Functional Iron Deficiency Research Articles

Role of Hepcidin in Anemia of Chronic Disease in Rheumatoid Arthritis.

Objective Anemia of chronic disease is a frequent consequence in rheumatoid arthritis and is associated with major clinical and patient outcomes. The present cross-sectional study explored the role of hepcidin (HEP) in anemia of chronic disease in rheumatoid arthritis by studying its relationships with markers of anemia, iron metabolism, inflammation, and erythropoiesis. Methods Blood samples from anemic ( n = 43) and nonanemic ( n = 43) rheumatoid arthritis patients were analyzed for markers of anemia (hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cells distribution width, and reticulocyte hemoglobin), iron metabolism (iron, total iron binding capacity, ferritin, transferrin saturation, soluble transferrin receptor), inflammation (erythrocyte sedimentation rate, C-reactive protein, and interleukin 6), and erythropoiesis (erythropoietin and HEP). Correlation analysis was used to identify relationships between HEP and all other variables. Principal component analysis was used to identify common underlying dimensions representing linear combinations of all variables. Results HEP had statistically significant mostly moderate-to-large correlations with markers of anemia (0.30–0.70, all p < 0.01), small correlation with markers of iron metabolism and markers of inflammation ( r = 0.20–0.40, all p < 0.01), and moderate correlations with markers of erythropoiesis. Principal component analysis revealed two underlying components (factors) capturing approximately 50% of total variability. Factor 1 comprised mainly of markers of anemia, iron metabolism, and erythropoiesis and was related to “erythrocyte health status,” while factor 2 comprised mainly markers of inflammation and iron metabolism and was related to “acute phase reactants.” HEP was the only variable demonstrating substantial loadings on both factors. Conclusions HEP is related to markers of anemia, iron metabolism, inflammation, and erythropoiesis. In addition, when all variables are “reduced” to a minimum number of two “latent” factors, HEP is loaded on both, thus underlying its pivotal role in the complex interaction of the erythropoietic response in inflammation-induced anemia and/or functional iron deficiency.

DIAGNOSTICS AND TREATMENT OF ANEMIC SYNDROME IN PATIENTS WITH BREAST CANCER ON THE BACKGROUND OF NEOADJUVANT CHEMOTHERAPY

Introduction. In recent years, a separate publications have appeared indicating that interleukin 6 (IL-6) and the protein hepcidin 25 (GP25) play a significant role for the development of functional iron deficiency (FID) in oncological patients with a widespread tumor process. It is important to differentiate between FID and iron deficiency anemia (IDA), since they have the same morphological characteristics, but their treatment is fundamentally different.The aim of this study was to study the main metabolites of ferrokinetics, IL-6 and C-reactive protein (CRP) expression parameters in patients with breast cancer on the background of neoadjuvant chemotherapy to develop individual approaches to the diagnosis and treatment of anemic syndrome (AS), prediction, early detection of anemia and its adequate correction.Materials and methods. The study was conducted in 31 breast cancer patients, during of 6 cycles of chemotherapy. The main metabolites of ferrokinetics were studied: GP25, ferritin, soluble transferrin receptors, transferrin, iron, erythropoietin, IL-6 and CRP indices. The control group consisted of 29 apparently healthy women.Results. AS was detected in 14 (45.1 %) of breast cancer patients. IDA prevailed with microcytic, hypochromic characteristics of erythrocytes, a low concentration of ferritin, iron, GP25, IL-6, CRP, and a high level of transferrin and soluble transferrin receptors. A some patients were diagnosed with FID, mainly with the III and IV stages of the disease. Unlike IDA, they had a high concentration of ferritin, CRP and significant production of GP25, IL-6. Erythropoietin level was not optimal for the majority of patients with AS. A few patients on the background of treatment with recombinant erythropoietins revealed a deficiency of vitamins B12 (cyanocobalamin) and folic acid.Conclusion. Early diagnosis, a personalized approach to the prescription of iron preparations, recombinant erythropoietins, vitamins B12 and folic acid in patients with AS allowed for 6 cycles neoadjuvant chemotherapy without a significant decrease in erythrocytes, hemoglobin and hematocrit in most of them. The data obtained on IL-6, GP25, and CRP indicate relationship between them in the development of FID in breast cancer patients with a widespread tumor process and require further study.

