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Hypophosphatemia resulting from intravenous iron treatment has become an increasingly concerning syndrome in recent years. We report the case of a 66-year-old male patient with a medical history of ankylosing spondylitis (AS), Crohn's disease, and chronic iron deficiency. Following intravenous iron infusions of ferric carboxymaltose, the patient developed diffuse bone pain and multiple bone fractures. After ruling out that the pain was in the context of spondyloarthritis (SpA), the diagnosis of osteomalacia associated with hypophosphatemia was established based on his clinical history, complementary analytical, and imaging tests. Once the diagnosis was made, intravenous ferric carboxymaltose infusions were discontinued, and oral calcium and vitamin D supplementation were initiated, resulting in clinical improvement with serum phosphate levels' normalization. This case shows the importance of recognizing the risk factors and clinical findings in selected patients, monitoring phosphate levels in those with high risk factors and considering stopping or switching to another intravenous iron formulation. Furthermore, this case highlights the importance of maintaining clinical suspicion of other possible etiologies of pain in patients with SpA. [ABSTRACT FROM AUTHOR]

After a young female patient received an intravenous iron infusion for severe symptomatic iron-deficiency-anemia, a severe hypophosphatemia was diagnosed with associated mild muscle weakness. With renal phosphate loss and elevated serum FGF23 (Fibroblast Growth Factor 23), the diagnosis of a hypophosphatemia caused by ferric carboxymaltose (Ferinject®) was made. Upregulation of FGF23 inhibits renal phosphate reabsorption and also the activation of vitamin D, which additionally reduces intestinal phosphate absorption. The symptoms of hypophosphatemia may be masked after iron replacement. [ABSTRACT FROM AUTHOR]

Background and Aims: To evaluate the safety and patient experience of a hospital‐initiated home‐based iron infusion service in patients with iron deficiency with or without anaemia. Methods: Retrospective cohort study, including adult patients who received intravenous iron through a Hospital in The Home service in a single tertiary centre between August 2020 and 2021. A chart review was conducted for documented adverse events (AEs). A telephone survey assessed patient acceptance with three questions on a 5‐point Likert scale: (i) How do you perceive the experience of having your infusion given in the home? (ii) Would you like to have the infusion in the same location if you require one in the future? and (iii) Do you feel safe having your infusion at home? Outcome measures: Percentage of patients experiencing AEs and patient acceptance of a home‐based iron infusion strategy. Results: One hundred ninety‐seven patients were included (181 ferric carboxymaltose and 16 ferric derisomaltose). Six (3%) patients (2 of 181 patients who received ferric carboxymaltose compared with 4 of 16 patients who received ferric derisomaltose, P < 0.001, Fisher's exact) experienced AEs, mostly headache and pruritus. Most patients who participated in the telephone survey had a positive experience (57/58 (98%)), felt safe (57/58 (98%)) and preferred future infusions to occur at home (52/58 (90%)). Conclusion: A home‐based iron infusion strategy was safe and well accepted by patients. Larger studies evaluating the safety profile of different iron formulations in the home setting are required. [ABSTRACT FROM AUTHOR]

Background: Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) severity. Methods: This retrospective cohort study included parenteral iron recipients who did not receive erythropoiesis-stimulating agents (ESA) between 2017 and 2019. The study cohort was derived from two groups of patients: those managed by the CKD team and patients being optimised for surgery in the pre-operative clinic. Patients were categorized based on their kidney function: Patients with normal kidney function [estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2] were compared to those with CKD stages 3–5 (eGFR < 60 mL/min/1.73 m2). Patients were further stratified by the type of iron deficiency [absolute iron deficiency (AID) versus functional iron deficiency (FID)]. The key outcome was change in hemoglobin (∆Hb) between pre- and post-infusion haemoglobin (Hb) values. Parenteral iron response was assessed using propensity-score matching and multivariate linear regression. The impact of kidney impairment versus the nature of iron deficiency (AID vs. FID) in response was explored. Results: 732 subjects (mean age 66 ± 17 years, 56% females and 87% White) were evaluated. No significant differences were observed in the time to repeat Hb among CKD stages and FID/AID patients. The Hb rise was significantly lower with lower kidney function (non-CKD and CKD1–2; 13 g/L, CKD3–5; 7 g/L; p < 0.001). When groups with different degrees of renal impairment were propensity-score matched according to whether iron deficiency was due to AID or FID, the level of CKD was found not to be relevant to Hb responses [unmatched (∆Hb) 12.1 vs. 8.7 g/L; matched (∆Hb) 12.4 vs. 12.1 g/L in non-CKD and CKD1–2 versus CKD3–5, respectively]. However, a comparison of patients with AID and FID, while controlling for the degree of CKD, indicated that patients with FID exhibited a diminished Hb response regardless of their level of kidney impairment. Conclusion: The nature of iron deficiency rather than the severity of CKD has a stronger impact on Hb response to intravenous iron with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment. [ABSTRACT FROM AUTHOR]

