ferlixit and Kidney-Failure--Chronic

A number of intravenous iron formulations have been developed over the past 65 years which rely on dextran or other compounds to prevent uncontrolled release of free iron to the circulation. High molecular weight dextran was associated with a number of serious adverse reactions and was removed from markets worldwide in 2009. The preponderance of published evidence suggests that the formulations of parenteral iron currently available in the United States, including low molecular weight iron dextran, are all safe and effective and there are no major, clinically important differences among them in terms of either efficacy or safety. For patients with chemotherapy induced anemia or with anemia of end stage renal disease who are being treated with hemodialysis, it is reasonable to use any of the iron formulations, including iron sucrose and ferric gluconate, as frequent patient encounters with health caregivers are a routine part of care and the need to administer multiple low doses of IV iron is not a major disadvantage. However, a single infusion of a total iron dose is as effective and safe when giving iron preparations containing low molecular weight iron dextran, ferumoxytol, iron isomaltoside, or ferric carboxymaltose. Use of a single total dose infusion results in a decreased number of intravenous infusions with a lower cumulative risk for infusion reactions or extravasations, a reduced need for multiple office visits and repeated utilization of medical staff, and increased convenience for physicians and patients.

Topics: Anemia; Drug Compounding; Ferric Compounds; Ferrosoferric Oxide; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Maltose; Renal Dialysis

Iron deficiency is common in patients on chronic dialysis, and most require iron-replacement therapy. In addition to absolute iron deficiency, many patients have functional iron deficiency as shown by a suboptimal response to the use of erythropoietin-stimulating agents. Both absolute and functional iron-deficiency anemia have been shown to respond to intravenous (IV) iron replacement. Although parenteral iron is an efficacious method and superior to standard doses of oral iron in patients on hemodialysis, there are ongoing safety concerns about repeated exposure potentially enhancing infection risk and cardiovascular disease. Each IV iron product is composed of an iron core with a carbohydrate shell. The avidity of iron binding and the type of carbohydrate shell play roles in the safe maximal dose and the frequency and severity of acute infusion reactions. All IV iron products are taken up into the reticuloendothelial system where the shell is metabolized and the iron is stored within tissue ferritin or exported to circulating transferrin. IV iron can be given as large intermittent doses (loading therapy) or in smaller doses at frequent intervals (maintenance dosing regimen). Limited trial data and observational data suggest that a maintenance dosing regimen is more efficacious and possibly safer than loading therapy. There is no consensus regarding the preferred method of iron repletion in patients on peritoneal dialysis, although small studies comparing oral and parenteral iron regimens in these patients have shown the latter to be more efficacious. Use of IV iron in virtually all hemodialysis and many peritoneal dialysis patients remains the standard of care.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Hemoglobins; Humans; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Renal Dialysis; Transferrin

Iron deficiency often occurs in patients with chronic kidney disease and can be effectively treated with parenteral supplementation of iron. In these patients, prompt application of iron therapy can help to reduce the dependence of erythropoietin-stimulating agents and effectively treat anemia. Correct evaluation of iron metabolism in CKD patients can be difficult. Duration of and response to therapy should always be considered while planning parenteral supplementation of iron. The main safety aspects of parenteral iron preparations relate to their possible anaphylactic potential and the potential induction of oxidative stress due to the release of free iron. However, parenteral iron supplementation is usually safe and without major side effects. Regarding current data, none of the iron preparations is showing definitive superiority. Although uncommon, iron preparations containing dextran can lead to severe side effects, therefore these preparations appear to have an inferior safety profile. Due to limited data, a comparison of third-generation iron preparations with previous preparations is not possible. Recently, for the first time, the third generation iron preparation ferumoxytol has been directly compared to iron sucrose. From this data and others, it remains unclear whether third generation iron preparations show safety-relevant superiority.

Topics: Administration, Oral; Anaphylaxis; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Humans; Infusions, Intravenous; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Oxidative Stress; Renal Dialysis

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.

Topics: Anemia; Cytokines; Endothelial Cells; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gluconates; Hematinics; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Neutrophils

Anemia associated with end stage renal disease can diminish quality of life substantially. Maintaining a stable hematocrit and stable hemoglobin levels affords many advantages. Improvement of anemia management is possible with the implementation of continuous quality improvement (CQI). Our review of the literature motivated us to switch from iron dextran injection, which can induce anaphylactic reactions and has other associated problems, to sodium ferric gluconate complex injection. This enables us to safely provide iron supplementation without the precautions that were in place for iron dextran. Our methods for creating and implementing CQI in the dialysis program at our university hospital are described.

Topics: Algorithms; Anaphylaxis; Anemia, Iron-Deficiency; Decision Trees; Erythropoietin; Ferric Compounds; Ferritins; Hemoglobins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Renal Dialysis; Total Quality Management; Transferrin

In the symposium "Anemia Management: Recognizing Opportunities and Improving Outcomes Through Nursing Interventions," Gail Wick discussed the nephrology nurse as a clinical change agent in the management of anemia of chronic renal failure. Matthew Lewis discussed the profile of sodium ferric gluconate complex, a new parenteral iron product, and Jamie Foret described his clinic's experience and research with this product. These discussions highlight how nurses, using effective and safe tools such as sodium ferric gluconate complex, can improve outcomes for hemodialysis patients.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Ferric Compounds; Ferritins; Health Services Needs and Demand; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Leadership; Nurse's Role; Nursing Assessment; Patient Care Team; Renal Dialysis; Safety; Total Quality Management; Treatment Outcome

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

Better anemia management has dramatically improved the lives of many patients with end stage renal disease (ESRD). Nephrology professionals frequently use two tools--erythropoietin and supplemental iron--to manage anemia. The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) suggests that most ESRD patients will need intravenous (i.v.) iron to optimize their response to erythropoietin. In this report, the author reviews published studies showing that i.v. iron reduces erythropoietin dose requirements, resulting in cost savings. She presents data from her center illustrating that i.v. administration of the newly approved Ferrlecit (sodium ferric gluconate) also improves anemia management and reduces erythropoietin dose requirements. The author reviews studies showing the efficacy of i.v. iron as monotherapy for anemia in ESRD patients. These data support the importance of i.v. iron as an agent to be used alone or in conjunction with erythropoietin in the management of anemia in patients with ESRD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost Savings; Drug Administration Schedule; Drug Costs; Drug Monitoring; Erythropoietin; Female; Ferric Compounds; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis; Time Factors

The use of sodium ferric gluconate in sucrose injection (Ferrlecit) in the treatment of anemia in patients with end stage renal disease (ESRD) was the major topic at the symposium "Iron Management: Innovative Solutions to Persistent Challenges," held April 14, 1999 during the annual ANNA 30th National Symposium in Baltimore, Maryland. Chairperson Susan Vogel, MHA, RN, CNN, addressed the challenges of anemia management and the limitations of oral iron supplements. She described available intravenous (i.v.) iron therapies and reviewed clinical trial data that demonstrated an excellent safety and efficacy profile for the newly approved i.v. iron supplement, sodium ferric gluconate. Suzanne Schweitzer, RPh, MPH, discussed iron metabolism and the U.S. labeling for sodium ferric gluconate, with a focus on dosing and administration. In the final presentation, Suzanne Seiler, RN, described her clinic's experience with sodium ferric gluconate and provided an experimental dosing and monitoring protocol. Together, these presentations suggest that sodium ferric gluconate is an important new tool for meeting the challenges of iron management in ESRD patients.

