Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

BACKGROUND AND AIMS: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. METHODS: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. RESULTS: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. CONCLUSIONS: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

Current iron therapy in the light of regulation, intestinal microbiome, and toxicity: are we prescribing too much iron?

Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron deficiency, while in industrialized nations, reduced food intake and dietary preferences affect iron status. Other causes that can lead to iron deficiency are conditions and diseases that result in reduced intestinal iron absorption and blood loss. In addition, iron absorption and its bioavailability are influenced by the composition of the diet. Individuals with increased iron needs, including infants, adolescents, and athletes, are particularly vulnerable to deficiency. Severe iron deficiency can lead to anemia with performance intolerance or shortness of breath. In addition, even without anemia, iron deficiency leads to mental and physical fatigue, which points to the fundamental biological importance of iron, especially in mitochondrial function and the respiratory chain. Standard oral iron supplementation often results in gastrointestinal side effects and poor compliance. Low-dose iron therapy seems to be a valid and reasonable therapeutic option due to reduced hepatic hepcidin formation, facilitating efficient iron resorption, replenishment of iron storage, and causing significantly fewer side effects. Elevated iron levels influence gut microbiota composition, favoring pathogenic bacteria and potentially disrupting metabolic and immune functions. Protective bacteria, such as bifidobacteria and lactobacilli, are particularly susceptible to increased iron levels. Dysbiosis resulting from iron supplementation may contribute to gastrointestinal disorders, inflammatory bowel disease, and metabolic disturbances. Furthermore, gut microbiota alterations have been linked to mental health issues. Future iron therapy should consider low-dose supplementation to mitigate adverse effects and the impact on the gut microbiome. A comprehensive understanding of the interplay between iron intake, gut microbiota, and human health is crucial for optimizing therapeutic approaches and minimizing potential risks associated with iron supplementation.

Identification and management of preoperative anaemia in adults: A British Society for Haematology Guideline update.

This updated British Society for Haematology guideline provides an up-to-date literature review and recommendations regarding the identification and management of preoperative anaemia. This includes guidance on thresholds for the diagnosis of anaemia and the diagnosis and management of iron deficiency in the preoperative context. Guidance on the appropriate use of erythropoiesis-stimulating agents and preoperative transfusion is also provided.

Anemia diagnosis and therapy in malignant diseases: implementation of guidelines-a representative study.

PURPOSE: Anemia in cancer should be diagnosed and treated according to guideline recommendations. The implementation of ESMO and German guidelines and their effect on anemia correction was analyzed. METHODS: This retrospective epidemiological study, representative for Germany, analyzed data on anemia management of cancer patients with anemia ≥ grade 2. The Guideline Adherence Score (GLAD) for diagnosis (GLAD-D) and therapy (GLAD-T) was defined as follows: 2 points for complete, 1 point for partial, 0 point for no adherence. RESULTS: Data were analyzed for 1046 patients. Hb levels at diagnosis of anemia were 8-10 g/dL in 899 (85.9%) patients, 7-8 g/dL in 92 (8.7%), and < 7 g/dL (5.0%) in 52. Transferrin saturation was determined in 19% of patients. Four hundred fifty-six patients received RBC (43.6%), 198 (18.9%) iron replacement, 106 (10.1%) ESA, and 60 (5.7%) vitamin B12 replacement. 60.6% of patients receiving iron replacement were treated intravenously and 39.4% were treated orally. Two hundred eighty-eight (36.6%) of 785 patients receiving transfusions had no guideline-directed indication. GLAD-D was 2 in 310 patients (29.6%), 1 in 168 (16.1%), and 0 in 568 (54.3%). GLAD-T was 2 in 270 patients (25.8%), 1 in 320 patients (30.6%), and 0 in 456 patients (43.6%). Higher GLAD-D significantly correlated with higher GLAD-T (τB = 0.176, p < 0.001). GLAD-T 2 was significantly associated with greater Hb increase than GLAD-T 0/1 (p < 0.001) at 28 days (10.2 vs. 9.7 g/dL) and at 2 months (10.4 vs. 9.9 g/dL). CONCLUSIONS: Anemia assessment is inadequate, transfusion rates too high, and iron and ESA therapy too infrequent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05190263, date: 2022-01-13.

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.

BACKGROUND: Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs). METHODS: A comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I2 statistics and Egger's test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis. RESULTS: The findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I2) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I2 = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I2 = 97.88%, p = 0.000). CONCLUSION: Iron therapy in any form may reduce anemia's burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future. TRIAL REGISTRATION: Registered with PROSPERO and ID is CRD42020185033.

