Iron Dextran Group Research Articles

Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig

Iron is emerging as a key player in aging-associated diseases due to its propensity for driving free radical formation. Studies examining the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. Our objective was to establish a direct relationship between excess iron and OA by administering iron dextran to a guinea pig strain with decreased propensity for developing this disease. Twenty, 12-week-old Strain 13 guinea pigs received either iron dextran or dextran control intraperitoneally once weekly for 4 weeks; termination occurred at 16 weeks of age. Iron levels were determined systemically (serum and liver) and within diarthrodial joints [femoral head articular cartilage and infrapatellar fat pads (IFPs) of knee joints]. One knee was collected to score structural changes associated with OA via microcomputed tomography (microCT) and histology using published grading schemes. Articular cartilage and IFPs were harvested from contralateral knees for gene expression analyses. Iron overload was confirmed systemically via increased serum iron and liver iron concentration. Articular cartilage and IFPs in the iron dextran group also had higher levels of iron. Excess iron worsened knee OA using both microCT and histologic scoring systems. Gene analyses revealed that exogenous iron altered the expression of iron trafficking proteins, select cytokines, and structural components of cartilage. These results demonstrate that systemic iron overload caused cellular iron accumulation in the knee joint. This excess iron is associated with increased expression of local inflammatory mediators and early onset and progression of knee joint OA in Strain 13 animals.

Comparison of intravenous low molecular weight iron dextran and intravenous iron sucrose for the correction of anaemia in pre-dialysis chronic kidney disease patients: a randomized single-centre study in Nigeria.

BackgroundIntravenous low molecular weight iron dextran and iron sucrose have been used for correction of iron deficiency for many years and have been shown to improve anaemia in chronic kidney disease (CKD). However, there is a paucity of head to head comparisons of these parenteral iron preparations. Such comparative efficacy data would be of particular interest in resource-limited African countries, where the majority of CKD patients are unable to afford erythropoiesis-stimulating agents. Therefore, the aim of this study was to compare the effects of these two intravenous iron preparations in pre-dialysis CKD patients.MethodsSixty-seven anaemic pre-dialysis CKD patients were randomized to one of two treatment groups. The low molecular weight iron dextran group (n = 33) received 1000 mg of low molecular weight iron dextran intravenously in four divided doses of 250 mg. The iron sucrose group (n = 34) received 1000 mg of iron sucrose intravenously in five divided doses of 200 mg. Complete blood count, serum creatinine, serum iron, unsaturated iron binding capacity, serum ferritin and transferrin saturation were assessed at baseline. The baseline parameters were repeated in all patients on Day 24. The primary outcome was the proportion of patients achieving a rise in haemoglobin (Hb) concentration of ≥1.0 g/dL after iron therapy.ResultsThere was no significant difference in the proportion of patients achieving the primary end point between both arms of the study: [7 (21.9%) low molecular weight iron dextran versus 11 (32.4%) iron sucrose; relative risk 0.68, 95% confidence interval (CI): 0.19–1.70; P = 0.23]. At Day 24, the mean increase in Hb concentration from baseline was comparable between the two groups: low molecular weight iron dextran 0.4 ± 0.7 g/dL versus iron sucrose 0.6 ± 0.9 g/dL, mean difference 0.2 g/dL (95% CI: −0.26–0.61; P = 0.28). The proportion of patients that experienced at least one or more adverse events was 27.3% in the iron dextran group versus 14.7% in the iron sucrose arm (P = 0.21).ConclusionBoth intravenous low molecular weight iron dextran and intravenous iron sucrose are effective in correcting iron deficiency and anaemia in pre-dialysis CKD patients.

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study.

BackgroundIntravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective, but with possible adverse effects. Currently, prospective studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents.MethodsWe conducted a prospective, double-blind, randomized controlled trial (RCT) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran, Infufer®, with intravenous iron sucrose, Venofer®, in non-hemodialysis adult outpatients. Primary outcome was the occurrence of immediate severe drug reactions.ResultsWe enrolled 143 patients in a one-year period. Overall, 45/143 (31.5 %) patients (20 iron dextran, 25 iron sucrose) developed 48 infusion reactions (14 immediate, 28 delayed, and 3 both). The risk of an immediate reaction was similar in both groups, 9/73 (12.3 %) iron dextran versus 8/70 (11.4 %) iron sucrose, RR = 0.93 (95 % CI; 0.38 to 2.27). The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 (31.4 %) versus the iron dextran group 9/73 (12.3 %), RR = 2.55 (95 % CI; 1.26 to 5.15; p = 0.0078).ConclusionIn this limited feasibility study, no major differences in immediate reactions were seen, but a significantly higher number of delayed reactions were seen in the iron sucrose group. Further, under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible. Future studies should consider modifying the clinical outcomes, utilize multiple centers, and consider other emerging parenteral iron formulations. (ClinicalTrials.gov NCT005936197 January 3, 2008).