Topics: Anemia, Iron-Deficiency; Chemistry, Pharmaceutical; Drug Monitoring; Ferric Compounds; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis

This is a post-hoc analysis evaluating erythropoiesis stimulating agents' (ESA) related costs while using an additional ultrafilter (Estorclean PLUS) to produce ultrapure dialysis water located within the fluid pathway after the treatment with reverse osmosis and before the dialysis machine. Twenty-nine patients (19 treated with epoetin alfa and 10 with darboepoetin alfa) were included in the analysis. We showed to gain savings of 210 € per patient (35 € per patient each month) with epoetin alfa during the experimental period of 6 months, compared to the control period and of 545 € per patient (90 € per patient each month) with darboepoetin alfa. Estorclean PLUS had a cost of 600 € (25 € per month per each patient) and was used for 6 months. Intravenous iron therapy with sodium ferrigluconate had a cost of 0,545 €/62,5 mg. In conclusion, during the experimental period with the use of Estorclean, we obtained global savings of 11 € per patient per month with epoetin alfa and 30 € per patient per month with darboepoetin alfa to treat anemia in dialysis patients.

Topics: Aged; Aged, 80 and over; Anemia; Cost Savings; Costs and Cost Analysis; Cross-Over Studies; Darbepoetin alfa; Distillation; Epoetin Alfa; Female; Ferric Compounds; Filtration; Hematinics; Hemodialysis Solutions; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Water

Topics: Aged; Aged, 80 and over; Drug Administration Schedule; Female; Ferric Compounds; Ferritins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Transferrin

The relative safety of parenteral iron preparations is a controversial issue in the management of anemia in chronic kidney disease (CKD), as direct head-to-head comparative trials are lacking. In this study, patients of CKD were randomized to receive intravenous low molecular weight iron dextran (ID), sodium ferrigluconate complex (SFGC), and iron sucrose (IS) at doses and infusion rates recommended by the product manufacturer. One time test dose was used only for ID and SFGC. A total of 2,980 injections (n = 339) of i.v. iron was given, and 49 patients (14.45% per patient) and a total of 56 adverse events (1.88% per infusion) were noted. Odds ratios (OR) of serious adverse drug events (ADE; i.e., death, anaphylaxis, or suspected immuno-allergic events) per patient was not significant between ID vs. SFGC (3.566) and SFGC vs. IS (2.129), whereas that between ID vs. IS (7.594) was highly significant (p = 0.034). OR of serious ADE exposure was significantly higher in ID vs. SFGC (OR = 5.670, p = 0.0147) and ID vs. IS (OR = 7.799, p < 0.001). No significant difference was seen between the three groups in terms of non-serious ADEs. Drug discontinuation occurred significantly more often with ID. One patient who developed anaphylactoid reaction with SFGC and ID tolerated iron sucrose well.

Topics: Adult; Age Factors; Analysis of Variance; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Probability; Renal Dialysis; Risk Assessment; Severity of Illness Index; Sex Factors; Treatment Outcome

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Topics: Adult; Aged; Anemia; Drug Interactions; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose.. Prospective, open-label, crossover study.. University-affiliated general clinical research center.. Twelve ambulatory patients undergoing hemodialysis.. Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments.. Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3).. Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.

Topics: Biomarkers; Cross-Over Studies; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Prospective Studies; Renal Dialysis

Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury.. To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay.. I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters.. I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.

Topics: Acetylcysteine; Acute Kidney Injury; Aged; Aged, 80 and over; Analysis of Variance; Anemia; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Ferric Compounds; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Function Tests; Male; Malondialdehyde; Oxidative Stress; Pilot Projects; Probability; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method

Intravenous iron replacement therapy is routinely used for correction of anaemia in patients with end-stage renal failure. Free or labile iron, present both in parenteral iron formulations and in blood of haemodialysis (HD) patients, has the potential to induce severe oxidative processes. This study evaluated the acute in vivo effect of intravenous iron administration on the oxidation of plasma beta2-microglobulin (beta2m) and on its plasma levels after HD.. Iron-gluconate was administered intravenously to 14 patients receiving HD with low-flux cellulose-triacetate membranes during the first hour of the 4 h HD treatment. Each patient underwent three different dialysis treatments, during which an infusion of 62.5, 125 or 0 mg (control) of iron-gluconate was administered in random order. Plasma beta2m levels and iron parameters were monitored immediately before and after each HD treatment. The molecular isoforms of beta2m were studied by two-dimensional gel electrophoresis and western analysis. Levels of oxidized beta2m were evaluated by reaction with 2,4-dinitrophenylhydrazine and western analysis.. Both doses of iron-gluconate caused remarkable changes in the molecular properties of beta2m, including shift in isoelectric point, molecular mass and degree of oxidation. Iron administration also limited the decline in plasma beta2m levels to <7.5%, compared with 27.9+/-2.7% during HD without iron.. Intravenous iron-gluconate led to a characteristic increase in molecular weight and in negative charge of beta2m, both of which can be assumed to be consistent with reduced membrane sieving coefficients and membrane adsorption, and thus with reduced clearance of beta2m.