Abstract Aims There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)‐related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta‐analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV‐related outcomes in patients with HF. Method and results PubMed/Medline was searched using the following terms: (‘intravenous’ and ‘iron’ and ‘heart failure’) from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all‐cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF [RR 0.0.85; 95% CI (0.77, 0.95)], first hospitalization for HF [RR 0.82; 95% CI (0.67, 0.99)], and total hospitalizations for HF [RR 0.74; 95% CI (0.60, 0.91)] but no statistically significant difference in all‐cause mortality [RR 0.95; 95% CI. (0.83, 1.09)] or CV mortality [OR 0.89; 95% CI (0.75, 1.05)]. Conclusions Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all‐cause mortality or CV mortality alone.

Introduction: Iron deficiency is a common condition, especially among patients with kidney and heart failure and inflammatory bowel disease. Intravenous iron is the preferred method of treatment in these patients, but it usually requires prolonged iron polymaltose infusions or multiple administrations of alternative preparations. The aim of the study was to confirm the safety and patient acceptance of ultrarapid iron polymaltose infusions as an alternative to slower treatments and ferric carboxymaltose. Method: An open-label, phase 4 safety study was conducted at a tertiary hospital, with consenting participants diagnosed with iron deficiency and requiring iron polymaltose up to 1,500 mg receiving the infusion over 15 min. The acute adverse event (AE) rates and their severities were compared to historical controls of 1- and 4-h iron polymaltose infusions from a retrospective study of 648 patients from the same study site. Delayed AEs as well as participant infusion acceptability were also studied. Results: Three hundred participants over a 2-year period received ultrarapid infusions of iron polymaltose with an acute AE rate of 18.7% and severe AE rate of 1.0%. The total and mild infusion AE rates were higher compared to those of slower infusions (p < 0.001), but comparable for moderate and severe AEs. Delayed reactions occurred in 12.5% of participants, with over 95% of them preferring repeat ultrarapid infusions if required again. Conclusion: Iron polymaltose can be safely infused at ultrarapid rates when compared to slower infusions, with similar safety to ferric carboxymaltose, offering greater convenience for patients and reduced healthcare costs.

Aims: There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)‐related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta‐analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV‐related outcomes in patients with HF. Method and results: PubMed/Medline was searched using the following terms: ('intravenous' and 'iron' and 'heart failure') from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all‐cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF [RR 0.0.85; 95% CI (0.77, 0.95)], first hospitalization for HF [RR 0.82; 95% CI (0.67, 0.99)], and total hospitalizations for HF [RR 0.74; 95% CI (0.60, 0.91)] but no statistically significant difference in all‐cause mortality [RR 0.95; 95% CI. (0.83, 1.09)] or CV mortality [OR 0.89; 95% CI (0.75, 1.05)]. Conclusions: Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all‐cause mortality or CV mortality alone. [ABSTRACT FROM AUTHOR]

