ferric-oxide--saccharated and Kidney-Diseases

Serious adverse events that occur with the administration of iron dextran are due to the high molecular weight preparations. Conclusions that iron sucrose and ferric gluconate are safer than iron dextran may be premature. Published literature comparing safety profiles of available parenteral iron products is reviewed. Administration of iron salts to pre-dialysis patients with chronic kidney disease may not be optimal. We recommend the total dose infusion of low molecular weight iron dextran as an option for iron replacement.

Topics: Chronic Disease; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Parenteral; Iron-Dextran Complex; Kidney Diseases

Several parenteral iron preparations are now available. This article focuses on iron sucrose, a hematinic, used more widely than any other for more than five decades, chiefly in Europe and now available in North America. Iron sucrose has an average molecular weight of 34 to 60 kd, and after intravenous (IV) administration, it distributes into a volume equal to that of plasma, with a terminal half-life of 5 to 6 hours. Transferrin and ferritin levels can be measured reliably 48 hours after IV administration of this agent. Iron sucrose carries no "black-box" warning, and a test dose is not required before it is administered. Doses of 100 mg can be administered over several minutes, and larger doses up to 300 mg can be administered within 60 minutes. The efficacy of iron sucrose has been shown in patients with chronic kidney disease (CKD) both before and after the initiation of dialysis therapy. Iron sucrose, like iron gluconate, has been associated with a markedly lower incidence of life-threatening anaphylactoid reactions and may be administered safely to those with previously documented intolerance to iron dextran or iron gluconate. Nonanaphylactoid reactions, including non-life-threatening hypotension, nausea, and exanthema, also are extremely uncommon with iron sucrose. Management of patients with the anemia of CKD mandates that we carefully examine the effectiveness and safety of this oldest of iron preparations and the accumulating present-day data regarding it and contemporaneous agents.

Topics: Chronic Disease; Drug Administration Schedule; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Diseases; Treatment Outcome

Saccharaed ferric oxide (SFO)-induced osteomalacia develops when excessive SFO infusions are administrated to patients with anemia for prolonged periods for a few years. The small particles and almost neutral saccharide of SFO filter through the glomerular tufts into the renal tubules, resulting in impairment of proximal renal tubular function, particularly renal reabsorption of phosphate and 1alpha-hydroxylase activity, resulting in decreased serum levels of phosphorus and active vitamin D, both of which lead to development of hypophosphatemic osteomalacia. Furthermore, SFO, at concentrations attainable in serum, exacerbates the osteomalacia by inhibiting bone formation directly. In contrast to itai-itai disease, another iatrogenic osteomalacia due to cadmium nephropathy [44], the proximal renal tubular function impairment induced by SFO is reversible simply by discontinuing the nephrotoxin, which is followed by improvement of all the clinical manifestations, except bone deformities. So far, SFO-induced osteomalacia, that is, SFO-induced osteopathy due to nephropathy, has been reported only in Japan, probably due to the lax surveillance system of the health insurance scheme. All physicians who prescribe SFO should be aware of its severe adverse effects. We hope that such iatrogenic osteomalacia caused by abusive infusion of SFO will never again be reported in our country.

Topics: Aged; Anemia, Iron-Deficiency; Anemia, Refractory; Animals; Calcitriol; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Iatrogenic Disease; Kidney Diseases; Male; Middle Aged; Osteomalacia; Phosphates