Topics: beta 2-Microglobulin; Diabetes Complications; Female; Ferric Compounds; Gluconates; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Renal Dialysis

Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) frequently develop anemia. Administration of recombinant human erythropoietin (rHuEPO) is effective in managing this anemia, although the additional demand for iron often results in iron deficiency. In adult patients undergoing HD, intravenous (IV) iron administration is known to replenish iron stores more effectively than oral iron administration. Nevertheless, IV iron supplementation is underutilized in pediatric patients, possibly because of unproved safety in this population. This international, multicenter study investigated the safety and efficacy of two dosing regimens (1.5 mg kg(-1) and 3.0 mg kg(-1)) of sodium ferric gluconate complex (SFGC) therapy, during eight consecutive HD sessions, in iron-deficient pediatric HD patients receiving concomitant rHuEPO therapy. Safety was evaluated in 66 patients and efficacy was evaluated in 56 patients. Significant increases from baseline were observed in both treatment groups 2 and 4 weeks after cessation of SFGC dosing for mean hemoglobin, hematocrit, transferrin saturation, serum ferritin, and reticulocyte hemoglobin content. Efficacy and safety profiles were comparable for 1.5 mg kg(-1) and 3.0 mg kg(-1) SFGC with no unexpected adverse events with either dose. Administration of SFGC was safe and efficacious in the pediatric HD population. Given the equivalent efficacy of the two doses, an initial dosing regimen of 1.5 mg kg(-1) is recommended for pediatric HD patients.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death. Although dextran, rather than iron, is believed to be the cause of these reactions, it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron, sodium ferric gluconate in sucrose (SFGC).. In a 69 center, prospective, double-blind, controlled trial of safety and tolerability of SFGC, the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations. Serum tryptase levels, a marker of mast cell degranulation, also were measured.. Among 143 iron dextran-sensitive patients exposed to SFGC, three (2.1%) were intolerant. All three had suspected allergic events to SFGC, including one patient with a serious reaction (0.7%). One dextran-sensitive patient (0.7%) had a suspected allergic reaction after placebo. In contrast, among 2194 iron dextran-tolerant patients, reactions to SFGC were significantly less common, with SFGC intolerance seen in seven patients (0.3%; P = 0.020), including five (0.2%) who had suspected allergic events (P = 0.010), but none who had serious events (0.0%; P = 0.061). Two iron dextran-tolerant patients (0.09%) had allergic-like reactions following placebo injections. Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100% increase in serum tryptase, while there were no confirmed allergic events in the iron dextran-tolerant group. Long-term exposure to SFGC in iron dextran-sensitive patients resulted in intolerance in only one additional patient and no serious adverse events.. Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients. However, logistic regression analysis, performed to account for the higher reaction rate to placebo, suggests that this increased reactivity was not drug-specific nor immunologically mediated, but represented host idiosyncrasy. These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy, and that SFGC is not a true allergen.

Topics: Drug Hypersensitivity; Female; Ferric Compounds; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Mast Cells; Middle Aged; Prospective Studies; Renal Dialysis; Serine Endopeptidases; Sucrose; Tryptases

Almost all hemodialysis (HD) patients require intravenous iron therapy to correct their anemia and maintain their iron stores. Sodium ferric gluconate complex (SFGC) is approved by the Food and Drug Administration (FDA) for treatment of iron deficiency anemia in HD patients at individual doses up to 125 mg over 10 minutes (12.5 mg/min) and has been shown to have a superior safety profile compared with iron-dextran. Higher individual doses of SFGC would permit more rapid repletion of iron stores and greater flexibility in maintenance iron therapy as well as simplify treatment of peritoneal dialysis patients and chronic kidney disease patients.. The authors reviewed the safety and tolerability of higher-dose SFGC infusions (> or =250 mg) in 144 HD patients who were previously tolerant to a single 125-mg dose of SFGC. These 144 patients received a total of 590 doses of > or =250 mg of SFGC; 571 doses were 250 mg SFGC, and most of these were infused over 1 hour, an infusion rate of 4.17 mg/min. The other 19 doses were 312.5 mg (n = 1), 375 mg (n = 14), and 500 mg (n = 4). Infusion rates varied from 1.22 mg/min to 25.0 mg/min.. Only one patient was considered intolerant to higher-dosing SFGC after having pruritus after a second 250-mg dose of SFGC. Three patients had nonserious events that did not preclude further dosing of SFGC.. Administration of 250 mg SFGC over 1 hour is safe and well tolerated. Individual doses of 375 mg and 500 mg SFGC also were well tolerated, but further research and experience are needed to confirm the safety and tolerance of these doses.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Population Surveillance; Treatment Outcome

Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.. This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.. A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.. SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Cross-Over Studies; Double-Blind Method; Female; Ferric Compounds; Humans; Hypotension; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Prospective Studies; Renal Dialysis

Intravenous infusion of sodium ferric gluconate (Ferrlecit) has been reported to be effective and safe in pediatric and adult hemodialysis patients with iron depletion. We sought to expand on the previous studies by treating 13 consecutive pediatric renal failure and renal transplant patients with sodium ferric gluconate doses that were higher than previously reported. Efficacy was defined as: (1) an increase in hematocrit of > or = 3 vol% with no change or a decrease in erythropoietin dose or (2) a stable hematocrit with a decrease of > or = 25% in the erythropoietin, 2 weeks to 2 months after sodium ferric gluconate infusion. Two dosing strategies were employed: (1) high dose, where single dose sodium ferric gluconate (mg) approximately calculated iron deficit, and (2) sodium ferric gluconate, 62.5 mg/dose for children < 40 kg, 125 mg/dose for children > 40 kg, infused on eight consecutive hemodialysis runs. There was only one self-limited adverse reaction in 60 doses. Three patients with previous adverse reactions to iron dextran tolerated sodium ferric gluconate without adverse effect. Sodium ferric gluconate was efficacious in eight out of ten patients that received a cumulative dose > 5 mg/kg. The mean hematocrit increased 30.3 +/- 7.8 to 36.4 +/- 4.4 vol% (P = 0.04) and the mean erythropoietin dose decreased 251.5 +/- 149.1 to 100.7 +/- 113.0 units/kg/week (P = 0.02). Although sodium ferric gluconate appears to be effective and safe at the doses used, multicenter, prospective pharmacokinetic and clinical trials of sodium ferric gluconate should be conducted in children.

Topics: Adolescent; Adult; Child; Double-Blind Method; Female; Ferric Compounds; Hematocrit; Humans; Iron; Iron Deficiencies; Kidney Failure, Chronic; Kidney Transplantation; Male; Renal Dialysis

The evolution of body iron stores was prospectively analyzed during a stable erythropoiesis period in 27 subjects (14 males and 13 females) on hemodialysis for more than 2 years in order to clarify the iron requirements of these patients and the effectiveness and safety of the administration of sodium ferric gluconate as a method to maintain adequate body iron stores. All patients had a stable hemoglobin level (variation < 1 g/dl). Sixteen subjects were on maintenance recombinant human erythropoietin therapy at regular doses. All patients received intravenous sodium ferric gluconate for 6 months (62.5 mg/month). The iron requirements were estimated as the difference between the amount of iron administered and the variation of body iron stores (calculated by the empirical formula of Cook and coworkers). The hemoglobin remained stable (basal 10.7 +/- 1.1, at 6th month 10.6 +/- 1 g/dl). Considering all cases, there were no significant variations in body iron stores (basal 457 +/- 273, at 6th month 451 +/- 316 mg). The patients were classified into three groups according to whether their body iron stores decreased (group A, n = 8), remained stable (group B, n = 11), or increased (group C, n = 8). There were no differences among groups concerning sex, age, time on hemodialysis, or erythropoietin therapy. However, there were statistically significant differences concerning their basal body iron stores (group A 457 +/- 228 mg. group B 563 +/- 146, and group C 230 +/- 297 mg; p < 0.05, analysis of variance). The iron needs, considering the total group, were 2.12 +/- 2 mg/day. There were no differences in iron requirements according to sex, but menstruating women had higher iron needs than the nonmenstruating ones (4.29 +/- 2 vs. 2.08 +/- 1.45 mg/day; p < 0.01). The iron requirements in patients on erythropoietin therapy were higher than in those without (2.63 +/- 1.59 vs. 1.88 +/- 1.68 mg/day; p < 0.05). However, excluding the menstruating women, the iron need in patients on erythropoietin were similar to those in subjects without this treatment (2.16 +/- 1.13 vs. 1.88 +/- 1.68 mg/day). All patients showed good compliance with an excellent tolerance. We have observed that in subjects on maintenance erythropoietin therapy, the iron requirements are stable. The administration of sodium ferric gluconate is safe and efficient in maintaining adequate body iron stores.