Background: Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) severity. Methods: This retrospective cohort study included parenteral iron recipients who did not receive erythropoiesis-stimulating agents (ESA) between 2017 and 2019. The study cohort was derived from two groups of patients: those managed by the CKD team and patients being optimised for surgery in the pre-operative clinic. Patients were categorized based on their kidney function: Patients with normal kidney function [estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2] were compared to those with CKD stages 3–5 (eGFR < 60 mL/min/1.73 m2). Patients were further stratified by the type of iron deficiency [absolute iron deficiency (AID) versus functional iron deficiency (FID)]. The key outcome was change in hemoglobin (∆Hb) between pre- and post-infusion haemoglobin (Hb) values. Parenteral iron response was assessed using propensity-score matching and multivariate linear regression. The impact of kidney impairment versus the nature of iron deficiency (AID vs. FID) in response was explored. Results: 732 subjects (mean age 66 ± 17 years, 56% females and 87% White) were evaluated. No significant differences were observed in the time to repeat Hb among CKD stages and FID/AID patients. The Hb rise was significantly lower with lower kidney function (non-CKD and CKD1–2; 13 g/L, CKD3–5; 7 g/L; p < 0.001). When groups with different degrees of renal impairment were propensity-score matched according to whether iron deficiency was due to AID or FID, the level of CKD was found not to be relevant to Hb responses [unmatched (∆Hb) 12.1 vs. 8.7 g/L; matched (∆Hb) 12.4 vs. 12.1 g/L in non-CKD and CKD1–2 versus CKD3–5, respectively]. However, a comparison of patients with AID and FID, while controlling for the degree of CKD, indicated that patients with FID exhibited a diminished Hb response regardless of their level of kidney impairment. Conclusion: The nature of iron deficiency rather than the severity of CKD has a stronger impact on Hb response to intravenous iron with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment.

Randomized control trials (RCTs) have shown that certain intravenous iron preparations can induce high levels of fibroblast growth factor 23 (FGF‐23) and persistent hypophosphatemia. Repeated iron infusions may lead to prolonged hypophosphatemia and osteomalacia events not captured by RCTs. Several previous case reports have described skeletal adverse effects after repeated iron infusions. To characterize these effects, we conducted a systematic review of case reports. MEDLINE, Embase, Web of Science, and Cochrane databases were searched in March 2021. We selected case reports of patients ≥16 years old. Study quality was assessed using the tool from Murad and colleagues. We report the results in a narrative summary. We identified 28 case reports, reporting 30 cases. Ages ranged from 28 to 80 years (median 50 years). Most patients (n = 18) received ferric carboxymaltose (FCM), whereas 8 received saccharated ferric oxide (SFO) and 3 received iron polymaltose (IPM). All but 2 cases had more than five infusions (range 2 to 198, median 17). The lowest phosphate levels ranged from 0.16 to 0.77 mmol/L (median 0.36 mmol/L). Intact FGF‐23 (iFGF‐23) was high when measured. Serum 25OH vitamin D was low in 10 of 21 cases measured and 1,25(OH)2 vitamin D in 12 of 18. Alkaline phosphatase was high in 18 of 22 cases. Bone or muscle pain was reported in 28 of the 30 cases. Twenty patients had pseudofractures, 9 had fractures, and 6 patients had both. All 15 available bone scans showed focal isotope uptake. Case reports tend to report severe cases, so potential reporting bias should be considered. Osteomalacia is a potential complication of repeated iron infusion, especially in patients with gastrointestinal disorders receiving prolonged therapy. Pain and fractures or pseudofractures are common clinical findings, associated with low phosphate, high iFGF‐23, high alkaline phosphatase, and abnormal isotope bone scan. Discontinuing or switching the iron formulation was an effective intervention in most cases. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Iron deficiency and depression are prevalent comorbidities in the setting of heart failure. Both conditions are associated with poorer patient outcomes including mortality, hospitalisation and quality of life. Iron replacement has come to the fore as a means to improve patient outcomes. This review aims to assess the current literature regarding the benefits of iron supplementation for iron deficient heart failure patients including potential improvements in depression. The databases of Medline, EMBASE, the Cochrane library of systematic reviews, Central Register of Controlled Trials, PubMed, Web of Science and ClinicalTrials.gov were searched for studies with relevant patient outcomes. A total of 18 studies were identified and included in the review. In essence, intravenous iron was found to be beneficial for New York Heart Association (NYHA) classification, quality of life measures, heart failure (HF) hospitalisation and aerobic capacity. Oral iron however was not beneficial. Research surrounding intravenous iron improving cardiovascular mortality, time to first hospitalisation and changes in depression status is lacking. Further research is required to elucidate the advantages of intravenous iron for iron deficient heart failure patients on their depression, mortality and first admission to hospital. Consensus is required regarding which form of iron and the treatment regime that should be adopted for future clinical guidelines. [ABSTRACT FROM AUTHOR]