Among patients with chronic kidney disease (CKD), differences in proteinuria are seen between intravenous iron preparations after a single dose exposure. This study examined differences in proteinuria between two intravenous iron preparations after multiple doses.. Patients with iron-deficiency anemia and CKD, stratified by angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor-blocker (ARB) use, were randomized to iron sucrose or ferric gluconate. Each patient at 12 centers received 100 mg of study drug weekly for 5 weeks. Urine protein/urine creatinine ratio was measured before each dose and frequently thereafter for 3 hours.. Postbaseline data were available from 33 patients receiving iron sucrose and 29 patients receiving ferric gluconate. Although neither preparation of intravenous iron increased the predose level of proteinuria, the proteinuric response to intravenous iron was dependent on the type of iron and ACEI/ARB use. Without ACEIs/ARBs, ferric gluconate tended to cause less proteinuria with repeated iron administration; iron sucrose did not mitigate or aggravate proteinuria. Among patients receiving ACEIs/ARBs, in contrast to ferric gluconate, which produced only mild transient proteinuria, iron sucrose produced a consistent and persistent proteinuric response that was on average 78% greater.. Although multiple doses of either intravenous iron did not increase basal levels of proteinuria, postdose proteinuria was greater with iron sucrose than with ferric gluconate. These data suggest that nephrotoxicity of iron may depend on type of intravenous iron and on ACEI/ARB use. The long-term effects on kidney function need to be further evaluated.

Topics: Adult; Aged; Albuminuria; Anemia, Iron-Deficiency; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Creatinine; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria

An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD).. One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment.. Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups.. Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L.

Topics: Administration, Oral; Aged; Anemia; Chronic Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrous Compounds; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Severity of Illness Index

Patients with iron deficiency anaemia (IDA) in the setting of non-dialysis-dependent chronic kidney disease (NDD-CKD) may benefit from treatment with intravenous (IV) iron. Ferric carboxymaltose (FCM) is a novel IV iron formulation designed to permit larger infusions compared to currently available IV standards such as Venofer(R) (iron sucrose).. The primary objective of REPAIR-IDA is to estimate the cardiovascular safety and efficacy of FCM (two doses at 15 mg/kg to a maximum of 750 mg per dose) compared to Venofer(R) (1000 mg administered as five infusions of 200 mg) in subjects who have IDA and NDD-CKD. REPAIR-IDA is a multi-centre, randomized, active-controlled, open-label study. Eligible patients must have haemoglobin (Hgb) < or = 11.5 g/dL and CKD defined as (1) GFR < 60 mL/min/1.73 m(2) on two occasions or (2) GFR < 90 mL/min/1.73 m(2) and either evidence of renal injury by urinalysis or elevated Framingham cardiovascular risk score. Two thousand and five hundred patients will be randomized to FCM or Venofer(R) in a 1:1 ratio. The primary efficacy endpoint is mean change in Hgb from baseline to the highest observed Hgb between baseline and Day 56. The primary safety endpoint is the proportion of subjects experiencing at least one of the following events: death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalization, congestive heart failure requiring hospitalization or medical intervention, arrhythmias, hypertension or hypotension during the 120 days following randomization.. REPAIR-IDA will assess the efficacy and safety of two 750-mg infusions of FCM compared to an FDA-approved IV iron regimen in patients with NDD-CKD at increased risk for cardiovascular disease.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Cardiovascular Diseases; Chronic Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hemoglobins; Humans; Kidney Diseases; Male; Maltose; Middle Aged; Risk Factors; Sucrose; Treatment Outcome

Albuminuria is an excellent marker of cardiovascular and renal prognosis. Commercially available tests of immunodetectable albumin in the urine may not identify posttranslationally modified albumin that makes it undetectable to antibodies. Also, it is unclear whether albumin is degraded to smaller fragments, such as through proteolysis, in the course of acute renal injury. In 20 men with chronic kidney disease, we measured excretion rates of urinary protein (pyragallol red), immundetectable urinary albumin (immunoturbidimetry), and urinary total intact albumin (HPLC) after a single dose of 100 mg intravenous iron sucrose administered over 5 min. Fragmentation of urinary albumin and carbonylation of urinary proteins were assessed by immunoblotting. Results showed that iron infusion increased carbonylation of plasma and urinary proteins in a time-dependent manner. A transient increase in urinary excretion rates of total protein, immunodetectable urinary albumin, and total intact albumin was seen. Fragmentation and loss of immunoreactivity of albumin paralleled the changes in total protein excretion. In conclusion, fragmentation, loss of immunoreactivity, and oxidation of albumin in a time-dependent manner may underestimate the extent of injury with the immunoreactive microalbumin assay. Measurement of total intact albumin may better quantify acute renal injury.