Topics: Adult; Aged; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases.. Patients initiating HD between 1998 and 2008 were extracted from Taiwan's National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders.. A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75-1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load.. We found that intravenous iron supplementation did not increase short-term infection risk among HD patients.

Topics: Administration, Intravenous; Adult; Aged; Bacterial Infections; Cohort Studies; Cross-Over Studies; Databases, Factual; Diabetes Mellitus; Epidemiologic Methods; Female; Ferric Compounds; Ferric Oxide, Saccharated; Heart Failure; Hematinics; Humans; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Lung Diseases; Male; Middle Aged; Multimorbidity; National Health Programs; Renal Dialysis; Taiwan; Time Factors; Young Adult

Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex.. Retrospective cohort study of incident HD patients.. Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure.. Facility-level use of iron sucrose versus ferric gluconate.. Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths.. HRs.. We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96).. Unobserved selection bias from nonrandom treatment assignment.. Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.

Topics: Administration, Intravenous; Aged; Anemia; Cardiovascular Diseases; Cause of Death; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Proportional Hazards Models; Renal Dialysis; Retrospective Studies

Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD).. Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)].. In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups.. In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.

Topics: Administration, Intravenous; Aged; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Prognosis; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; United States

Intravenous iron supplementation is a basic principle in the therapy of haemodialysis (HD) patients with renal anaemia. In the Iron Dextran in Renal Anaemia (IDIRA) study, we analysed the efficacy of a therapy with low-molecular-weight iron dextran (LMW-ID) in stable HD patients with adequate iron stores previously treated with ferric gluconate.. IDIRA was an open-label, prospective, non-randomized, observational multicenter trial over 12 months in iron-repleted HD patients. All patients were treated with intravenous LMW-ID. Measures of efficacy were changes of haemoglobin (Hb), serum ferritin, erythropoietin dose and the response to iron therapy calculated as ferritin efficacy and Hb efficacy. Statistical analysis was done by the Wilcoxon test.. A total of 221 HD patients with a mean age 63.7 +/- 13.8 years were included. A total of 208 out of 221 patients were on erythropoietin therapy. Median time on dialysis was 2 (1-4) years. Mean Kt/V was 1.3. Of the 221 patients, 208 completed the 12-month study period. Mean Hb and serum ferritin increased without the need for higher erythropoietin doses. The mean amount of iron per week administered remained stable. Ferritin efficacy and Hb efficacy improved using LMW-ID (p < 0.01).. We conclude that LMW-ID improves anaemia management even in iron-pretreated HD patients.

Topics: Aged; Anemia; Darbepoetin alfa; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Intravenous (IV) iron is a necessary component of the anemia management plan for the hemodialysis patient. Despite the demonstrated benefits of IV iron, questions remain as to the most effective strategies for using IV iron to maintain target hemoglobin (Hb) levels, ensure adequate iron supply, and optimize erythropoiesis-stimulating agent (ESA) therapy. Significant questions also surround the extent of the serum ferritin marker to reliably guide IV iron treatment decisions. The recent Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) and DRIVE-II studies showed that improvements in Hb levels, iron status, and ESA responsiveness can be achieved with a repletion course of IV iron in patients with serum ferritin levels up to 1200 ng/mL. These studies also demonstrated that higher serum ferritin levels are a poor predictor of positive response to IV iron. We sought to apply the lessons learned from the DRIVE studies in our hemodialysis clinic. We designed this retrospective study to determine if regular, low-dose IV iron administered to patients with serum ferritin levels up to 1200 ng/mL could improve measures of anemia and iron status while optimizing the use of IV iron and ESAs.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Monitoring; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis; Retrospective Studies; Total Quality Management; Treatment Outcome

Use of parenteral iron for anemia management in dialysis patients has greatly increased. Exceeding hemoglobin target levels is not without risk, and whether parenteral iron administration contributes to exceeding targets has not been tested. The authors aimed to determine prevalence of parenteral iron administration and its contribution to exceeding hemoglobin target levels.. The authors performed a retrospective observational study of 149,292 hemodialysis patients using Centers for Medicaid & Medicare Services data. All patients were point prevalent on January 1, 2004; survived through June 30, 2004; had Medicare as primary payer; were treated with erythropoiesis stimulating agents (ESAs); and had valid hemoglobin values in April, May, and June, 2004.. Of the cohort, 58% received parenteral iron; use was more likely among men, whites, younger patients, and patients with end-stage renal disease as a result of diabetes. Age > 75 yr, African American and other races, baseline hemoglobin > 12 g/dl, higher ESA dose, and iron use in months 1 to 4 of the study period were independently associated with the risk of exceeding hemoglobin levels of 12, 13, and 14 g/dl. Receiving iron in month 4 of the study period showed the highest probability of exceeding targets (odds ratios 1.49, 1.43, 1.50 for hemoglobin levels 12, 13, 14 g/dl, respectively).. Parenteral iron use is prevalent, and although adequate iron stores are central to ESA response, iron use may contribute to exceeding recommended hemoglobin levels. Only data from a prospective trial can confirm this association.

Topics: Aged; Anemia, Iron-Deficiency; Centers for Medicare and Medicaid Services, U.S.; Drug Therapy, Combination; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Practice Guidelines as Topic; Renal Dialysis; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome; United States

In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.. The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.. Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) microg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1-202 mg/month, slightly worse with 202-455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation < or = 16%, serum ferritin < or = 100 microg/L, best with transferrin saturation > 25%, serum ferritin > 600 microg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.. Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.