Key Clinical Message Hypophosphatemia postintravenous iron is frequent but under‐recognized. If prolonged or recurrent, it can cause osteomalacia. The likely mechanisms are direct toxicity to proximal tubular cells causing phosphate wasting, elevated Fibroblast growth factor‐23 (FGF‐23), and reduced 1,25‐dihydroxyvitamin D (1,25(OH)2D). Hypophosphatemia may be severe and persist for months, necessitating phosphate replacement until normalization of serum levels occurs.

Objective: Studies have demonstrated that antepartum intravenous iron sucrose infusion (IVFe) is safe and improves predelivery hemoglobin (Hb). Yet, there is little data guiding timing of administration or number of doses required to be impactful. We sought to determine if timing of antepartum IVFe and number of doses provided impacts efficacy.Methods: We performed a retrospective cohort study of women who obtained prenatal care and delivered at our institution 10/1/2015-10/30/2017. Women with a third-trimester hemoglobin (Hb) < 9.5 g/dL were included. Women with hemoglobinopathies and those who received an antepartum blood transfusion were excluded. Women receiving ≥1 antepartum 300 mg IVFe dose were considered in the IVFe group.Results: Five-hundred-twenty-three (6.1%) of 8563 delivering women were included. Sixty-five (12.4%) of included women received IVFe. By timing of IVFe, the earlier IVFe was received before delivery, the greater the median Hb increase (No IVFe: Δ0.8g/dL, IVFe 0-1 weeks predelivery: Δ0.05 g/dL, 1-2 weeks: Δ0.9 g/dL, 2-4 weeks: Δ1.5 g/dL, 4-6 weeks: Δ1.8 g/dL, 6-8 weeks: Δ1.8 g/dL, 8-12 weeks: Δ2.75 g/dL, p = .0001). When comparing each stratum to the No IVFe group, only those receiving IVFe >2 weeks before delivery had a significant increase in Hb level from third trimester to delivery. By the number of IVFe doses, increasing administrations incrementally impacted Hb difference from third trimester to delivery, with only those receiving at least 3 doses demonstrating statistically significant Hb change compared to the No IVFe group.Conclusion: Antepartum IVFe effectively increases Hb from the third trimester to delivery admission when administered 2-12 weeks predelivery. There is increasing benefit the further out the IVFe is administered and with an increasing number of doses. Initiatives to combat antepartum anemia should focus on early detection and treatment to best optimize outcomes. [ABSTRACT FROM AUTHOR]

It has been demonstrated that iron deposition in the kidney is a harbinger of poor prognosis, but it is not clear whether kidney failure/damage predisposes iron deposition, or iron deposition activates an oxidative cascade and causes kidney damage. Until this issue is clarified, it will be difficult to predict the risks or benefits of any iron infusion for chronic kidney disease. [ABSTRACT FROM AUTHOR]

We present a 45-year-old woman with complex gastrointestinal anatomy leading to short gut syndrome and chronic diarrhea who was admitted with symptomatic severe hypophosphatemia attributed to renal phosphate wasting induced by intravenous iron preparation ferric carboxymaltose. She was maintained on intravenous phosphate replacements. The treatment course was complicated by respiratory illness leading to volume depletion, acute kidney injury, and phosphate nephropathy. She developed chronic kidney disease and underwent kidney transplant. Our case report aims to increase awareness of hypophosphatemia related to ferric carboxymaltose. [ABSTRACT FROM AUTHOR]

One hundred and ninety‐four patient episodes were audited for response to a standardised 1 g intravenous iron infusion for medical outpatients with iron deficiency anaemia. Patients received either ferric carboxymaltose or iron polymaltose. At 5–7 weeks after infusion, mean increase in Hb was 26.7 g/L and ferritin was 161 mcg/L, and only one patient had Hb <100 g/L. This reassures that 1 g dose of intravenous iron is sufficient for most patients, with benefits for treatment costs and patient convenience. [ABSTRACT FROM AUTHOR]