Topics: Aged; Albuminuria; Chronic Disease; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Immunoassay; Infusions, Intravenous; Kidney; Kidney Diseases; Kinetics; Male; Oxidation-Reduction; Oxidative Stress; Proteinuria; Sensitivity and Specificity; Serum Albumin

Intravenous iron supplementation is an integral part of the management of anemia in patients with chronic kidney disease. Traditionally, this has been administered as an infusion over 1 or more hours, which requires the use of intravenous fluids and administration tubing, along with extra demands on patient and nursing time.. We prospectively investigated the safety and practicality of administering iron sucrose, 200 mg, as a bolus injection over 2 minutes in patients with chronic kidney disease. A total of 2,297 injections were administered to 657 patients. Any adverse events were recorded, including acute anaphylactoid reactions to the iron injection, along with the presence or absence of metallic taste and phlebitis, and these were classified as "serious" and "nonserious.". The most common adverse event was a mild and transient metallic taste that occurred during 412 injections (17.9%); in no case was this of significant distress to the patient. Excluding this, 2,240 injections (97.5%) proceeded uneventfully, and no case of phlebitis was recorded. Adverse events other than metallic taste were recorded in association with 57 injections (2.5%). Seven of these were caused by an acute anaphylactoid reaction to the intravenous iron. All 7 acute reactions resolved completely within 30 minutes with no sequelae, and none required hospitalization. The remaining 50 adverse events consisted of pain during the injection (n = 31), pain after the injection with or without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy (n = 4), and lightheadedness (n = 3).. Administration of 200 mg of iron sucrose as an intravenous bolus injection over 2 minutes is a practical dosing regimen in patients with chronic kidney disease, resulting in considerable savings in time and cost.

Topics: Adult; Aged; Anaphylaxis; Anemia, Hypochromic; Chronic Disease; Cohort Studies; Dysgeusia; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Graft Rejection; Humans; Hypotension; Injections, Intravenous; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies

Sodium glucose co-transporter (SGLT) 2 inhibitors are oral anti-diabetic drugs with proven kidney protective effects. Renal protective effects in non-diabetic individuals have also been shown in recent studies. The aim of this study was to determine the renal protective effects of dapagliflozin by evaluating the oxidative stress markers in the kidney tissue and demonstrating it in renal histological sections in an iron-overloaded rat model.. A total of 24 Wistar Albino rats were separated into 3 groups of 8 rats. Iron sucrose (60 ​mg/kg/day) was administered intraperitoneally to the first group (Group Fe) (n ​= ​8), iron sucrose and dapagliflozin (0.1 ​mg/kg/day) to the second group (Group Fe ​+ ​D) (n ​= ​8) and intraperitoneal saline as placebo to the control group (Group C) (n ​= ​8) for 4 weeks. The glomerular changes were semi-quantitatively scored with Oxford Classification. Oxidative stress was analyzed from the tissue fluorescent oxidation product (FLOP), malondialdehyde (MDA) and total sulfhydryl (T-SH) levels.. Dapagliflozin prevented glomerular and mesangial damage of iron overload in the non-diabetic rat model. MDA levels were significantly higher in Group Fe compared to the Group C, and there was no significant difference between the Fe ​+ ​D group and Group C. T-SH levels were preserved in the Fe ​+ ​D group and were significantly higher than in the Fe group.. The results of this study showed that dapagliflozin helped preserve the glomerular and mesangial structure histologically and reduced oxidative stress markers in a non-diabetic iron overload rat model.