Topics: Adult; Aged; Anemia; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Survival Analysis; Transferrin

Clinicians who manage anemia in patients with chronic kidney disease, both on and off dialysis therapy, face several challenges: maintain stable hemoglobin (Hb) levels in their patients, avoid overshooting Hb targets, balance intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs), and improve ESA response to use the lowest effective ESA dose. Special attention to ESA hyporesponsiveness, as well as the role of insufficient iron, is required. The efficacy of IV iron in managing these challenges, particularly in hemodialysis patients who have anemia despite adequate ESA doses, was shown in the randomized controlled Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) clinical trial and its 6-week follow-up extension study, DRIVE-II. These studies provide suggestive evidence of the ability of IV iron to reduce ESA requirements and maintain improved Hb levels in anemic hemodialysis patients with serum ferritin levels of 500 to 1,200 ng/mL and transferrin saturations of 25% or less.

Topics: Anemia; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ferric Compounds; Guidelines as Topic; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Renal Dialysis; United States; United States Food and Drug Administration

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

In vitro evidence suggests that different intravenous iron (i.v. Fe) preparations may be associated with different infection rates. This observational study was to determine if different bacteremia rates are associated with different types or amounts of i.v. Fe preparations.. This retrospective, single-center study was carried out from April 2001 November 2002, a period in which a global switch from ferric gluconate (FG) to iron sucrose (IS) occurred. During Period I (April 2001 - January 2002) FG was the only i.v. Fe administered in our hemodialysis unit. During Period II (February 2002 - November 2002) IS was the only i.v. Fe administered in our unit. Group A (n = 63) received hemodialysis during both Period I and Period II. Group B (n = 41) received hemodialysis either during Period I or Period II.. More bacteremic episodes occurred while IS than while FG was being administered. The adjusted bacteremia incidence rate ratios (IRRs) associated with use of IS vs. FG were 2.92 (95% CI, 1.01 - 8.5) and 2.84 (95% CI 1.32 - 6.09) in Groups A and B, respectively. The adjusted bacteremia IRRs associated with receiving > 2,000 mg of i.v. Fe were 2.42 (95% CI 1.03 - 5.6) and 1.54 (95% CI 0.43 - 5.69) in Groups A and B, respectively. Use of catheters as hemodialysis access increased bacteremia risk in both groups.. Use of iron sucrose is associated with higher bacteremia rates than ferric gluconate. The potential association between the cumulative amount of i.v. Fe administered and bacteremia risk is unclear. Randomized clinical trials are needed to verify our findings.

Topics: Aged; Anemia, Iron-Deficiency; Bacteremia; Chi-Square Distribution; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Poisson Distribution; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Statistics, Nonparametric

Topics: Ferric Compounds; Gluconates; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Renal Dialysis

Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration.. Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil respiratory burst was assessed by luminol-enhanced chemiluminescence (CL). Plasma advanced oxidation protein products (AOPP) concentration was measured spectrophotometrically. During the second and the fourth HD, 62.5 mg of sodium ferric gluconate was applied IV in the 65th minute of HD. Before the last two HD, the patients were given orally 200 mg of vitamin E daily for 7 days. Patient's results were compared with healthy controls.. Predialysis CL is higher in patients than in controls (1,926 +/- 436 vs. 1,083 +/- 325 RLU, p<.01). CL decreases in the 60th min of HD (1,926 +/- 436 vs. 1,220 +/- 599 RLU, p<.05); thereafter, it remains stable. After Fe application, CL increases at time 130 compared with CL at time 60 (1,303 +/- 269 vs. 877 +/- 292 RLU, p<.05). AOPP concentration is higher in patients than in controls (137.5 +/- 42.7 vs. 88.9 +/- 24.8 micromol/L, p<.01) and remains unaffected by vitamin E supplementation. After vitamin E intake, predialysis CL remains significantly higher than in controls, and changes in CL during HD are minimal despite Fe administration.. HD patients' neutrophils generate more oxygen radicals than in healthy individuals. This production decreases during HD and then increases after IV Fe administration. Short-term vitamin E administration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress.

Topics: Administration, Oral; Aged; Biocompatible Materials; Case-Control Studies; Female; Ferric Compounds; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Luminescent Measurements; Male; Membranes, Artificial; Middle Aged; Oxidative Stress; Renal Dialysis; Respiratory Burst; Vitamin E

Topics: Ferric Compounds; Humans; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.

Topics: Adult; Alcohol Oxidoreductases; Anemia, Iron-Deficiency; Biomarkers; Drug Administration Schedule; Erythrocytes; Female; Ferric Compounds; Follow-Up Studies; Glutathione Peroxidase; Humans; Immunoenzyme Techniques; Injections, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Spectrophotometry; Superoxide Dismutase; Transferrin; Treatment Outcome

Two new intravenous (IV) iron products, ferric gluconate and iron sucrose, recently were approved for use in the United States. We report trends in IV iron use in both incident (1994 to 2001) and prevalent (1994 to 2002) Medicare US dialysis patients.. Included patients had Medicare as a primary payer. Recombinant human erythropoietin doses, IV iron use, and hemoglobin data were obtained from Medicare outpatient files. The most recent cohorts included 241,770 prevalent hemodialysis (HD) patients in 2002 and 11,744 incident HD patients in 2001.. For incident HD patients in the first 9 months of dialysis therapy, the percentage of patients administered IV iron increased sharply between 1994 and 1997 and then increased gradually between 1997 and 2001. In 2002, a total of 84.4% of HD and 19.3% of peritoneal dialysis (PD) patients were administered IV iron. Ferric gluconate use increased slowly in 2000, increased from 5.7% to 18.6% from December 2000 to January 2001, increased to 29.8% in April 2002, and was 23.3% in December 2002. Iron sucrose use increased to 26% by December 2002. The absolute monthly percentage of HD patients administered IV iron dextran decreased from 49.6% in January 2000 to 3.6% in December 2002.. In US patients with end-stage renal disease, IV iron use has increased, although slowly, from 1997 to 2002. Ferric gluconate and iron sucrose have become the predominant form of therapy. IV iron therapy was used in a much smaller percentage of PD compared with HD patients, and racial and geographic variability was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Child; Child, Preschool; Drug Utilization; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Incidence; Infant; Infusions, Intravenous; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Outpatients; Peritoneal Dialysis; Prevalence; Recombinant Proteins; Renal Dialysis; Retrospective Studies; United States

Topics: Adult; Aged; Aged, 80 and over; Ferric Compounds; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Intravenous iron is usually required to optimize the correction of anaemia in persons with advanced chronic kidney disease and end-stage renal disease. Randomized clinical trials may have insufficient power to detect differences in the safety profiles of specific formulations.. We obtained data from the US Food and Drug Administration on reported adverse drug events (ADEs) related to the provision of three formulations of intravenous iron during 1998-2000. We estimated the relative risks [odds ratios (OR)] of ADEs associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran using 2 x 2 tables.. The total number of reported parenteral iron-related ADEs was 1981 among approximately 21,060,000 doses administered, yielding a rate of 9.4 x 10(-5), or approximately 94 per million. Total major ADEs were significantly increased among recipients of higher molecular weight iron dextran (OR 5.5, 95% CI 4.9-6.0) and sodium ferric gluconate complex (OR 6.2, 95% CI 5.4-7.2) compared with recipients of lower molecular weight iron dextran. We observed significantly higher rates of life-threatening ADEs, including death, anaphylactoid reaction, cardiac arrest and respiratory depression among users of higher molecular weight compared with lower molecular weight iron dextran. There was insufficient power to detect differences in life-threatening ADEs when comparing lower molecular weight iron dextran with sodium ferric gluconate complex.. Parenteral iron-related ADEs are rare. Using observational data, overall and most specific ADE rates were significantly higher among recipients of higher molecular weight iron dextran and sodium ferric gluconate complex than among recipients of lower molecular weight iron dextran. These data may help to guide clinical practice, as head-to-head clinical trials comparing different formulations of intravenous iron have not been conducted.