Parenteral iron therapy in the treatment of iron deficiency anemia during pregnancy: a randomized controlled trial.

To compare the efficacy and safety profile of total dose infusion of low molecular weight iron dextran with divided doses of intravenous iron sucrose for the treatment of iron deficiency anemia during pregnancy. Randomized controlled trial. Shifa International Hospital, Islamabad, over a period of two years from January 2008 to December 2009. Pregnant women at gestational age more than 12 weeks with the confirmed diagnosis of Iron Deficiency Anemia (IDA) were divided into two groups. In the group-A, intravenous iron sucrose was given in divided doses while in the group-B, total daily intake of Low Molecular Weight (LMW) of iron dextran was given. Post-infusion Hemoglobin (Hb) was checked at 4 weeks and at the time of delivery for both groups. Paired sample t-test is applied and comparison (in terms of rise in hemoglobin from pre to post) of both groups was not found to be significant. In the group-A (iron sucrose group), mean pre-infusion Hb levels was 9.09 ± 0.83 gm/dl. Mean increase in Hemoglobin (Hb) was 10.75 ± 1.097 gm/dl after 4 weeks of infusion and 11.06 ± 0.866 gm/dl at delivery (p < 0.001). In group-B (iron dextran group) pre-infusion haemoglobin was 8.735 ± 0.956 gm/dl and the mean increase in hemoglobin was 10.613 ± 1.22 gm/dl at 4-week while mean increase of 10.859 ± 1.11 gm/dl at the time of delivery (p < 0.001). Both LMW iron dextran, as well as iron sucrose are equally effective in treatment of IDA during pregnancy, however, LMW iron dextran has the advantage of single visit treatment.

Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women

Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. We tested the association of iron deficiency anemia with C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 55 women with a history of heavy uterine bleeding, and assessed the longitudinal biochemical response over 35 days to equivalent doses of randomly-assigned, intravenous elemental iron in the form of ferric carboxymaltose (FCM) or iron dextran. Iron deficiency was associated with markedly elevated cFGF23 (807.8 ± 123.9 relative units [RU]/mL) but normal iFGF23 (28.5 ± 1.1 pg/mL) levels at baseline. Within 24 hours of iron administration, cFGF23 levels fell by approximately 80% in both groups. In contrast, iFGF23 transiently increased in the FCM group alone, and was followed by a transient, asymptomatic reduction in serum phosphate <2.0 mg/dL in 10 women in the FCM group compared to none in the iron dextran group. Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.

Efficacy and tolerability of intravenous iron dextran and oral iron in inflammatory bowel disease

Iron deficiency anaemia is common in inflammatory bowel disease (IBD); however, the optimum route of administration of iron replacement therapy is unclear. As inflammation may limit the absorption and efficacy of oral iron, we hypothesized that in routine clinical practice IV iron would be more effective than oral iron in patients with IBD matched for disease type, extent and activity. Thirty-three IBD patients who had received IV iron dextran (Cosmofer) in 2008-2010 were identified and matched for age, sex, diagnosis and baseline disease activity, extent and behaviour to IBD patients given oral iron. Patients given IV iron dextran were more anaemic at baseline than those receiving oral iron. Although haemoglobin (Hb) concentrations were normalized in about a third of patients, and increased significantly in both groups, the mean increase in Hb after 8 weeks was greater in the iron dextran group [2.0 g/dl (0.3) vs. 0.6 g/dl (0.1), P<0.0001]. Response to oral or IV iron was unrelated to age, sex, ethnicity, disease duration, extent or activity. Fifteen percent (five out of 33) patients discontinued oral iron because of gastrointestinal side-effects and a further two out of 35 had anaphylactoid reactions to the IV iron dextran test doses. Neither of the iron formulations worsened disease activity. In routine clinical practice, in anaemic patients with IBD of similar type, extent and activity, IV Cosmofer is more efficacious in increasing Hb concentration than oral iron. Active disease does not impair the response to either IV or oral iron in patients with IBD, and neither product itself worsens disease activity.

Effect of saccharated ferric oxide and iron dextran on the metabolism of phosphorus in rats

As a means of investigating the physiologic damage to and histologic deterioration of the kidney caused by saccharated ferric oxide (SFO) and iron dextran (ID), we administered these substances intraperitoneally to rats. The rats were divided into 3 groups. Group 1 rats ( n = 7) were given SFO, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 2 rats ( n = 5) were given ID, 28 mg/kg for 9 days and 20 mg/kg for 19 days. Group 3 rats (control, n = 9) were given normal saline solution. After 28 days, serum calcium, total protein, and albumin concentrations were significantly lower in the SFO group than in the ID group. Serum phosphorus concentrations were significantly lower in the SFO group than in the control group. Serum iron concentrations were significantly higher in the ID group than in the SFO group or the control, and the fractional excretion of sodium was significantly lower in the ID group than in the control group. The percent tubular reabsorption of phosphorus was significantly greater in the ID group than in the SFO group or the control group, and the theoretical threshold concentration of phosphorus was also significantly lower in the SFO group than in the ID or the control group. Histologic examination of the kidney after treatment revealed neither iron in the tubules nor any structural damage to the tubules. ID was not found to induce hypophosphatemia, whereas SFO did. We believe that the cause of such hypophosphatemia is impaired tubular reabsorption.

