lipocalin and lipocalin-like protein structures, are able to bind iron and either deprive or supply this trace element to immune cells. Thus, a local induced iron deficiency will result in immune activation and allergic sensitization. However, lipocalin proteins such as the whey protein β‑lactoglobulin (BLG) can also transport micronutrients into the defense cells (holo-BLG: BLG with micronutrients) and hinder their activation, thereby promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holo-BLG as a supplementary balanced diet, leading to a reduction in symptom burden. Supplementation with holo-BLG specifically supplied defense cells with micronutrients such as iron and therefore represents a new dietary approach to compensate for functional iron deficiency in allergy sufferers.

Zinc Protoporphyrin Is a Reliable Marker of Functional Iron Deficiency in Patients with Inflammatory Bowel Disease.

Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%); fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC; 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.

THE ASSOCIATION BETWEEN LEVELS OF HEPCIDIN, IRON STATUS AND MICRO-INFLAMMATION MARKERS AMONG HAEMODIALYSIS

Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient's response to erythropoietin (EPO). Erythropoietin is a cytokine glycoprotein secreted by the kidney in response to cellular hypoxia; it stimulates the production of red blood cells (erythrocytes) in the bone marrow. The present study was aimed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 59 patients on maintenance HD were enrolled; 29 age and sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, creatinine, urea, albumin, BUN, serum hepcidin, serum ferritin, serum iron and CRP were performed. The serum hepcidin levels was measured by a competitive enzyme-linked immunosorbent assay (C-ELISA). Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (63.7±47.4 ng/mL: 11.5± 26.3 ng/mL respectively P<0.001). The hemoglobin and serum iron levels in the patient group were significantly lower than in the control group. Higher feritine levels were found in hemodialysis patients (448.5±710 ng/mL): ( 98.3±83 ng/mL) of controls (P =0.01). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Serum hepcidin and high-sensitivity C-reactive protein levels were significantly higher in maintenance haemodialysis patients (case=21.2±28.6 mg/L:control=2.9±2.7 mg/L, P=0.001). In conclusion, higher hepcidin levels are found in ESRD patients and serum hepcidin levels are associated with iron status and micro-inflammation (defined as hsCRP < 6mg/l, in maintenance haemodialysis patients). Also, our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as ESRD. As well as, ELISA method for measuring serum hepcidin should facilitate the routine measurement of hepcidin in clinical practice.
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Assessment of iron-restricted erythropoiesis in chronic renal disease: evaluation of Abbott CELL-DYN Sapphire mean reticulocyte hemoglobin content (MCHr)

We studied the performance of mean reticulocyte hemoglobin content (MCHr), measured on Abbott CELL-DYN Sapphire analyzer for the detection of functional iron deficiency. Patients with anemia and with renal disease were prospectively selected from the outpatient population of our hospital, 512 subjects were studied. Diagnoses and other medical data were retrieved from the hospital information system. MCHr was measured using a CELL-DYN Sapphire hematology analyzer (Abbott Diagnostics). Standard laboratory and statistical tests were used. Receiver operating characteristic (ROC) analysis was used to establish the diagnostic performance of MCHr for detecting iron-restricted erythropoiesis, with transferrin saturation <20% as the gold standard. Patients in the iron deficiency anemia group all had a state of iron depletion and iron-restricted erythropoiesis (median MCHr 25.4 pg). Patients with anemia of chronic disease showed also low MCHr, median 27.6 pg, but not statistically different from the iron deficient group (p = .0585). Renal patients with iron restriction (n = 66) had significantly lower MCHr (p < .0001) than those receiving adequate iron supply (n = 100): median MCHr were 27.9 and 32.5 pg, respectively. ROC analysis gave sensitivity 84.4% and specificity 80.1% with area under curve 0.863 (95% CI 0.823–0.902) at an MCHr cut-off 30.0 pg. MCHr on CELL-DYN Sapphire has equivalent clinical performance for detecting absolute or functional iron deficiency in patients with chronic kidney disease as previously published for another type of analyzer.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation

Introduction:Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID.Objectives:This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition.Statistical analysis:The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student’s t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05.Results:Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05).Discussion:FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

The importance of iron metabolism, hepcidine and soluble transferrin receptor in pathogenesis of anemia in patients with solid tumors