Topics: Ferric Compounds; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Odds Ratio; Renal Dialysis

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease patients. Therefore it is essential that serum ferritin levels should be maintened > 200 micro g/l. Functional iron deficiency occurs with serum ferritin levels > 200 micro g/l and transferrin saturation (TFS) lower than 20 %. The purpose of this study was to determine the efficacy of iron therapy in dialysis patients with serum ferritin levels higher than 200 micro g/l.. A total of 16 stable patients receiving chronic hemodialysis completed a 6-month survey period. Hemodialysis therapy and weekly subcutaneous rhEPO dose remained unchanged. Patients were divided into three groups according to their TFS, with TFS low (<20 %), barely adequate (20 % < TFS < 25 %) or optimal (>30 %). Sodium ferric gluconate complex (62.5 mg iron) was administered once per week intravenous over 10 minutes at the end of the dialysis.. After 3 months, hemoglobin was significantly higher in all groups (10.3 +/- 0.7 g/dl to 12,6 +/- 1.3 g/dl; p < 0,01) with no difference between the three groups and was constant in the following 3 months. Intravenous iron therapy raised ferritin levels significantly after 3 and 6 months: this observation was similar in all groups. The rise in TFS varied between and within the three groups.. Consistent intravenous iron therapy in combination with subcutaneous rhEPO had a rapid effect on the correction of anemia in patients with even optimal serum ferritin levels receiving chronic hemodialysis. There was no difference between patients with low, barely adequate and optimal TFS. It is concluded that there is a need for consistent intravenous iron therapy also in hemodialysis patients with optimal serum ferritin levels to correct anemia.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin; Treatment Outcome

Although maintenance of iron stores by intravenous iron infusion has become increasingly common in chronic hemodialysis patients, the effects of intravenous iron on blood pressure are not clear.. In 52 mostly African-American patients in an urban setting, we reviewed blood pressure data over the course of hemodialysis on days that intravenous iron was administered and on control days.. The drop in blood pressure from the beginning to the end of hemodialysis was more pronounced when iron was not administered (9.9 +/- 1.2 mm Hg) compared to when iron was administered (4.1 +/- 1.7 mm Hg; p < 0.01). In a subset of chronic hemodialysis patients, blood pressure was actually higher at the end of hemodialysis compared to at the onset (9.6% of control hemodialysis sessions and 32.7% of sessions in which iron was administered; p < 0.01). The incidence of intra-dialytic hypotension and related symptoms was similar on iron and non-iron days.. Intravenous iron therapy, well entrenched in clinical practice for the treatment of the anemia of end-stage renal disease, may reduce the incidence and magnitude of post-dialytic hypotension.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Pressure; Female; Ferric Compounds; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Topics: Aged; Aged, 80 and over; Anemia; Cost-Benefit Analysis; Drug Costs; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Spain; Sucrose

Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO).. The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition.. A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment.. The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Topics: Aged; Anemia; Biomarkers; C-Reactive Protein; Epidemiologic Methods; Erythropoietin; Female; Ferric Compounds; Humans; Inflammation; Interleukin-6; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Male; Malnutrition; Middle Aged; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Sex Factors; Syndrome; Tumor Necrosis Factor-alpha

Identical National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) hematologic and iron targets apply to chronic kidney disease (CKD), peritoneal dialysis (PD), and hemodialysis (HD) patients, yet intravenous (i.v.) nondextran iron therapy is FDA approved only in HD patients. This is because oral iron has been considered adequate in CKD and PD patients, and delivering a parenteral therapy on a frequent basis to an outpatient population with notoriously poor vascular access presents logistical complexities. However, recognition of the need for more aggressive treatment of anemia in the CKD and PD population is growing. This awareness, along with the improved safety profiles of the new, nondextran irons, is tipping the risk-benefit ratio toward more widespread use of i.v. iron in these patients. This article provides a summary of the literature and of our own experience using i.v. iron therapy in CKD and PD patients. Our protocol relies on early monitoring and intervention with i.v. ferric gluconate before severe iron deficiency develops. The proactive approach allows for relatively infrequent treatments at only moderately "high" doses (250 mg) of ferric gluconate. The convergence of convenience and safety may expedite more energetic anemia prevention and treatment in PD and CKD patients.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis

Ferric gluconate complex in sucrose (Ferrlecit) has been associated with less side-effects than iron dextran; however, the recommended dose of 62.5-125 mg per treatment is only suitable for haemodialysis (HD) patients. We retrospectively analysed the incidence of the side-effects associated with a high dose of Ferrlecit infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3-4 h, and 10 treatments of 500 mg/5 h infusion). The patients were in the age range of 32-75 years old, seven with chronic renal failure (CRF), and six on dialysis treatment. One (10%) of the 10 treatments using a 250 mg dose was complicated with severe nausea/vomiting, diarrhoea and a burning sensation in the feet. Three (30%) of the 10 treatments using a 500 mg dose were complicated with: chills, severe nausea/vomiting, hypotension and syncope in one; severe nausea/vomiting, diarrhoea and hypotension in one; and an episode of vomiting in one patient. A single treatment with a 250 mg dose resulted in no significant change in haematological parameters. A single treatment with a 500 mg dose resulted in a significant increase in haemoglobin (Hgb) and haematocrit (Hct), but only a rising trend in serum iron,% transferrin saturation and ferritin pre versus 1-2 months postinfusion. In conclusion, Ferrlecit doses of 250 or 500 mg are complicated with significant untoward reactions in 10-30% of patients, in a dose-dependent fashion.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Female; Ferric Compounds; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Severity of Illness Index