The mechanism of action of fibroblast growth factor‐23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long‐term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Hypophosphatemia postintravenous iron is frequent but under‐recognized. If prolonged or recurrent, it can cause osteomalacia. The likely mechanisms are direct toxicity to proximal tubular cells causing phosphate wasting, elevated Fibroblast growth factor‐23 (FGF‐23), and reduced 1,25‐dihydroxyvitamin D (1,25(OH)2D). Hypophosphatemia may be severe and persist for months, necessitating phosphate replacement until normalization of serum levels occurs. [ABSTRACT FROM AUTHOR]

Denosumab-induced hypocalcemia and iron infusion-related hypophosphatemia are both well described. We describe a case of severe hypocalcemia and hypophosphatemia following sequential denosumab and parenteral iron administration. This resulted in respiratory failure due to muscle weakness and cardiac arrhythmia, requiring noninvasive ventilation and urgent intravenous electrolyte replacement. This case highlights the severe dysregulation in calcium and phosphate homeostasis that can occur with denosumab and iron infusions when administered in quick succession. Given that these drugs are among the most common therapies prescribed across a range of specialties, we hope to alert clinicians to this potential serious drug-drug interaction and suggest strategies for monitoring and management of the electrolyte derangement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Intravenous (IV) iron therapy is performed in community practices and hospitals with modern formulations when oral administration becomes impractical. Effective replacement of iron is important for the treatment of iron deficiency and anemia. Can IV iron be rechallenged in individuals with a history of adverse reactions? This review is to explore the challenge of this, when clinically indicated., Methods: After performing a literature search, five studies (combined total sample number=1,006) for re-exposure of IV iron to individuals with a history of past reactions were identified, observed, and analyzed. Re-exposure included reactions ranging from mild to moderate and few cases of severe type., Results: The majority (>80%) of IV iron rechallenges were tolerable, safe, and successful without major serious incidents. There were no reports of major reactions (severe hypersensitivity reactions or anaphylaxis) in these re-exposures., Conclusion: Re-administration of IV iron therapy in patients with a previous adverse reaction is plausible, with benefit and risk stratification. A rechallenge would depend on the nature and degree of the adverse reaction and use of alternative formulations. Rechallenge to a previous severe hypersensitivity reaction or anaphylaxis with the same product has not been reported in these studies. Evidence on the benefit of premedication use is conflicting and requires further studies.