Anaemia in Heart Failure Patients, Associated with Angiotensin - Renin - Aldosterone System Altering Medications.

Heart failure (HF) remains one of the most common diseases and one of the major causes of death worldwide. HF is often associated with other chronic diseases, most commonly with anemia. Anemia increases patients' mortality and lowers their quality of life. There are a few pathophysiological mechanisms that explain anemia in patients with HF – hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, chronic kidney disease, and impaired erythropoietin production and activity. Moreover, congestive HF is often treated with angiotensin-converting enzyme inhibitors and aldosterone receptors blockers, which could be linked to the development of anemia.

Holding Iron Measurement to a Gold Standard: Comparing Reticulocyte Hemoglobin Content to Traditional Biomarkers in Predicting Response to Intravenous Iron Supplementation in Hemodialysis Patients

Background: Patients suffering from end stage renal disease (ESRD) commonly develop functional and absolute iron deficiency due to various etiologies, requiring regular intravenous iron supplementation. Current methods of quantifying iron stores, such as serum iron and transferrin saturation (TSAT), may be inaccurate measures for detecting functional iron deficiency. This increases the likelihood of incomplete correction of iron deficiency or the risk of developing iron overload, both resulting in higher healthcare and administrative costs. Recent studies focusing on reticulocyte hemoglobin content (CHr) have shown it to be a specific and sensitive indicator of absolute and functional iron deficiency.Aims: To determine whether CHr is a more sensitive and accurate surrogate measure of response to iron infusion than traditional measurements such as serum iron and TSAT.Methods: We performed a retrospective chart review of patients aged ≥18 years with ESRD receiving dialysis and regular intravenous iron infusions at University of Iowa Hospitals and Clinics between October 2016 and March 2017 who also had applicable serial laboratory monitoring. Parameters analyzed included hemoglobin, hematocrit, CHr, serum iron, TSAT, total iron binding capacity, and ferritin. 3 months later, along with the total dose of iron infused over that specific timeframe, we obtained subsequent sets of these values.Results: Fifty-three eligible patients were identified, of which 63% were male and 37% female with a median age of 59 years. The median time interval between initial and subsequent laboratory testing was 91 days; the median cumulative iron infusion was 300 mg with doses ranging from 0 to 2100 mg. Correlation between variables of interest and iron dosing were calculated for serum iron (p = 0.49), TSAT (p = 0.16), and CHr (p = 0.99). With removal of subjects who had received the median 300 mg dose, correlation coefficients were recalculated for serum iron (p = 0.49), TSAT (p = 0.21), and CHr (p = 0.93).Conclusions: Contrary to published data, our study did not show any statistically significant support for CHr as a superior predictor of response to iron infusion when compared to traditional biomarkers. Our negative finding could be tempered by small sample size; this data was also not adjusted for other factors including hemoglobin level or erythropoiesis-stimulating agent administration. Given their reported resilience in response to acute fluctuations in patient inflammatory states and potentially decreased cost of testing versus the traditional iron panel, interest in reticulocyte parameters remains high. We plan to control for or identify any confounding factors by performing a prospective cohort study on a larger population to further elucidate the validity of this finding. DisclosuresNo relevant conflicts of interest to declare.

Clinical characteristic, red blood cell indices, iron profile and prognosis of heart failure in females

Background: Heart failure is a leading killer worldwide, with concurrent anaemia and iron deficiency portending sepulchral prognosis. Anaemia is rampant, with 53% prevalence in Indian females, but iron deficiency can be present even without anaemia. Therefore, this study was planned to determine the clinical profile, red blood cell indices, and effects of iron deficiency, on the course and prognosis of heart failure in Indian females.Materials and methods: This was a hospital-based observational study, conducted at a tertiary care teaching institute in India. Data from 147 females enrolled in the study between September 2017 to March 2020 was collected out of all patients enrolled in ongoing heart failure registry at the institute. Clinical characteristics at presentation, iron profile, red blood cell indices, treatment and mortality data was collected.Results: Mean age of the subjects (n = 147) was 53.31 ± 17.1 years with 55% non-rheumatic and 45% with rheumatic heart disease. The patients with rheumatic heart disease were younger, with a higher prevalence of atrial fibrillation. Non-rheumatic patients had a higher prevalence of CV risk factors like diabetes, hypertension, renal failure, more patients in NYHA IV, and 83% patients had LVEF ≤40%. Anaemia was present in 49%, however iron deficiency was present in 89% (absolute iron deficiency in 80% and functional iron deficiency in 9%) with no significant difference between rheumatic and non-rheumatic group. Red blood cell indices showed no significant difference across the spectrum of iron deficiency and anaemia, except lower mean corpuscular volume in patients with both iron deficiency and anaemia. The mean survival time was 840 days, with no significant difference between groups. There was significantly higher mortality in patients with iron deficiency (log rank 0.045).Conclusion: Iron deficiency–with or without anaemia–is very high in Indian females, worsening survival in heart failure. Proper diagnosis with iron supplementation will improve the prognosis.