We hypothesized that intravenous iron will improve hemoglobin (Hgb) concentrations in anemic patients with chronic kidney disease (CKD), and the response would be greater if the underlying erythropoietin deficiency also was treated.. Charts of 58 CKD veterans (glomerular filtration rate < 80 mL/min) administered at least 125 mg of sodium ferric gluconate complex in sucrose (SFGC) during a period of 1 year for the primary outcome of an increase in Hgb level by at least 0.5 g/dL were reviewed.. Mean Hgb level at baseline was 10.5 +/- 1.4 (SD) g/dL (105 +/- 14 g/L) in the 30 patients administered recombinant human erythropoietin (rHuEPO) plus SFGC and 10.1 +/- 1.3 g/dL (101 +/- 13 g/L) in the 28 patients administered SFGC alone (P = not significant). The primary event occurred in 83% of the rHuEPO-plus-SFGC group at 31 days compared with 60% at 62 days in the group administered SFGC alone (P = 0.037, Cox F test). In patients administered SFGC alone, mean maximal Hgb level was 11.4 +/- 0.9 g/dL (114 +/- 9 g/L) in contrast to 12.4 +/- 1.7 g/dL (124 +/- 17 g/L) in the combination group, which remained significantly different even after adjustment for biologically important covariates (P = 0.01, analysis of covariance). Of the 240 doses of SFGC administered for which infusion records were available, 237 doses were well tolerated; three hypotensive episodes occurred in 2 patients, which did not result in discontinuation of the drug in either case.. Correction of anemia with parenteral iron alone suggests a high prevalence of iron deficiency in patients with CKD. Treatment of concomitant iron deficiency with SFGC was well tolerated in patients with CKD and appears to optimize management of anemia.

Topics: Administration, Oral; Aged; Anemia, Iron-Deficiency; Clinical Pharmacy Information Systems; Databases as Topic; Drug Administration Schedule; Erythropoietin; Female; Ferric Compounds; Glomerular Filtration Rate; Humans; Hypotension; Iron; Kidney Failure, Chronic; Male; Medical Records; Recombinant Proteins; Retrospective Studies; Sucrose; Treatment Outcome; Veterans

Multiple parenteral iron (Fe) formulations exist for administration to patients with end-stage renal disease. Although there are concerns regarding their potential toxicities, no direct in vitro comparisons of these agents exist. Thus, the present study contrasted pro-oxidant and cytotoxic potentials of four available Fe preparations: Fe dextran (Fe dext), Fe sucrose (Fe sucr), Fe gluconate (Fe gluc), and Fe oligosaccharide (Fe OS).. Differing dosages (0.06 to 1 mg/mL) of each compound were added to either (1) isolated mouse proximal tubule segments, (2) renal cortical homogenates, or (3) cultured human proximal tubule (HK-2) cells (0.5- to 72-hour incubations). Oxidant injury (malondialdehyde generation) and lethal cell injury (percentage of lactate dehydrogenase release; tetrazolium dye uptake) were assessed. Effects of selected antioxidants (glutathione [GSH], catalase, dimethylthiourea (DMTU), and sodium benzoate also were assessed.. Each test agent induced massive and similar degrees of lipid peroxidation. Nevertheless, marked differences in cell death resulted (Fe sucr >> Fe gluc > Fe dext approximately Fe OS). This relative toxicity profile also was observed in cultured aortic endothelial cells. Catalase, DMTU, and sodium benzoate conferred no protection. However, GSH and its constituent amino acid glycine blocked Fe sucr-mediated cell death. The latter was mediated by mitochondrial blockade, causing free radical generation and a severe adenosine triphosphate depletion state.. (1) parenteral Fes are highly potent pro-oxidants and capable of inducing tubular and endothelial cell death, (2) markedly different toxicity profiles exist among these agents, and (3) GSH can exert protective effects. However, the latter stems from GSH's glycine content, rather than from a direct antioxidant effect.

Topics: Animals; Aorta; Cell Division; Cell Line; Cell Line, Transformed; Cell Survival; Chlorides; Endothelium, Vascular; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Kidney Tubules, Proximal; Lipid Peroxidation; Male; Malondialdehyde; Mice; Oligosaccharides; Oxidants; Parenteral Nutrition

Topics: Drug Hypersensitivity; Female; Ferric Compounds; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Middle Aged; Pruritus

This is not a controlled study but an anecdotal experience that resulted in improved outcomes in a patient with multiple allergies, including iron dextran. Target Hct/Hgbs were attained and exceeded, although iron indices were not fully achieved. Infections demonstrated RE blockade and failure of TSAT to reach target range. The multidisciplinary team's successful decision to trial SFG in a medically complex patient allowed profound iron deficiency to be treated safely and effectively, which was not possible prior to the availability of an alternate iron preparation. It is rewarding to have the option to offer a medication that improves patients' status and enhances outcomes. Mr. C. was less tired and had more energy following his first and subsequent courses of therapy. "I couldn't believe how tired I was without realizing it until after I finished a course of iron therapy. I just thought that was my quality of life on dialysis. It's much better now and I have more energy." Such comments justify our efforts on our patients' behalf.

Topics: Adult; Anemia, Iron-Deficiency; Drug Combinations; Drug Hypersensitivity; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Patient Care Planning; Renal Dialysis; Sucrose; Treatment Outcome

Hemodialysis (HD) patients are prone to develop iron deficiency because of consumption of iron stores during erythropoietin (EPO) therapy. Data are needed to establish the factors involved in the different iron needs among these patients. Sixty-five HD patients were prospectively studied during a year. The subjects were dialyzed through polytetrafluoroethylene (PTFE) grafts (n = 23), arteriovenous native fistulae (n = 41), and a Permcath (n = 1). Twenty-four patients were administered aspirin; 23 patients, ticlopidine; 1 patient, dipyridamole; and 4 patients, anticoagulation with acenocoumarol. Iron supplementation (oral or parenteral) and laboratory parameters were recorded monthly. Significant differences in iron requirements, depending on the use of antiplatelet and/or anticoagulation agents, were found. Total parenteral iron supplements were greater in patients on antiplatelet therapy with either native or graft vascular accesses compared with the rest (2,406 +/- 1,445 versus 1,562 +/- 858 mg; P = 0.0081). Twelve of 52 patients on antiplatelet therapy required oral iron and only 1 of 13 patients not on antiplatelet therapy was administered oral iron supplements (P < 0.05). Patients on antiplatelet therapy were administered more transfusions (1.9 +/- 3.8 transfusions/y) than individuals not on antiplatelet therapy (0.15 +/- 0.3 transfusions/y; P = 0.0015). However, only patients with PTFE grafts on antiplatelet therapy had a post-HD bleeding time longer than patients not on antiplatelet therapy (9.1 +/- 3.6 versus 5.7 +/- 3.9 minutes; P < 0.0001). Multiple logistic regression analysis showed that the use of antiplatelet agents (P < 0.05) is an independent factor that increased the probability of requiring greater parenteral iron supplements (>2.5 g/y). Patients with PTFE grafts required more EPO than those with autologous fistulae (160 +/- 93 versus 100 +/- 63 U/kg/wk; P = 0.012). No differences between groups were found that could explain this finding. Antiplatelet and/or anticoagulation therapy implied the use of greater amounts of iron supplements in HD patients. Although these greater requirements of iron occurred in parallel with bleeding from the vascular access, additional data favor the existence of other factors, eg, interdialytic blood losses. The present study suggests that antiplatelet therapy may be an important factor in determining iron requirements in HD patients. Moreover, our data relate for the first time the use of prosthetic grafts