Association between serum phosphate levels and anemia in non-dialysis patients with chronic kidney disease: a retrospective cross-sectional study from the Fuji City CKD Network.

BACKGROUND: Patients with chronic kidney disease (CKD) present high mortality and morbidity rates despite the availability of various therapies. Although CKD-mineral and bone disorder (MBD) and renal anemia are important factors in patients with CKD, only few studies have analyzed the relationship between them. Therefore, this study aimed to evaluate the relationship between CKD-MBD and anemia in patients with CKD who did not receive erythropoiesis-stimulating agent or iron therapies. METHODS: This retrospective cross-sectional study included patients with CKD aged ≥ 20 years with estimated glomerular filtration rate (eGFR) categories G2a to G5 who were referred to the Fuji City General Hospital between April 2018 and July 2019. The exclusion criterion was ongoing treatment for CKD-MBD and/or anemia. RESULTS: The data of 300 patients with CKD were analyzed in this study. The median age of patients was 71 (range, 56.5-79) years. The median eGFR was 34 (range, 20-48) mL/min/1.73 m2, and the mean hemoglobin (Hb) level was 12.7 g/dL (standard deviation, 2.3), which decreased as the CKD stage increased. In a multivariate linear regression analysis of anemia-related factors, including age, renal function (eGFR), nutritional status, inflammation, and iron dynamics (serum iron level, total iron-binding capacity, ferritin levels), the serum phosphate levels were significantly associated with the Hb levels (coefficient [95% confidence interval], -0.73 [-1.1, -0.35]; P < 0.001). Subgroup analysis revealed a robust association between serum phosphate levels and Hb levels in the low-ferritin (coefficient [95% confidence interval], -0.94 [-1.53, -0.35]; P = 0.002) and advanced CKD groups (coefficient [95% confidence interval], -0.89 [-1.37, -0.41]; P < 0.001). CONCLUSIONS: We found an association between high serum phosphate levels and low Hb levels in patients with CKD not receiving treatment for anemia. These results underscore the possibility of a mechanistic overlap between CKD-MBD and anemia.

[Management of iron deficiency in chronic heart failure].

Iron deficiency is frequent in patients with chronic heart failure (CHF) with a prevalence of 50%, and its frequency varies depending on the study groups. The presence of iron deficiency limits erythropoiesis, leading to the development of anemia over time in patients with CHF, regardless of gender, race, and left ventricular ejection fraction (LVEF). Observational studies demonstrate a higher prevalence of iron deficiency in women and in patients with higher NYHA (New York Heart Association) functional class, decreased LVEF, increased brain natriuretic peptide (NT-proBNP), or increased high-sensitivity C-reactive protein. Iron deficiency and anemia in patients with CHF are independently associated with a decreased exercise capacity, hospitalizations for CHF, an increase in overall mortality and mortality from cardiovascular diseases. The clinical significance of iron deficiency requires the need to diagnose iron metabolism in all patients with CHF. Current guidelines for the diagnosis and treatment of CHF indicate the need to determine the level of ferritin and saturation of transferrin in all patients with a suspected diagnosis of heart failure. The use of oral iron therapy in patients with CHF demonstrates its low efficacy in correcting this condition according to the clinical trials. At the same time the use of intravenous iron therapy is safe and improves symptoms, exercise capacity and quality of life in patients with heart failure with reduced ejection fraction and iron deficiency, which has been shown both in international placebo-controlled trials and meta-analyses. The use of iron carboxymaltose should improve CHF symptoms, exercise capacity and quality of life in patients with CHF and LVEF45%. Intravenous iron therapy has also been shown to reduce readmissions for CHF in patients with an LVEF50% who have recently been hospitalized for worsening CHF.

Iron Deficiency and the Small bowel​.

PURPOSE OF REVIEW: This article reviews iron deficiency anemia (IDA) and suspected small bowel bleeding (SSBB) from initial consultation through laboratory evaluation, endoscopic evaluation, and therapeutic options. RECENT FINDINGS: Recent guidelines on management of SSBB, IDA, video capsule endoscopy (VCE), and device-assisted enteroscopy (DAE) are reviewed. The advantages and limitations of VCE, DAE, and imaging are discussed. Medical treatment for refractory small bowel bleeding is discussed. Evaluation of IDA starts with a detailed history and physical exam. Additional lab work can establish the diagnosis of IDA and evaluate for associated conditions. If initial endoscopic tests are unrevealing, SSBB should be ruled out. Further investigation can be performed using video capsule endoscopy (VCE), device-assisted enteroscopy (DAE), and imaging. The mainstay of medical treatment of IDA secondary to SSBB is iron supplementation. Additional treatment is tailored to the pathology and may include medical, endoscopic and surgical options.