A comparative analysis of hemogram parameters, iron metabolism, C-reactive protein, hepcidin, soluble transferrin receptor in patients with malignant neoplasms, accompanied by anaemia and without it. Patients with anaemia compared with non-anaemic patients had lower haemoglobin, erythrocyte, hematocrit, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration, iron, iron transferrin saturation, total iron-binding capacity, and higher levels C-reactive protein, hepcidin, soluble transferrin receptor (p0,05). Negative correlations of moderate strength between hepcidin and erythrocyte levels (r=-0,41), hemoglobin (r=-0,3), hematocrit (r=-0,35), and total iron-binding capacity (r=-0,51) and transferrin (r=-0,54). In addition, negative correlations of moderate strength were revealed between the soluble transferrin receptor and hemoglobin level (r=-0,57), hematocrit (r -0,49), iron transferrin saturation (r=-0,47), mean corpuscular hemoglobin (r=-0,44), mean corpuscular volume (r=-0,39). A direct correlation of moderate strength was found between the soluble transferrin receptor and transferrin (r=0,41) and total iron-binding capacity (r=0,38), as well as between hepcidin and ferritin (r=0,61), C-reactive protein (r=0,48). In general, the development of functional iron deficiency in patients with anaemia and malignant neoplasms has been established, and the value of hepcidin and soluble transferrin receptor in the genesis of this anaemia has been confirmed.

FUNCTIONAL IRON DEFICIENCY ANAEMIA IN CHRONIC KIDNEY DISEASE PATIENTS

Introduction: Anemia is one of the major harms in hemodialysis patients, which is caused by inadequate production of erythropoietin. Functional iron deficiency (FID) anemia is a type of anemia, characterized by lack of functional iron. There are many markers identified for assessing FID in patients of chronic kidney disease(CKD). Of these the most sensitive marker is percentage of hypo chromic red cells (%HRC).&#x0D; Objective: To observe the frequency of functional iron deficiency in patients of chronic kidney diseases by percentage of hypo chromic red cells.&#x0D; Methodology: This study was carried out in the Ibnae –Sienna Hospital Multan from March 2016 to September 2016. All those CKD patients who were on hemodialysis and on erythropoietin stimulating agent (ESA) were included in the study. However, those patients who had history of chronic infections like tuberculosis or any history of malignancy were not included in this study. For this study, 150 patients on hemodialysis and on ESA were recruited. Hemoglobin (Hb), mean cell volume (MCV) and %Hypo were measured on the Sysmex XE 5000.&#x0D; Results: A sum of 150 hemodialysis patients on ESA were enrolled in this study. Of these 57.3%were males while 42.7% were females. The average age of patients was 48.71±11.92 years. Functional iron deficiency was observed in 28.7% of patients on hemodialysis.&#x0D; Conclusion: Percentage of hypochromic red cells (%HRC) is the most sensitive marker for diagnosis of FID. Timely diagnosis will help in reducing treatment related complications and improve quality of life.

Pathogenetic Characteristics of Anemia in Patients with Solid Tumors

Aim. To study the impact iron metabolism disturbances and cytokine levels on the development of anemia in patients with solid tumors. Materials &amp; Methods. The research included 42 patients with malignant neoplasms, including 24 patients with anemia (19 men and 5 women, median age 67.7 ± 10 years) and 18 patients without anemia (15 men, 3 women, median age 65.7 ± 14 years). Anemia was diagnosed according to the WHO criteria (in men: erythrocytes &lt; 4.0 &lt;sup&gt;x&lt;/sup&gt; 10&lt;sup&gt;12&lt;/sup&gt;/L, hemoglobin &lt; 130 g/L, hematocrit &lt; 39 %; in women: erythrocytes &lt; 3.8 &lt;sup&gt;x&lt;/sup&gt; 10&lt;sup&gt;12&lt;/sup&gt;/L, hemoglobin &lt; 120 g/L, hematocrit &lt; 36 %). Results. A comparative analysis of iron metabolism in patients with and without anemia was performed. The lower values of serum iron and transferrin saturation in patients with anemia were shown (p &lt; 0.05). The total iron-binding capacity, the levels of ferritin, transferrin, C-reactive protein, indirect bilirubin were similar between groups (p &gt; 0,05). Higher levels of interleukins 6 and 10 (IL-6 and IL-10) were observed in patients with anemia (p &lt; 0.05). For IL-6, correlations were observed with levels of erythrocytes (r = -0,58), hemoglobin (r = -0,57), hematocrit (r = -0,52), and leukocytes (r = 0,42). The levels of IL-10 slightly correlated with the levels of erythrocytes, leukocytes, platelets, MCV, and MCH (r &lt; 0.3). For IL-10, correlations were established with levels of MCHC (r = -0,71), hemoglobin (r = -0,64) and hematocrit (r = -0,32). Correlations between the levels IL-6, IL-6 and hemoglobin, erythrocytes and several color indices may indicate their influence on the development of anemia in patients with malignant neoplasms. Conclusion. A functional iron deficiency in patients with anemia was found. Several causes of anemia development and significant role of interleukins in anemia pathogenesis were also discovered.