Topics: Administration, Oral; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis Implantation; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Humans; Infusions, Parenteral; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Requirements; Platelet Aggregation Inhibitors; Prospective Studies; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Ferric Compounds; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Topics: Case-Control Studies; Female; Ferric Compounds; Humans; Iron; Iron Metabolism Disorders; Kidney Failure, Chronic; Male; Renal Dialysis

Zinc protoporphyrin (ZPP), a metabolic intermediate generated in the red blood cell by incorporation of zinc instead of iron, has been suggested to be a sensitive and specific parameter of absolute iron deficiency in haemodialysis (HD) patients.. We studied 62 HD patients, 29-86 years old, with ZPP levels > 50 mumol/mol haeme (normal value of ZPP < 40 mumol/mol haeme) assessing the value of ZPP as a marker of functional iron deficiency at different cut-off points of ZPP. None of the patients had apparent inflammatory disease, infectious disease, or malignancy. ZPP, haemoglobin, iron and ferritin levels were determined before, and after a 24-week period of once-weekly i.v. administration of 40 mg iron, to determine whether ZPP levels return to normal during adequate iron supplementation (960 mg iron/ patient).. There was no significant change in ZPP levels after iron supplementation in patients with a ZPP > 50 mumol/mol haeme (96.7 +/- 49.8 versus 88.4 +/- 43.5 mumol/mol haeme before and after iron administration respectively, P = n.s.). However, in patients with a ZPP > 90 mumol/mol haeme, there was a significant reduction in ZPP levels (141.2 +/- 54.5 versus 108.0 +/- 48.8 mumol/mol haeme, P < 0.001). Serum ferritin increased significantly in both groups. There was no correlation between ZPP and serum ferritin at any time during the study. There was also no correlation between serum aluminium levels and ZPP and no significant difference in changes in ZPP in patients receiving desferrioxamine therapy compared to those not receiving desferrioxamine therapy. We did find a significant correlation between moderately elevated total blood lead concentrations and ZPP levels at the end of the study. The ZPP levels were not significantly different in the range from 50-110 mumol/mol haeme before and after i.v. iron supplementation in the responders (10% increase of haemoglobin or 20% decrease of the recombinant human erythropoietin dose) compared with the non-responders.. Our data indicate that ZPP cannot be used to predict the erythropoietic response to iron supplementation. However, ZPP levels may be an indicator of functional iron deficiency due to blockade of the reticuloendothelial iron release in haemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Enzyme Inhibitors; Erythrocytes; Erythropoiesis; Female; Ferric Compounds; Ferritins; Heme Oxygenase (Decyclizing); Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Protoporphyrins; Regression Analysis; Renal Dialysis

Erythropoietin (Epo) is an effective but expensive treatment for anaemia in patients with chronic renal failure. Hyporesponsiveness to Epo, particularly in haemodialysis patients, is most commonly due to a functional iron deficiency, which is difficult to monitor reliably.. Forty-six stable haemodialysis patients, receiving Epo therapy, were commenced on regular low-dose intravenous iron (sodium ferric gluconate complex) at a dose of 62.5 mg/5 ml given as a slow injection post-dialysis twice weekly, weekly, or fortnightly, according to their serum ferritin levels. Haemoglobin, serum ferritin, Epo dose, and iron dose were measured at 6-weekly intervals over a 6-month period.. At the beginning of the study, 12 patients in the group had ferritin levels of less than 100 microg/l, and were thus considered to potentially have an absolute iron deficiency. The study group was therefore split into two subgroups for the purpose of analysis, i.e. the 12 patients with ferritin levels of less than 100 microg/l at the start of the study or 'low ferritin group', and the remaining 34 patients with ferritin levels of greater than 100 microg/l at the start of the study or 'normal ferritin group'. In the low ferritin group (n=12), intravenous iron therapy increased serum ferritin levels, and produced a significant rise in haemoglobin, and a significant reduction in Epo dose. (Ferritin pre-iron, median (range) 68 (20-96) microg/l; post-iron, 210.5 (91-447) microg/l, P<0. 003, Wilcoxon. Haemoglobin pre-iron, 10.05 (8.2-11.9) g/dl; post-iron, 11.0 (9.9-11.9) g/dl, P<0.03. Epo dose pre-iron, 9000 (4000-30 000)-i.u./week, P<0.05). Similar results were obtained in the normal ferritin group (n=34) following intravenous iron therapy, with significant increases in serum ferritin levels and haemoglobin concentrations, and a significant reduction in Epo dose. (Ferritin pre-iron, 176 (103-519) microg/l; post-iron, 304.5 (121-792) microg/l, P<0.0001. Haemoglobin pre-iron, 9.85 (6.5-12.8) g/dl; post-iron: 11.25 (9.9-13.3) g/dl, P<0.0001. Epo dose pre-iron, 6000 (2000-15 000) i.u./week; post-iron, 4000 (0-15 000)-i.u./week, P<0. 005).. Regular intravenous iron supplementation in haemodialysis patients improves the response to Epo therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Drug Synergism; Erythropoietin; Female; Ferric Compounds; Ferritins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The influence of body iron stores on the concentration of serum erythropoietin was studied in 48 hemodialyzed patients not receiving human recombinant erythropoietin, androgens or iron supplements. The serum erythropoietin concentration was 11.6 +/- 10.4 mIU/ml. There was no correlation between the serum erythropoietin and the hematocrit or hemoglobin concentration; however, there was a correlation between the serum erythropoietin and the log of serum ferritin (r = -0.5699, p < 0.01). Serum erythropoietin levels were higher in the 18 ferropenic patients (serum ferritin < 50 ng/ml) than in the 30 patients with normal serum ferritin concentration (18 +/- 13.8 vs. 7.8 +/- 4.7 mIU/ml, p < 0.01). The administration of intravenous iron to the ferropenic patients resulted in a reduction in serum erythropoietin independent of the response of the anemia (18 +/- 13.8 basal and 7.9 +/- 6.5 mIU/ml at 4 weeks, p < 0.01). Our data would suggest that the concentration of erythropoietin in hemodialyzed patients is influenced by the serum ferritin level.

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Uremia