A Retrospective Case Review of Adverse Drug Reactions Using Intravenous Iron in Non-Hemodialysis Patients.

Background:Intravenous iron therapy is commonly used in hemodialysis patients but has not been well studied in other patient populations. Intravenous iron has many documented adverse drug reactions and the types and incidence of reactions differ based on the type of intravenous iron therapy used. In Canada, two forms of iron therapy are currently being used: Iron dextran marketed as Infufer or DexIron and iron sucrose marketed as Venofer are available. The general consensus in the literature is that the incidence of serious adverse reactions is relatively low approximately 0.6–0.7% with intravenous iron dextran. The objective of this retrospective chart review was to observe recorded adverse events of iron dextran (Infufer) and iron sucrose (Venofer) in our own non-hemodialysis patients.Methods:240 non-hemodialysis adult outpatient charts were reviewed. Iron dextran (Infufer) or iron sucrose (Venofer) infusions were recorded from July 20, 2000 to July 13, 2004. For each chart, the patient age, sex, date of birth, past medical history, medications and allergies were recorded. The type of intravenous iron, if premedication was used, and a description of any reaction if it occurred was also recorded. Each adverse reaction was graded on causality, severity, and system classification based on WHO standards done by two investigators virtually blinded to the type of iron therapy used.Results:Of the 240 patient charts reviewed, there were a total of 403 intravenous iron infusions given within the study period. The age of the patients ranged from 19 to 91 with mean age 60.3 +/− 16.3. The majority of our patients were end-stage renal disease peritoneal dialysis patients 187 (78%). 11 (5%) had a history of connective tissue disease or vasculitis, 15 (6%) had a history of asthma, and 84 (35%) used an angiotension converting enzyme inhibitor (ACEI). Only 17 patients (38 total infusions) received premedication.The total number of adverse events of all descriptions was 103 (26%) of the 403 total intravenous iron infusions. This was equally distributed to males 40 out of 156 (26%) and females 63 out of 247 (26%). Of the 365 intravenous therapies not given premedication there were 89 (24%) adverse events. The total number of "certain severe allergic" reactions (CSAs) was 25/403 (6%). In iron dextran (Infufer) a total of 77/295 (26%) ADRs were noted and CSAs of 23/295 (8%). In iron sucrose (Venofer) there was a total of 26/105 (25%) ADRs and 2/105 (2%) CSAs.Of the 295 intravenous iron dextran infusions, 209 had a test dose given. Of these 209, there were 60 ADRs - 25 during the test dose (12%) and 35 (17%) after the test dose.Conclusions:Adverse events and CSAs in our adult outpatient non-hemodialysis patients receiving intravenous iron therapy with either iron dextran (Infufer) and iron sucrose (Venofer) are much higher than previously reported in the literature. There are more ADRs and CSAs in the iron dextran group than the iron sucrose group. Premedication did not appear to reduce ADRs. Having a normal test dose did not preclude to getting ADRs afterwards.

Effect of iron prophylaxis on morbidity due to infectious disease: report on clinical studies in Papua New Guinea

A controlled trial of iron prophylaxis (3 ml intramuscular iron dextran) to two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The initial hypothesis was that iron deficiency increased susceptibility to infections and thus iron supplementation in a situation of actual or potential iron deficiency would diminish this susceptibility. Findings detailed elsewhere indicate that the placebo control group became relatively iron deficient and that the iron dextran group had adequate iron stores and a higher mean haemoglobin; however, prevalence of malaria recorded in the field was higher in the iron dextran group. Analysis of field and hospital infectious morbidity in the trial indicated a deleterious effect of iron dextran for all causes and for respiratory infections (the main single reason for admission). Total duration of stay in hospital was significantly increased in the iron dextran group. Analysis of other factors showed (i) a deleterious effect of low weight for height at the start of the trial; (ii) a significant positive correlation between birth haemoglobin and hospital morbidity rates and a positive interaction between haemoglobin and iron dextran on hospital morbidity. A possible association between malarial experience and other infectious morbidity is discussed.

Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was (i) a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; (ii) a lower haemoglobin associated with malaria when compared with the placebo group and (iii) a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.

Iron metabolism in the newborn infant

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was (i) a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; (ii) a lower haemoglobin associated with malaria when compared with the placebo group and (iii) a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.