Experimental Drugs for Chemotherapy- and Cancer-Related Anemia

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients.

P498 Diagnosing and differentiating iron deficiency in inflammatory disorders: still an unsolved mystery?

Abstract Background It is well established that inflammation can mimic some aspects of iron deficiency (ID) by impairing the utilisation of existing iron stores for red cell production and inducing an iron-sequestration syndrome and hypoferraemia. Diagnosis of ID is therefore complex and there is currently no standard clinical test capable of clearly distinguishing ID when inflammation is present. Often, a combination of parameters is necessary. The aim of this study was to investigate which sole parameter or combination of parameters can best predict ID in patients with IBD. Methods A cross-sectional study was conducted using routine blood samples from patients with IBD. Blood samples were analysed for standard blood count, iron status (serum ferritin; SF, transferrin saturation; TSAT), inflammation parameters (high sensitivity C-reactive protein; hsCRP) and soluble transferrin receptor (sTfR) using standard methodology. A multiparameter index test (MCV, TSAT, SF) was performed to define patients with iron restricted erythropoiesis (IRE) (IRE group) when at least 2 of the 3 parameters indicated IRE. Cut-off values for TSAT (&amp;lt;20%) and SF (&amp;lt;30/μL) were defined according to ECCO guidelines and for MCV (80 fL) according to the literature. Criteria taken to indicate absolute ID (AID) were hsCRP &amp;lt;5 mg/L, SF 30 μg/L and TSAT &amp;lt; 20%, while functional ID (FID) was denoted by hsCRP ≥ 5 mg/L, SF &amp;lt; 100 μg/L and TSAT &amp;lt; 20%. Results 168 IBD patients (88f; 85CD/83UC;43.4±14.9y) were enrolled. Of these, 107/168 had inflammation. 100/168 patients had IRE, of whom 70/100 had FID and 30/100 had AID. ROC analysis was performed to compare different parameters as detectors of IRE and to summarise the performance of each respective parameter (Table 1). When inflammation was absent, the best combination was SF and TSAT, whereas in the presence of inflammation, the best combination was found to be TSAT and sTfR. The addition of MCV, which showed high specificity regardless of inflammation, was found to add additional value to the diagnosis in the context of inflammation (p &amp;lt;0.001). Conclusion Of those parameters studied, none was suitable to diagnose IRE when taken alone. In the absence of inflammation, ID in IBD can be adequately determined by combining SF and TSAT. When inflammation is present, however, the combination of TSAT with sTfR measurement was found to be more accurate, while the additional inclusion of MCV added additional value to the diagnosis.

Impact of iron deficiency on prognosis of heart failure patients with preserved ejection fraction