Does iron therapy have a place in the management of all breath-holding spells?

BACKGROUND: Aim of this study was to analyze the effect of iron therapy in children with breath-holding spells, irrespective of their hemoglobin level. METHOD: All of the children were evaluated in terms of age, sex, age at onset of the attack, attack frequency, type of breath-holding spell, family pedigree, laboratory values. All enrolled patients were given iron at the dose of 4 mg/kg/day as a single daily dose for 3 months. Patients were called for follow-up appointments 1 and 3 months after the initiation of treatment to record the frequency and severity of spells. RESULTS: The mean age of the patients was 12.50 ± 9.51 months. Patients were divided into two groups according to the hemoglobin level. The frequency of anemia in children with spells was recorded as 27%. Out of 100 patients treated with iron, 43% showed complete remission at the end of 1 month. At the end of the 3 months, percentage of complete responders increased to 80%. After three-month of iron treatment, 96.2% of the anemic and 73.97% of the non-anemic patients were spell-free. Eight children had mild adverse effects after iron therapy that did not require dose modification. CONCLUSIONS: This study confirmed that iron therapy reduces spell frequency regardless of anemia in all breath-holding spells. A three-month empiric iron therapy should be offered to all children with spells.

Preoperative Anemia in Primary Arthroplasty Patients-Prevalence, Influence on Outcome, and the Effect of Treatment.

BACKGROUND: This study aims to: 1) Determine the prevalence of preoperative anemia in arthroplasty; 2) Assess whether preoperative anemia is associated with inferior outcomes; and 3) Ascertain whether optimization in a dedicated blood management program (BMP) is associated with improved outcomes. METHODS: All primary arthroplasties performed at an academic, tertiary-care, arthroplasty center between 2012 and 2017 were reviewed. Hemoglobin level obtained in the preoperative assessment clinic was recorded. Patients with anemia were then considered for further review in BMP. Outcomes included improvement in hemoglobin level post-BMP; length of stay; perioperative transfusion; 90-day readmission, complication, and reoperation rates. The effect of preoperative anemia and the effect of treatment at the BMP on outcomes were evaluated through multivariable regression analysis controlling for relevant covariates. RESULTS: 17% of patients (932/5384) were found to have anemia; 115/357 patients who attended the BMP were no longer anemic. Thus, at time of operation, 15% of patients (817/5384) had anemia. Anemic patients were 4.09 times more likely (95% CI: 2.64-6.35) to require a transfusion; 1.42 times more likely (95% CI: 0.99-2.03) to sustain complications and had 19% longer (95% CI: 13%-26%) length of stay. Those who attended the BMP were less likely to receive a transfusion (OR = 0.32, 95% CI: 0.16-0.66), suffer from postoperative complications (OR = 0.30, 95% CI: 0.14-0.63), or require readmission compared with anemic patients not seen in the BMP (OR = 0.25, 95% CI: 0.09-0.71). CONCLUSIONS: The prevalence of anemia in this arthroplasty cohort was 15%. Preoperative, timely, optimization of anemia should be strongly considered as it is likely to reduce "anemia-associated burden" after arthroplasty.

Iron Therapy in Chronic Kidney Disease: Days of Future Past.

Anemia affects millions of patients with chronic kidney disease (CKD) and prompt iron supplementation can lead to reductions in the required dose of erythropoiesis-stimulating agents, thereby reducing medical costs. Oral and intravenous (IV) traditional iron preparations are considered far from ideal, primarily due to gastrointestinal intolerability and the potential risk of infusion reactions, respectively. Fortunately, the emergence of novel iron replacement therapies has engendered a paradigm shift in the treatment of iron deficiency anemia in patients with CKD. For example, oral ferric citrate is an efficacious and safe phosphate binder that increases iron stores to maintain hemoglobin levels. Additional benefits include reductions in fibroblast growth factor 23 levels and the activation of 1,25 dihydroxyvitamin D. The new-generation IV iron preparations ferumoxytol, iron isomaltoside 1000, and ferric carboxymaltose are characterized by a reduced risk of infusion reactions and are clinically well tolerated as a rapid high-dose infusion. In patients undergoing hemodialysis (HD), ferric pyrophosphate citrate (FPC) administered through dialysate enables the replacement of ongoing uremic and HD-related iron loss. FPC transports iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Moreover, this paper summarizes recent advancements of hypoxia-inducible factor prolyl hydroxylase inhibitors and future perspectives in renal anemia management.

Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group.