ABSTRACT: Intravenous infusions of different iron formulations are recognized as a cause of hypophosphatemia. Chronic hypophosphatemia can alter bone metabolism and bone material structure. As a consequence, osteomalacia may develop and lead to bone fragility. Herein, we report a patient with Crohn's disease presenting with persistent hypophosphatemia and insufficiency fractures while receiving regular iron infusions due to chronic gastrointestinal bleeding. Previously, the patient regularly received vitamin D and also zoledronic acid. The patient underwent bone biopsy of the iliac crest that showed typical signs of osteomalacia with dramatically increased osteoid volume and decreased bone formation. Analysis of the bone mineralization density distribution (BMDD) revealed a more complex picture: On the one hand, there was a shift to higher matrix mineralization, presumably owing to low bone turnover; on the other hand, a broadening of the BMDD indicating more heterogeneous mineralization due to osteomalacia was also evident. This is the first report on changes of bone histomorphometry and bone matrix mineralization in iron‐induced osteomalacia. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: Intravenous iron affects serum levels of intact fibroblast growth factor-23 (iFGF23) and its cleavage product c-terminal FGF23 (cFGF23) in iron-deficient people with normal renal function. We hypothesized that intravenous iron modulates iFGF23 and cFGF23 in haemodialysis patients differently according to the type of iron used. Methods: Prevalent, stable haemodialysis patients requiring protocol-based intravenous iron therapy were randomized to a single 200 mg dose of either ferric carboxymaltose (FCM) or iron sucrose (IS). The primary outcome was change in iFGF23 and cFGF23 from pre-infusion to Day 2 post-infusion. Serum hepcidin, ferritin and phosphate were also measured. Pair-wise comparisons utilised the Wilcoxon rank sum test; linear mixed models with an interaction term for treatment and time evaluated between-group effects. Results: Forty-two participants completed the study. In those randomized to FCM (n = 22), median (interquartile range) values pre-infusion and Day 2, respectively, were 843 pg/mL (313-1922) and 576 pg/mL (356-1296, p = 0.05) for iFGF23, 704RU/mL (475-1204) and 813RU/mL (267-1156, p = 0.04) for cFGF23, and 1.53 mmol/L (1.14-1.71) and 1. 37 (1.05-1.67, p = 0.03) for phosphate. These parameters did not change following IS. Both serum ferritin (p < 0.001) and hepcidin (p < 0.001) increased in both groups, and the increase in hepcidin was greater in the FCM group (p = 0.03 for between-group difference). Conclusions: Contrary to iron-deficient people with normal renal function, haemodialysis patients given protocoldriven intravenous FCM demonstrated a fall in iFGF23 and a rise in cFGF23, changes not evident with IS. This suggests a differential effect of intravenous iron treatment according to both formulation and renal function. Trial registration: Australian and New Zealand Clinical Trials Register ACTRN12614000548639. Registered 22 May 2014 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Intravenous correction of iron deficiency by total dose iron polymaltose is inexpensive and safe, but current protocols entail prolonged administration over more than 4 h. This results in reduced patient acceptance, and hospital resource strain. We aimed to assess prospectively the safety of a rapid intravenous protocol and compare this with historical controls. Methods: Consecutive patients in whom intravenous iron replacement was indicated were invited to have up to 1.5 g iron polymaltose by a 58-min infusion protocol after an initial 15-min test dose without pre-medication. Infusion-related adverse events (AE) and delayed AE over the ensuing 5 days were also prospectively documented and graded as mild, moderate or severe. Results: One hundred patients, 63 female, mean age 54 (range 18-85) years were studied. Thirty-four infusion-related AE to iron polymaltose occurred in a total of 24 patients - 25 mild, 8 moderate and 1 severe; higher than previously reported for a slow protocol iron infusion. Thirty-one delayed AE occurred in 26 patients - 26 mild, 3 moderate and 2 severe; similar to previously reported. All but five patients reported they would prefer iron replacement through the rapid protocol again. The presence of inflammatory bowel disease (IBD) predicted infusion-related reactions (54% vs 14% without IBD, P < 0.001) and the serum C-reactive protein was higher in those with reactions (P = 0.043). Conclusion: Iron polymaltose can be successfully administered using a rapid total dose infusion protocol and was well accepted by patients. It offers significant cost, resource utilization and time benefits for the patient and hospital system. [ABSTRACT FROM AUTHOR]

Background: Intravenous iron is commonly administered to anaemic patients to treat iron deficiency, but due to its ferric colouration, it may interfere with the spectrophotometric assessment of haemoglobin concentrations. This paper investigates the potential interference of three clinically used intravenous iron preparations on the measurement of haemoglobin.Methods: Haemoglobin concentration was measured for neat and Hartmann's solution-diluted iron polymaltose, carboxymaltose and sucrose solutions using bedside (Radiometer HemoCue®), point-of-care (Radiometer ABL800 Flex) and laboratory (Abbott CellDyne Sapphire™) devices. Haemoglobin concentration was then assessed with the same devices utilizing anaemic whole blood with the iron solutions added.Results: Neat iron preparations registered clinically significant haemoglobin concentrations on bedside and laboratory measurements. When intravenous iron preparations were diluted to clinical concentrations, their effect on haemoglobin measurements, either in isolation or mixed with anaemic blood, was negligible.Conclusion: Although neat preparations of intravenous iron do interfere with spectrophotometric analysis of haemoglobin, concentrations likely to be seen post iron infusion do not significantly interfere with haemoglobin measurement. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS. Methods: The study was a randomized, parallel-group double-blind study of 1000mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra. Results: At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit. Conclusions: High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies. [Copyright &y& Elsevier]

Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde-deoxyguanosine-adducts (M 1 dG) with an immunoslot blot technique. HD-patients ( n =21) showed a significant increase of total DNA damage ( p <10 -12 ), compared to controls ( n =12). In a subset of patients and controls, GSSG levels and M 1 dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate ( p <0.001). In patients receiving iron infusion during HD, MDA-formation ( n =11) and total DNA damage ( n =10) were additionally increased ( p <0.005). Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion. [ABSTRACT FROM AUTHOR]

Iron is known to induce lipid perocidation and recent evidence indicates that both iron and lipid peroxidation are elevated in the substantia nigra in Parkinson's disease (PD). To test whether excess intranigral iron induces lipid peroxidation, we infused an iron citrate solution (0.63 nmol in 0.25 μL) into the rat substantia nigra and measured nigral thiobarbituric acid reactive products at 1-h, 1-d, 1-wk, and 1-mo postinfusion. In a separate group of iron-infused animals, histologic analysis within the substantia nigra through 1-mo postinfusion was accomplished by thionine- and iron-staining, with concurrent assessment of striatal neurochemical markers. Concentrations of nigral thiobarbituric acid reactive products were significantly elevated at 1 h and 1 d in iron-infused animals compared to vehicle-infused and unoperated animals, with a return to control values by 1 wk. Similarly, striatal dopamine turnover was acutely elevated, suggesting damage to dopaminergic neurons, which was confirmed histologically. Although iron-staining within the iron diffusionary area was increased through the postinfusion month, there was an apparent progression of the cellular character of staining from predominantly neuronal to reactive glial and finally to oligodendroglial by 1 mo postinfusion. this progression of cellular iron-staining may indicate a shifting of infused iron to a more bound unreactive form, thus explaining only an acute elevation in lipid peroxidation through 1 d following intranigral iron infusion. The data indicate that damage to nigral neurons induced by iron infusion is transciently associated with a marker of oxidative damage and supports the possibility that iron-induced oxidative stress contributes to the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

We present a 45-year-old woman with complex gastrointestinal anatomy leading to short gut syndrome and chronic diarrhea who was admitted with symptomatic severe hypophosphatemia attributed to renal phosphate wasting induced by intravenous iron preparation ferric carboxymaltose. She was maintained on intravenous phosphate replacements. The treatment course was complicated by respiratory illness leading to volume depletion, acute kidney injury, and phosphate nephropathy. She developed chronic kidney disease and underwent kidney transplant. Our case report aims to increase awareness of hypophosphatemia related to ferric carboxymaltose., (Copyright © 2021 Baylor University Medical Center.)

Iron-induced hypophosphataemic osteomalacia remains under-recognized as a potential complication of parenteral iron therapy. We here report two cases of symptomatic hypophosphataemic osteomalacia with multiple insufficiency fractures in the context of chronic gastrointestinal blood loss, necessitating monthly iron polymaltose infusions over prolonged periods of time. Respective blood tests revealed severe hypophosphataemia [0.29 and 0.43; normal range (NR) 0.8-1.5 mmol/l] in the presence of normal serum calcium and 25-hydroxy vitamin D levels. Urinary fractional phosphate excretion was elevated (16% and 24%; NR < 5%) and the tubular maximum phosphate reabsorption was reduced, consistent with renal phosphate wasting. Serum fibroblast growth factor 23 (FGF23) obtained in one patient was significantly elevated at 285 pg/ml (NR < 54 pg/ml). Bone mineral density was significantly reduced and whole-body bone scans revealed metabolic bone disease and multiple insufficiency fractures consistent with osteomalacia. Cessation of iron infusions resulted in clinical and biochemical improvement within 2 months in one patient whereas the second patient required phosphate and calcitriol supplementation to improve symptomatically. Iron-induced hypophosphataemic osteomalacia is thought to be due to reduced degradation of FGF23, resulting in phosphaturia and reduced synthesis of 1,25-dihydroxy vitamin D. Monitoring of patients on long-term parenteral iron is recommended to avoid clinically serious adverse effects., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.