Objective: To investigate the impact of iron deficiency (ID) on prognosis in heart failure patients with preserved ejection fraction (HFpEF). Methods: A total of 215 consecutive patients with HFpEF, who visited the cardiovascular outpatient department of Beijing Anzhen Hospital, were enrolled in this prospective study. The plasma ferritin level and transferin saturation were measured. Patients were divided into two groups: ID group and non-ID group. ID patients were further divided into absolute ID subgroup and functional ID subgroup. Patients were followed up to 1 year. The endpoints of the study were all-cause mortality and rehospitalization for heart failure (HF). The independent predictors of outcome were determined by Cox regression model. The quality of life of patients was evaluated at the end of the follow-up. Results: The age of this patient cohort was (67±8) years, 39.1% patients were male. The prevalence of ID was 54.4%. Within one year of follow-up, 37 patients (17.2%) died and 70 patients (32.6%) were rehospitalized for HF. Compared to non-ID group, patients in ID group were older, had higher heart rate, lower plasma hemoglobin level and estimated glomerular filtration rate (eGFR) value, had a higher prevalence of anemia and chronic kidney disease (P all<0.05). Kaplan-Meier curves showed that all-cause mortality and rehospitalization for HF in HFpEF patients with ID were higher than patients without ID, and prognosis was similar between patients with absolute ID and functional ID. Multivariable regression analysis showed that ID was an independent predictor for all-cause mortality and rehospitalization for HF in HFpEF patients. The of 6 minutes walking distance was shorter ((356.0±98.3)m vs. (389.2±94.3)m, P=0.023), and the value in Kansas city cardiomyopathy questionnaire was lower ((58.06±10.43) m vs. (61.51±11.64) m, P = 0.039) in patients with ID than patients without ID. Conclusion: In patients with chronic HFpEF, ID is an independent predictor for all-cause mortality and rehospitalization for HF at one year of follow-up, independent of the types of ID.

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies.1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

Preoperative patient blood management during the SARS-CoV-2 pandemic.

Preoperative patient blood management during the SARS-CoV-2 pandemic.

Comparative Characteristics Of Ferrokinetic Parameters And Their Relationship With Inflammation In Patients With CHF In Advanced And Senile Age

To perform a comparative analysis of anemia of chronic disease (ACD) and iron-deficiency anemia (IDA) in late middle-aged and elderly patients with chronic heart failure (CHF) by ferrokinetic parameters, inflammation indexes, and their associations. Materials and methods. 65 patients with ischemic heart disease were evaluated, including 35 patients with CHF and ACD, 10 patients with CHF and IDA, and 20 patients without CHF, ACD, and IDA (control group, CG). Results. Patients with CHF and IDA had true iron deficiency whereas 54% of patients with CHF and ACD had functional iron deficiency, and 46% of patients had no iron deficiency. Levels of acute phase proteins, ferritin and hepcidin, C-reactive protein (CRP), and interleukin-6 (IL-6) were highly significantly different in patients with CHF and ACD and patients with CHF and IDA; positive and significant correlations were found for levels of IL-6 and ferritin, IL-6 and CRP, and CRP and hepcidin. In patients with CHF and IDA, levels of acute phase proteins, ferritin and hepcidin, CRP, and IL-6 were low and correlations of IL-6 with ferritin, IL-6 with CRP, and CRP with hepcidin were non-significant. Concentrations of erythropoietin were significantly higher in patients with CHF and ACD and patients with CHF and IDA compared to the control group; however, significant differences between them were absent.

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.

Intravenous iron supplementation after liver surgery: Impact on anemia, iron, and hepcidin levels—a randomized controlled trial

BackgroundAnemia is a recognized risk factor for perioperative related morbidity and mortality and is frequently reported in liver surgeries with an estimated incidence of 32%. We aim to assess the impact of intravenous iron administration in the immediate postoperative period on anemia and iron status as well as to determine the kinetics of hepcidin after liver surgery. MethodsThe HepciFer trial, a randomized controlled trial, included 50 patients undergoing liver surgery. In accordance with the randomization process, patients received either ferric carboxymaltose (15 mg/kg, maximum 1 g) or placebo 4 hours after surgery. ResultsThe mean hemoglobin level, 7 days after surgery, did not differ significantly between the intervention and control group (11.1 ± 1.8 g/dL and 10.4 ± 1.6 g/dL, respectively) with a mean difference of +0.7 g/dL ([95% confidence interval, −0.3 to +1.7], P = .173). Within patients receiving intravenous iron supplementation, none presented biological signs of functional iron deficiency. Hepcidin levels remained significantly higher during the observation period in the intervention group. Inflammatory biomarkers, red blood cells transfusion rate and hospital duration of stay were similar between groups. ConclusionIntravenous ferric carboxymaltose administration did not result in a significant increase of hemoglobin levels 7 days after surgery. However, this study suggests that intravenous iron supplementation in the immediate postoperative settings prevents functional iron deficiency. Intravenous iron supplementation overcame the hepcidin-mediated blockade of iron absorption and should be considered as the preferred route of administration in the postoperative period.