Iron deficiency is the most prevalent nutritional deficiency affecting children and adolescents worldwide. A consistent body of epidemiological data demonstrates an increased incidence of iron deficiency at three timepoints: in the neonatal period, in preschool children, and in adolescents, where it particularly affects females.Conclusion: This narrative review focuses on the most suggestive symptoms of iron deficiency in childhood, describes the diagnostic procedures in situations with or without anemia, and provides Swiss expert-based management recommendations for the pediatric context.What is Known:• Iron deficiency (ID) is one of the most common challenges faced by pediatricians.• Significant progress in the diagnosis and therapy of ID has been made over the last decade.What is New:• Our expert panel provides ID management recommendations based on the best available evidence.• They include strategies for ID diagnosis and therapy, both oral and intravenous.

The Effectiveness of Daily and Alternate Day Oral Iron Supplementation in Athletes With Suboptimal Iron Status (Part 2).

The authors compared the effectiveness of daily (DAY) versus alternate day (ALT) oral iron supplementation in athletes with suboptimal iron. Endurance-trained runners (nine males and 22 females), with serum ferritin (sFer) concentrations <50 µg/L, supplemented with oral iron either DAY or ALT for 8 weeks. Serum ferritin was measured at baseline and at fortnightly intervals. Hemoglobin mass (Hbmass) was measured pre- and postintervention in a participant subset (n = 10). Linear mixed-effects models were used to assess the effectiveness of the two strategies on sFer and Hbmass. There were no sFer treatment (p = .928) or interaction (p = .877) effects; however, sFer did increase (19.7 µg/L; p < .001) over the 8-week intervention in both groups. In addition, sFer was 21.2 µg/L higher (p < .001) in males than females. No Hbmass treatment (p = .146) or interaction (p = .249) effects existed; however, a significant effect for sex indicated that Hbmass was 140.85 g higher (p = .004) in males compared with females. Training load (p = .001) and dietary iron intake (p = .015) also affected Hbmass. Finally, there were six complaints of severe gastrointestinal side effects in DAY, but only one in ALT. In summary, both supplement strategies increased sFer in athletes with suboptimal iron status; however, the ALT approach was associated with lower incidence of gastrointestinal upset.

The Effectiveness of Transdermal Iron Patches in Athletes With Suboptimal Iron Status (Part 1).

The authors compared the effectiveness of two modes of daily iron supplementation in athletes with suboptimal iron stores: oral iron (PILL) versus transdermal iron (PATCH). Endurance-trained runners (nine males and 20 females), with serum ferritin concentrations <50 µg/L, supplemented with oral iron or iron patches for 8 weeks, in a parallel group study design. Serum ferritin was measured at baseline and fortnightly intervals. Hemoglobin mass and maximal oxygen consumption (V˙O2max) were measured preintervention and postintervention in PATCH. A linear mixed effects model was used to assess the effectiveness of each mode of supplementation on sFer. A repeated-measures analysis of variance was used to assess hemoglobin mass and V˙O2max outcomes in PATCH. There was a significant time effect (p < .001), sex effect (p = .013), and Time × Group interaction (p = .009) for sFer. At Week 6, PILL had significantly greater sFer compared with PATCH (15.27 µg/L greater in PILL; p = .019). Serum ferritin was 15.53 µg/L greater overall in males compared with females (p = .013). There were no significant differences in hemoglobin mass (p = .727) or V˙O2max (p = .929) preintervention to postintervention in PATCH. Finally, there were six complaints of severe gastrointestinal side effects in PILL and none in PATCH. Therefore, this study concluded that PILL effectively increased sFer in athletes with suboptimal iron stores, whereas PATCH showed no beneficial effects.

Improving Anemia in Inflammatory Bowel Disease: Impact of the Anemia Care Pathway.

BACKGROUND: Anemia is a common complication of inflammatory bowel disease (IBD). Despite existing guidelines for anemia in IBD, it is frequently under-treated and the prevalence of anemia has remained high. To address this gap, the Crohn's and Colitis Foundation developed the Anemia Care Pathway (ACP). AIMS: To implement the ACP in a managed care setting and identify where it improves practice habits and where barriers remain. METHODS: The ACP was implemented from July 2016 through June 2017 and retrospectively studied. Run charts were used to identify shifts in iron deficiency screening and treatment as well as anemia prevalence. Results were compared to those of other providers in the same center not using the ACP. RESULTS: 640 IBD encounters were studied. In the ACP clinic (n = 213), anemics received iron therapy in only 30% of encounters at baseline but improved to 80%. Concurrently, anemia prevalence decreased from 48 to 25%. Screening for iron deficiency, however, did not improve. No shifts were seen in the non-ACP clinics (n = 427) across the same period despite awareness of the ACP and other guidelines. CONCLUSIONS: Across 1 year, we observed gaps in the screening and treatment of anemia in IBD. Although screening rates did not improve, the ACP appeared to reduce missed opportunities for iron therapy by about half. Most importantly, this was associated with an overall decrease in anemia prevalence. Future refinements to the ACP should be focused on enhanced screening and follow-up.