Differential diagnosis of anemia in true and functional iron deficiency in patients with chronic diseases (malignant tumors)

To make a differential diagnosis of true and functional iron deficiency (ID) in anemia of chronic diseases (ACD). A total of 540 patients (785 investigations) and 311 healthy individuals (a control group) were examined. Among them, there were 118 cancer patients admitted for surgical treatment and 226 for chemotherapy (CT), 56 blood cancer patients, 86 with breast diseases without anemia, and 54 workers of the institute with the signs of ID. An enzyme immunoassay was used to determine the plasma levels of ferritin (FR), soluble transferrin receptor (sTFR), and endogenous erythropoietin (EPO). 183 cancer patients did not receive specific treatment, 161 had different cycles of CT. In true ID, anemia was microcytic (average red blood cell size, <80.0 fl) and hypochromic (mean corpuscular hemoglobin concentration, <27.0 pg) with low FR levels (less than 20 ng/ml) and high sTFR concentrations (more than 4.0 µg/ml). The EPO level corresponded to the degree of anemia and was 4-5-fold the normal values. In ACDs, 292 (55%) patients had normocytic normochromic anemia with high FR levels (more than 100 ng/ml), the level of sTFR was low and that of EPO did not correspond to the degree of anemia in 74% of the patients. Functional ID was detected in 108 (37%) cancer patients in the presence of ACD. Despite high FR levels and low sTFR, anemia in Hodgkin's and non-Hodgkin's lymphomas was hypochromic microcytic, which may be considered as severe functional ID in ACD. In addition to a clinical blood test, the pharmacokinetic parameters (FR, sRFR, and EPO) should be determined for the differential diagnosis of true and functional ID.

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation

BackgroundAnemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. MethodsIron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. ResultsAbsolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. ConclusionsBoth absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation.

Assessment of human iron status: A cross-sectional study comparing the clinical utility of different laboratory biomarkers and definitions of iron deficiency in daily practice

ObjectivesNo full international consensus exists on disease markers to be used for assessing the human iron status. Therefore this study was conducted to compare performances of serum ferritin and transferrin saturation (TSAT) versus soluble transferrin receptor (sTfR)/log ferritin and reticulocyte hemoglobin content (CHr), also known as Thomas-plot, in the diagnosis of iron deficiency (ID). Design and methodsA total of 445 consecutive hospitalized patients, referred for routine testing of the actual iron status, were included. Logistic regression models for the probability of functional ID (CHr<28pg) were constructed for all 445 patients, for 225 patients without (C-reactive protein [CRP]≤0.5mg/dL) and 220 patients with acute-phase reaction (CRP>0.5mg/dL). ResultsBased on the Thomas-plot analyses, 153/445 (34.38%) patients were identified with ID. When ID was diagnosed by means of serum ferritin levels<30ng/mL and TSAT levels<20%, 105/445 (23.60%) and 215/445 (48.31%) patients were identified with ID, respectively. The sTfR/log ferritin ratio showed the best positive predictive values (PPV) (62.50 and 64.41%) to indicate functional ID in patients without as well as with acute-phase reaction compared to sTfR (58.14 and 61.67%), ferritin (32.50 and 32.86%) and TSAT (26.74 and 42.86%). ConclusionsIn clinical practice, the prevalence of ID and the accuracy to detect functional ID are dependent on marker selection and its definition. Regarding the results of this work, for laboratory investigation of ID, however, we suggest using Thomas-plot analyses in combination with ferritin single-marker measurements to efficiently identify patients with ID.

Hepcidin-25 vs. conventional clinical biomarkers in the diagnosis of functional iron deficiency.