Study of serum hepcidin level and its relation to recombinant human erythropoietin resistence, markers of iron status and C-reactive protein in patients with end stage renal disease on maintenance hemodialysis.

Background: Anemia represents a significant problem to deal with in patients with chronic kidney disease (CKD) on hemodialysis (HD). This work aimed to determine the usefulness of measuring serum hepcidin level in patients with end stage renal disease (ESRD) on maintenance hemodialysis and anemia, and assess the possible correlation between serum hepcidin level and markers of iron status (serum iron, serum ferritin, total iron binding capacity and iron saturation), erythropiotin resistence and inflammatory markers (C-reactive protein). Methods: The study was performed on (50 patients) with end stage renal disease on maintainance hemodialysis. Patients were divided into two groups: group (I): 40 patients who have anemia responsive to erythropoietin therapy and group (II): 10 patients who have anemia resistant to erythropoietin therapy. All patients were subjected to thorough history taking, clinical examination, and laboratory investigations. Results: serum hepcidin level was higher in all patients with erythropoietin resistence index (ERI) 15. There was a highly significant positive correlation between serum hepcidin level and ERI and significant negative correlation between serum hepcidin level and serum iron, ferritin and transferrin saturation. But no significant correlation between serum hepcidin level and C-reactive protein. Conclusion: Hepcidin is associated with anemia, markers of iron status and erythropoietin resistence. If used as a diagnostic tool, it might improve iron therapy in patients with functional iron deficiency due to reticuloendothelial blockage of iron transport. This is important to avoid iron overload and to improve erythropoietin (EPO) response in patients with ESRD.

POS-261 ROLE OF RETICULOCYTE HAEMOGLOBIN EQUIVALENT(RET HE) IN ASSESSING IRON DEFICIENCY ANAEMIA (IDA) AND FUNCTIONAL IRON DEFICIENCY(FID) IN PATIENTS OF CHRONIC KIDNEY DISEASE

Anemia is most commonly associated feature in patients of CKD. Knowledge about the status of the iron stores, circulating iron and erythropoietin levels are important to diagnose the cause and treat anemia in patients of CKD. Ferritin is an acute phase reactant and can be falsely raised in patients of CKD. Similarly, transferrin may be falsely decreased, TIBC and TSAT may be falsely normal because of chronic disease. Hence, they cannot be relied upon. To find out the exact status of iron stores in the body and the cause of anemia in CKD, patients have to undergo investigations including iron studies, serum EPO, hepcidin levels and bone marrow perl’s staining which is quite expensive and is not routinely available IDA is diagnosed by low iron and normal EPO. FID is characterized by normal iron and EPO. Whereas EPO deficiency is characterized by normal iron and decreased EPO. This study was carried out to correlate the levels of novel marker Ret HE, serum iron profile with iron reserves. In addition, we looked at the efficacy of Ret HE in determining the cause of anemia and its utility in differentiating IDA/FID from anaemia due to EPO deficiency in patients of CKD. Ret HE is widely available, cheap and cost-effective investigation. Prospective, observational study, total of 66 patients were included. All adults diagnosed as CKD and having anaemia were included in the study. Patients were excluded if they denied consent, were diagnosed with hemoglobinopathies, hematological malignancies, hemolytic anemias, or if they had received IV iron therapy within last 6 months. Demographic data, history, physical examination, the type of management was noted and the data compiled. Bone marrow iron stores was taken as the gold standard to diagnose iron deficiency. Bone marrow iron stores was compared to the biochemical iron profile and Ret HE and the comparison between the three was made. Total of 76 (39M and 37F) patients with CKD and anaemia were included. In 10 patients bone marrow was not available hence were excluded in analysis. Out of 66 patients 15 patients had IDA, 19 had EPO deficiency and 35 had FID. Three patients had both IDA and EPO deficiency. Sensitivity and specificity of the parameters is summarized below. Ret HE was most sensitive (85.7%) for diagnosing IDA at a cut off of 27.2pg. Serum ferritin was most specific (87%) for diagnosing IDA at a cut off value of 100mcg/dl. The sensitivity and specificity of RetHE for diagnosing anaemia due to decreased available iron (IDA/FID) was highest i.e. 80% and 50% respectively at a cut off value of 27.2pg. The study results suggest low sensitivity and specificity of serum iron and TSAT in diagnosing IDA and FID and low sensitivity of serum ferritin in diagnosis IDA2. RetHE is the most sensitive marker for diagnosing both iron deficiency and functional iron deficiency is patients of CKD. 3. As RetHe cannot differentiate between IDA and FID so it should be used along with serum ferritin to diagnose the cause of anaemia in CKD patients. 4. We suggest the following to diagnose the cause of anaemia in CKD Ret HE FerritinIDA <27.2 pg <100mcg/dlFID <27.2pg >100mcg/dlEPO deficiency >27.2pg >100mcg/dl 5. Ret HE is cheap and cost-effective investigation in low income countries to diagnose iron deficiency