Topics: Animals; Ferric Oxide, Saccharated; Glucose; Iron; Iron Overload; Kidney Diseases; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters

Experimental data suggest that iron sucrose (FeS) injection, used either alone or in combination with other prooxidants, can induce "renal preconditioning," in part by upregulating cytoprotective ferritin levels. However, the rapidity, degree, composition (heavy vs. light chain), and renal ferritin changes after FeS administration in humans remain to be defined. To address these issues, healthy human volunteers (

Topics: Acute Kidney Injury; Adult; Aged; Animals; Biomarkers; Female; Ferric Oxide, Saccharated; Ferritins; Healthy Volunteers; Humans; Infusions, Parenteral; Ischemic Preconditioning; Kidney; Kidney Diseases; Male; Mice; Middle Aged; Renal Insufficiency, Chronic; RNA, Messenger; Spleen

Iron sucrose and low-molecular-weight iron dextran (LMW-ID), two commonly used iron solutions, have been compared in terms of allergic adverse event profiles to date. However, the safety of total dose infusion of LMW-ID has been investigated by only one study in chronic kidney disease (CKD) (not dialysis) patients. Thus, we aimed to compare adverse event profiles of total and high-dose LMW-ID and iron sucrose infusions in a heterogenous renal patient group comprising CKD, hemodialysis, and peritoneal dialysis. In this retrospective chart review study, we included 110 predialysis CKD, 101 peritoneal dialysis, and 118 hemodialysis patients. We included a total of 329 patients who were administered parenteral iron sucrose or LMW-ID between September 2006 and April 2010. Adverse events were determined both by medical and nursing follow-up notes. Laboratory data and clinical characteristics were collected from patient charts. Adverse event rates were compared between iron sucrose and LMW-ID infusions. In a total of 329 patients, 530 infusions (3470 ampules) were administered. We detected adverse reaction in only 1 patient. This adverse reaction, which manifested as generalized pruritus, occurred in a patient who received 500 mg of iron sucrose infusion. There were neither anaphylactic reactions nor deaths associated with infusion of either preparation. We did not observe any other adverse event related to administration of 500 and 1000 mg of iron sucrose at single infusion. The results of this study showed comparable safety of total dose LMW-ID and high-dose iron sucrose in a heterogenous group of renal patients.

Topics: Adult; Aged; Chronic Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Hematinics; Humans; Iron-Dextran Complex; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Retrospective Studies

Anemia is iron responsive in 30 to 50% of nondialysis patients with chronic kidney disease (CKD), but the utility of bone marrow iron stores and peripheral iron indices to predict the erythropoietic response is not settled. We investigated the accuracy of peripheral and central iron indices to predict the response to intravenous iron in nondialysis patients with CKD and anemia.. A diagnostic study was conducted on 100 nondialysis patients who had CKD and anemia and were erythropoiesis-stimulating agent and iron naive. Bone marrow iron stores were evaluated by aspiration. Hemoglobin, transferrin saturation index (TSAT), and ferritin were measured at baseline and 1 month after 1000 mg of intravenous iron sucrose. Posttest predictive values for the erythropoietic response (> or =1-g/dl increase in hemoglobin) of peripheral and central iron indices were calculated.. The erythropoietic response was noted in a higher proportion in bone marrow iron-deplete than in iron-replete patients (63 versus 30%). Peripheral iron indices had a moderate accuracy in predicting response. The positive (PPV) and negative predictive values (NPV) were 76 and 72% for a TSAT of 15% and 74 and 70% for a ferritin of 75 ng/ml, respectively. In the final logistic regression model, including TSAT and ferritin, the chances of a positive response increased by 7% for each 1% decrease in TSAT.. Because an erythropoietic response is seen in half of patients and even one third of those with iron-replete stores responded whereas peripheral indices had only a moderate utility in predicting response, the therapeutic trial to intravenous iron seems to be a useful tool in the management of anemia in nondialysis patients with CKD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Blood Chemical Analysis; Bone Marrow; Bone Marrow Examination; Chi-Square Distribution; Chronic Disease; Erythropoiesis; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Iron; Kidney Diseases; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Time Factors; Transferrin; Treatment Outcome; Young Adult

Topics: Chronic Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Kidney Diseases; Male; Proteinuria; Renal Dialysis

Inflammation is a central component of progressive chronic kidney disease (CKD). Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD; however, its potential to provoke an inflammatory response is unknown. In 20 veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment was repeated at 1 week. Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for time effect). Urinary excretion peaked at 30 min and plasma concentration at 15 min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/- 67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and transient generation and/or release of MCP-1 plasma concentration and increases urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC. These results may have implications for the progression of CKD with parenteral iron.