[Various scenarios for billing and remuneration of preoperative management of iron deficiency anemia in the German healthcare system]. / Verschiedene Szenarien zu Abrechnung und Kostenerstattung eines präoperativen Managements der Eisenmangelanämie im deutschen Gesundheitssystem.

More than 30% of all patients undergoing surgery suffer from preoperative anemia. Iron deficiency anemia is the most common type of anemia. The diagnostics and treatment of iron deficiency anemia can be carried out before patients undergo surgery as an alternative to blood transfusion and is an interdisciplinary task. This article gives an overview of various billing modalities and payment arrangements for management of preoperative anemia in the German healthcare system.

Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.

BACKGROUND/AIMS: Both iron deficiency and chronic inflammation are highly prevalent in patients with chronic kidney disease (CKD). The effect of intravenous iron infusion on mineral metabolism in CKD may be modified by inflammation. Intravenous iron theraphy may reduce peripheral degradation, secretion, clearence of iFGF23 and lead to hypophosphatemia. The aim of the study was to evaluate the effect of intravenous iron on mineral metabolism in CKD patients. METHODS: 35 non-dialysis patients with CKD stages 3-5. received 100 mg/24h of ferric oxide saccharated solution for 5 days. Serum calcium (Ca), phosphorus (P), parathormone (PTH), intact-FGF23 (iFGF23), C-terminal-FGF23 (cFGF23), bone alkaline phosphatase (BAP) and high-sensitive CRP were assessed on day 1 and 3 at baseline and 2 hours after each dose administration and once on day 6. Plasma iFGF23 and cFGF23, as well as serum BAP were measured with ELISA and other parameters with standard automated laboratory methods. RESULTS: Serum iFGF23 increased after iv iron on day 1 and 6 (from 268.9±446.5 to 326.3±529.9 on day 1; p=0.05 and to 451.4±601 pg/mL on day 6; p=0.03). cFGF23 was reduced only on day 1 (from 654.3±441.3 to 473.6±414 RU/mL; p=0.016). P concentration decreased significantly two hours after the first iron infusion (from 1.69±0.5 to 1.54±0.35 mmol/l; p=0.003). In following days the changes of cFGF23, P and of other calcium-phosphate metabolism were not significant. Serum CRP correlated neither with iFGF-23 nor cFGF-23. CONCLUSION: Intravenous iron supplementation may only transiently affect the production and degradation of FGF23 resulting in hypophosphatemia at the commencement of iron therapy. Chronic low-grade inflammation does not seem to play a role in that mechanism.

Impact of ferric carboxymaltose on the evolution of hemoglobin and ECOG performance status in iron-deficient patients with solid tumors: a 3-month follow-up retrospective study.

BACKGROUND: Anemia is often associated with a lower quality of life and less tolerance to treatments in cancer patients. OBJECTIVE: The aims of this retrospective study were to assess the biological (hemoglobin, Hb) and clinical (ECOG index) impact of ferric carboxymaltose (FCM) and to identify predictive factors of response in cancer patients with iron deficiency. METHODS: We included 133 patients with solid tumors who received at least one dose of FCM in 2015. RESULTS: At baseline, most patients had metastatic cancer (70%), were undergoing chemotherapy (82%), suffered from anemia (90%), and 72% had an ECOG 0-1 index. Mean Hb level was statistically higher at M1 (108.3 g/L ± 13.9), M2 (110.3 g/L ± 16.1), and M3 (111.7 g/L ± 12.6) than M0 (99.2 g/L ± 13.9). Mean ECOG score increased significantly at M1 (1.31 ± 0.80) and M2 (1.31 ± 0.87) compared to M0 (1.13 ± 0.80). Variations of ECOG index between M0 and M1 were independent of levels of Hb and ferritin at inclusion and pretreatment use of transfusion and ESAs. Increase of Hb level was higher in patients with Hb < 100 g/L, ferritinemia < 800 ng/ml, or transfused before inclusion. In multivariate analysis, an ECOG index of 0 was the only predictive factor of an increase of ECOG index and Hb level < 100 g/L and ferritinemia < 800 ng/ml were predictive of an increase in Hb. CONCLUSION: Even though there was no improvement in ECOG index, this study did identify an increase of Hb for patients receiving FCM, indicating its potential benefit in iron-deficient cancer patients.