POS-283 HEMOGLOBIN (HB) CORRECTION WITH ROXADUSTAT IS ASSOCIATED WITH IMPROVED IRON HOMEOSTASIS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT (NDD) AND DIALYSIS-DEPENDENT (DD) CHRONIC KIDNEY DISEASE (CKD)

Anemia in CKD is caused largely by reduced erythropoietin production, decreased bone marrow responsiveness to erythropoietin, and hepcidin-induced functional iron deficiency. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases Hb by stimulating erythropoietin synthesis, increasing bone marrow responsiveness to erythropoietin, and improving iron availability. Roxadustat also decreases hepcidin and increases the expression of genes involved in iron mobility. In this post hoc analysis, we assessed the effect of treatment with roxadustat on iron parameters in patients with NDD-CKD and DD-CKD. Patients were randomized to double-blind roxadustat or placebo in three pivotal Phase 3 NDD-CKD trials (OLYMPUS, ALPS, and ANDES) and randomized to open label roxadustat or epoetin alfa in three pivotal Phase 3 DD-CKD trials (ROCKIES, SIERRAS, and HIMALAYAS). In patients with NDD-CKD, oral iron was administered without restriction per discretion of the treating physician; intravenous (IV) iron use was limited to rescue therapy. In patients with DD-CKD, IV iron was administered per usual care in the epoetin alfa group and was restricted in the roxadustat group; oral iron was not restricted in either group. Mean changes from baseline (BL) in Hb, IV iron dose, hepcidin, and iron parameters were evaluated. Pooled results per patient population are reported. Overall, 4277 patients with NDD-CKD (roxadustat N=2391; placebo N=1886; mean BL Hb 9.1 g/dL for both groups) and 3890 patients with DD-CKD (roxadustat N=1943; epoetin alfa N=1947; mean BL Hb 9.6 g/dL for roxadustat and 9.7 g/dL for epoetin alfa), including 1530 incident dialysis patients, were evaluated. In patients with NDD-CKD, mean change in Hb from BL to Weeks 28–52 was greater with roxadustat than placebo (1.9 vs 0.2 g/dL; P<0.0001). Fewer roxadustat-treated patients required IV iron than placebo-treated patients up to Week 52 (2.6% vs 6.0%; P<0.0001). Treatment with roxadustat reduced ferritin and resulted in modest reductions in transferrin saturation (TSAT) vs placebo. Roxadustat treatment increased serum iron and total iron-binding capacity (TIBC), and reduced hepcidin compared with placebo (Figure 1). In patients with DD-CKD, mean Hb increased more from BL to Weeks 28–52 with roxadustat vs epoetin alfa (1.21 vs 0.95 g/dL; P<0.0001). Roxadustat-treated patients used less monthly IV iron compared with epoetin-alfa treated patients over Weeks 28–52 (52.2 vs 66.8 mg; P<0.0001). Roxadustat reduced ferritin compared with epoetin alfa. While no changes were seen in TSAT, roxadustat increased serum iron and TIBC, and reduced hepcidin compared with epoetin alfa (Figure 2). View Large Image Figure ViewerDownload Hi-res image Download (PPT) In both patients with NDD-CKD and DD-CKD, roxadustat facilitated iron transport and utilization resulting in increases in both serum iron and TIBC, likely driven by reduced hepcidin. Overall, despite the observed greater Hb increase from BL with roxadustat, IV iron use was reduced with roxadustat in both the NDD-CKD and DD-CKD populations.

The role of interleukin-6 and hepcidin 25 in the pathogenesis of anemic syndrome associated with malignant neoplasms with breast cancer patients before neoadjuvant chemotherapy.