As hepcidin-25 is considered as a key regulator of human iron homoeostasis, this study aimed to compare this parameter with conventional biomarkers and diagnostic tools of iron deficiency (ID). In total, 233 hospitalised adult patients, who underwent routine blood testing for ID, were included. All subjects were investigated for hepcidin-25, reticulocyte haemoglobin content (CHr), soluble transferrin receptor (sTfR)/log ferritin ratio (i.e. Thomas plot), sTfR, ferritin, transferrin saturation (TSAT), C-reactive protein (CRP) and for complete blood cell count. Functional ID was defined as a CHr<28pg. Separate logistic regression models were calculated with all potential biomarkers to evaluate and compare the predictive performance with respect to functional ID in patients without (CRP≤0.5mg/dL) and with (CRP>0.5mg/dL) acute-phase reaction, respectively. One hundred seventeen patients with CRP>0.5mg/dL showed a distinctly higher hepcidin-25 median value [35.60 (range: 4.27-80.03) ng/mL] as compared to 116 patients with CRP≤0.5mg/dL [18.55 (range: 3.77-73.01) ng/mL]. With respect to functional ID, sTfR/log ferritin ratio and sTfR were of better positive predictive value (PPV) (sTfR/log ferritin ratio: 58.33% and 70.83%; sTfR: 60.00% and 60.00%) than when compared to hepcidin-25 (PPV: 37.74% and 42.86%) and ferritin (PPV: 27.54% and 46.15%) in both subgroups. The sTfR/log ferritin ratio, as well as sTfR, were better predictors of functional ID in patients with and without acute-phase reaction as compared to hepcidin-25 and ferritin.

Serum hepcidin levels in patients with end-stage renal disease on hemodialysis.

Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient's response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 42 patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 ageand sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron and CRP were performed. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 ± 2.8 ng/mL and 8.5 ± 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 ± 2.4 ng/mL) while lower levels (16.9 ± 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as well as EPO resistance.

Double bull's eye for post-operative intravenous iron in patient blood management: better outcome and cost-effective.

Double bull's eye for post-operative intravenous iron in patient blood management: better outcome and cost-effective.

Intravenous Ferric Carboxymaltose As Sole Anemia Therapy In Patients With Lymphoid Malignancies, Chemotherapy-Induced Anemia and Functional Iron Deficiency

IntroductionFor patients with chemotherapy-induced anemia (CIA) and functional iron deficiency (FID) who are treated with an erythropoiesis-stimulating agent (ESA), guidelines recommend intravenous (IV) iron supplementation and resolution of iron deficiency (ID) before ESA use to reduce blood transfusions and ESA doses (both linked to safety concerns). This prospective, randomized phase II study evaluated ferric carboxymaltose (FCM, Vifor Pharma) without additional ESA for correction of anemia and FID in patients with lymphoid malignancies receiving antineoplastic therapy. Patients and MethodsPatients with indolent lymphoid malignancies (non-Hodgkin lymphoma, multiple myeloma or chronic lymphocytic leukemia), anemia (Hb 8.5-10.5 g/dL) and FID (transferrin saturation [TSAT] ≤20% and stainable bone marrow iron or serum ferritin >30 ng/mL [women] to >40 ng/mL [men]), who had been on chemotherapy (CT) for at least 8 weeks or two cycles were randomized to FCM (1000 mg iron) or no anemia treatment (control). Iron was administered within 24 hours before or after the next chemotherapy cycle's first treatment. The primary endpoint was the mean Hb change from baseline to Weeks 4, 6 and 8 without use of blood transfusions or ESA. Secondary endpoints included Hb response (increase ≥1.0 g/dL) or Hb correction (Hb ≥11.0 g/dL) at any week and changes in hematologic variables, endogenous erythropoietin (EPO), hepcidin and interleukin (IL)-6 over time. Data are shown as median [range]. Enrollment was stopped after 19 of planned 40 patients due to low recruitment. ResultsOf 19 randomized patients, 17 (8 FCM, 9 control; 11 males, age 71 y [26-88 y]) were analyzed for the primary endpoint (full analysis set, FAS). FCM-treated patients had a significant Hb increase vs. baseline at any week (Table). Mean Hb increase at Week 8 was significantly higher in the FCM than the control group (FAS, Fig. A, Table). In the per protocol population (PPS; 5 FCM, 7 control), mean Hb increase in the FCM group was significantly higher from Week 4 onwards (Fig. B). All FCM-treated patients in the FAS achieved Hb response (time to response 2.3 [0.6-6.0] weeks) compared to only 6 of 9 (66.7%) control patients (time to response 4.4 weeks). Hb was corrected in 87.5% (7 of 8) FCM-treated and 55.6% (5 of 9) control patients. In the FCM group, median Hb was >11.0 g/dL from Week 6 and TSAT was >20% from Week 2 onwards, whereas in the control group, none exceeded these cut-offs. EPO, hepcidin and IL-6 levels did not show any significant variations (Table). No blood transfusion or ESA treatment was given in either group, and no treatment-related adverse events (AEs) were recorded during the study. Five (62.5%) patients in the FCM and one (9.1%) in the control group reported 12 and 2 unrelated AEs, respectively, in this open-label study. All AEs except one unrelated, fatal post-study injury were mild or moderate. [Display omitted] [Display omitted] ConclusionThis pilot study indicates that ferric carboxymaltose without additional ESA may effectively increase and correct Hb levels and is well tolerated in patients with lymphoid malignancies, CIA and FID. Hb improvement is supported by resolution of ID from the first post-treatment visit onwards. A larger phase 3 study in a representative patient population is warranted to confirm the results of this study. Disclosures:Hedenus:Vifor Pharma: Consultancy, Honoraria. Ludwig:Vifor Pharma: Honoraria. Felder:Vifor Pharma: Employment. Roubert:Vifor Pharma: Employment. Birgegard:Vifor Pharma: Honoraria.