A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.

Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKD.

CKD is an independent risk factor for heart failure. Iron dysmetabolism potentially contributes to heart failure, but this relationship has not been well characterized in CKD. We performed a historical cohort study using data from the Veterans Affairs Corporate Data Warehouse to evaluate the relationship between iron status and heart failure hospitalization. We identified a CKD cohort with at least one set of iron indices between 2006 and 2015. The first available date of serum iron indices was identified as the study index date. The cohort was divided into four iron groups on the basis of the joint quartiles of serum transferrin saturation (shown in percent) and ferritin (shown in nanograms per milliliter): reference (16%-28%, 55-205 ng/ml), low iron (0.4%-16%, 0.9-55 ng/ml), high iron (28%-99.5%, 205-4941 ng/ml), and function iron deficiency (0.8%-16%, 109-2783 ng/ml). We compared 1-year heart failure hospitalization risk between the iron groups using matching weights derived from multinomial propensity score models and Poisson rate-based regression. A total of 78,551 veterans met the eligibility criteria. The covariates were well balanced among the iron groups after applying the propensity score weights (n=31,819). One-year adjusted relative rate for heart failure hospitalization in the iron deficiency groups were higher compared with the reference group (low iron: 1.29 [95% confidence interval, 1.19 to 1.41]; functional iron deficiency: 1.25 [95% confidence interval, 1.13 to 1.37]). The high-iron group was associated with lower 1-year relative rate of heart failure hospitalization (0.82; 95% confidence interval, 0.72 to 0.92). Furthermore, the association between iron deficiency and heart failure hospitalization risk remained consistent regardless of the diabetes status or heart failure history at baseline. Iron deficiency, regardless of cause, was associated with higher heart failure hospitalization risk in CKD. Higher iron status was associated with lower heart failure hospitalization risks.

Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents.

Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and an increased morbidity and mortality. The mechanisms involved in anemia associated to CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Patients are most commonly managed with oral or intravenous iron supplements and with erythropoiesis stimulating agents (ESA). However, these treatments have associated risks, and sometimes are insufficiently effective. Nonetheless, in the last years, there have been some remarkable advances in the treatment of CKD-related anemia, which have raised great expectations. On the one hand, a novel family of drugs has been developed: the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). These agents induce, among other effects, an increase in the production of endogenous EPO, improve iron availability and reduce hepcidin levels. Some of them have already received marketing authorization. On the other hand, recent clinical trials have elucidated important aspects of iron supplementation, which may change the treatment targets in the future. This article reviews the current knowledge of the pathophysiology CKD-related anemia, current and future therapies, the trends in patient management and the unmet goals.

Investigation and management of iron deficiency anaemia in a specialist palliative care setting and the role of intravenous iron: a descriptive analysis of hospice data.

Anaemia is common in hospice populations and associated with significant symptom burden. Guidelines recommend investigating for and treating iron deficiency (ID), but there is little evidence of this practice in palliative care populations. This report describes the results of investigations for and subsequent management of ID in a UK hospice. This is a descriptive study of routine clinical data. Laboratory and clinical records were reviewed retrospectively for 12 months following the implementation, in August 2018, of routine investigation for ID amongst patients with clinically relevant anaemia in whom treatment would be considered. Absolute (AID) and functional iron deficiency (FID) were diagnosed using established definitions and treatments recorded. Iron status was evaluated in 112 cases, representing 25/110 (22.7%) of those with mild, 46/76 (60.5%) moderate and 41/54 (75.9%) severe anaemia. Twenty-eight (25%) were defined as having AID, 48 (42.8%) FID and 36 (32%) no ID. There was a significant difference between groups in symptoms triggering haemoglobin check and diagnosis, with a higher proportion of patients with classic symptoms of anaemia and gastrointestinal malignancy in those with AID. Intravenous iron was given on 12 occasions in the hospice with no major adverse events. Subjective symptom benefit in 7 cases and a statistically significant increase in overall mean haemoglobin were observed. This report describes the outcome of investigations for iron deficiency in patients with clinically significant anaemia in a UK hospice. Results indicate iron deficiency is common and can be safely treated with intravenous iron replacement, within current guidelines, in a hospice setting. Further research should define the optimum use of this approach in palliative care patients.