Comparative Study of Intravenous Iron Versus Intravenous Ascorbic Acid for Treatment of Functional Iron Deficiency in Patients Under Hemodialysis. A Randomized Clinical Trial

BackgroundFunctional iron deficiency (FID) may cause erythropoietin resistance in patients under hemodialysis (HD). Since the role of chronic inflammation or oxidative stress in its pathogenesis is unclear, controversy remains to whether intravenous iron or intravenous ascorbic acid (an antioxidant) can improve this anemia due to decreased iron availability.ObjectivesThe current study compared the effect of intravenous iron versus intravenous ascorbic acid in the management of FID in HD patients.Patients and MethodsForty HD patients with hemoglobin (Hb) ≤ 11 g/dL, serum ferritin ≥ 500 ng/mL and transferrin saturation (TSAT) ≤ 25% were randomly divided into two groups. 20 patients received 100 mg of intravenous (IV) iron (group I), and 20 patients received 300 mg of IV ascorbic acid (group II) postdialysis, twice a week for 5 consecutive weeks. Hb and iron metabolism indices were measured before the onset of the study and after 12 weeks following therapy.ResultsTwenty one percent of all HD patients, exhibited high serum ferritin, low TSAT and sufficient data for analysis. Both Group I (n = 20) and Group II (n = 20) patients showed a significant increase in Hb, serum iron, and TSAT (P < 0.001). There were no significant differences between both groups in increasing Hb (P = 0.076), serum iron (P = 0.589), serum ferritin (0.725), and TSAT (P = 0.887).ConclusionsThis study showed that both IV iron and IV ascorbic acid can improve FID in HD patients. A larger randomized trial is warranted to determine the optimal management of FID in HD patients.

New parameters in iron metabolism and functional iron deficiency in patients on maintenance hemodialysis

Iron metabolism has been studied for many years. New substances involved in iron metabolism continue to be described. Functional iron deficiency (FID) is characterized by the presence of adequate iron stores (as defined by standard criteria) but insufficient iron mobilization required for erythropoiesis during administration of erythropoiesis-stimulating agents. The aim of the study was to evaluate new parameters of iron metabolism and the prevalence of FID as well as to assess potential correlations in patients on hemodialysis (HD). The study included 98 patients on maintenance HD. Standard laboratory methods were used to measure the iron status, complete blood count, creatinine, calcium, phosphorus, albumin, intact parathyroid hormone, and lipids. Commercially available kits were used to measure high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor-α, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF15), bone morphogeneticprotein (BMP6), hemojuvelin, and hepcidin. FID was present in 23% of the patients on HD and was associated with significantly higher serum ferritin, IL-6, hsCRP, hepcidin, and NT-proBNP levels. There were no significant differences in BMP6 and GDF15 levels between patients with and without FID. Patients on HD had increased prevalence of hypertension, diabetes, and left ventricular hypertrophy and required slightly, but insignificantly, higher erythropoietin doses. Predictors of FID included serum iron levels and residual renal function. FID is present in a substantial proportion of patients on HD, who thus should be screened for reversible causes of inflammation. New parameters in iron metabolism do not seem to be related to FID in patients on HD.

Indices of iron status in patients treated by chronic haemodialysis.

Iron deficiency in patients with end stage renal disease (ESRD) treated by haemodialysis (HD) is difficult to diagnose. The reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red cells (%hypo) are sensitive novel assays for the detection of functional iron deficiency in patients treated with erithropoietin (EPO). In our study thirty-nine chronically hemodialyzed patients were evaluated to determine the value of these two parameters in comparison to the conventional biochemical indicators of iron metabolism. There were significant correlations between CHr and transferrin saturation, CHr and weekly dosage of EPO, and also between %hypo and weekly dosage of EPO. Our data represent superior value of %hypo and CHr to the transferrin saturation and ferritin concentration in detecteng of iron deficiency in HD patients.