Topics: Aged; Chemokine CCL2; Chronic Disease; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Reproducibility of Results

Topics: Animals; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron-Dextran Complex; Kidney Diseases; Kidney Tubules; Oxidative Stress

Monocyte chemoattractant protein-1 (MCP-1) promotes renal inflammation, thereby contributing to acute and chronic nephropathies. Its production is stimulated by oxidative stress. Thus, this study tested whether pro-oxidant iron/carbohydrate complexes, used to treat iron deficiency, induce MCP-1 in renal/extrarenal tissues, in plasma, and in the setting of experimental nephropathy.. CD-1 mice received 2 mg of intravenous iron [complexed with dextran (iron dextran), sucrose (iron sucrose), or gluconate (iron gluconate)]. Renal MCP-1 and/or its mRNA were measured 3 hours to 7 days post-iron injection. Iron effects on liver, lung, spleen, and heart MCP-1 mRNA, and on peritoneal lavage fluid MCP-1 concentrations were assessed. Iron pretreatment effects on MCP-1 levels in unilaterally obstructed kidneys vs. contralateral kidneys were determined. Finally, iron gluconate's influence on proximal tubule [human kidney-2 (HK-2)] cell MCP-1 levels was assessed.. Iron sucrose (the primary test agent) markedly increased plasma and renal MCP-1 levels. It also induced multiorgan MCP-1 mRNA increments (liver > spleen > kidney > lung > heart). Iron gluconate was more potent than iron sucrose; conversely, iron dextran had no discernible effect. The iron dextran and iron sucrose-induced renal MCP-1 mRNA increments ( approximately 4x) were persistent, lasting for at least 3 to 7 days. Iron gluconate raised MCP-1 levels in peritoneal lavage fluid. It also doubled MCP-1 in unilaterally obstructed kidneys (ureteral ligation) without altering contralateral (control kidney) MCP-1 content. Iron gluconate raised HK-2 cell MCP-1, implying a direct proximal tubule effect.. Iron sucrose and iron gluconate (but not iron dextran) can induce MCP-1 generation in renal and extrarenal tissues, possibly via transcriptional events. This may dramatically impact renal disease-induced MCP-1 increments. Finally, iron can increase peritoneal lavage fluid MCP-1 levels. Whether the above changes have implications for renal disease progression, and/or for peritoneal inflammation/peritoneal dialysis efficiency, are issues which may need to be addressed.

Topics: Acute Disease; Animals; Cells, Cultured; Chemokine CCL2; Ferric Compounds; Ferric Oxide, Saccharated; Gene Expression; Glucaric Acid; Gluconates; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Cortex; Kidney Diseases; Liver; Male; Mice; Mice, Inbred Strains; Oxidative Stress; Peritoneum; RNA, Messenger

Many patients require parenteral iron therapy for optimal correction of anemia, including cancer patients who require erythropoietic drugs. Available parenteral iron therapy options include iron dextran, iron gluconate, and iron sucrose. The purpose of this study is to summarize our institution's experience with parenteral iron therapy over a 5-year period, with a focus on comparative safety profiles. All patients receiving parenteral iron therapy over this period were included in the analysis. Chi-squared test and Fisher's exact test were used to compare the adverse event rates of each product. A total of 121 patients received 444 infusions of parenteral iron over this period. Iron dextran was the most commonly used product (85 patients) and iron sucrose was the least used (2 patients). Iron gluconate was used by 34 patients. Overall adverse event rates per patient with iron dextran and iron gluconate were 16.5% and 5.8%, respectively (P = .024). Premedication with diphenhydramine and acetaminophen before infusions of iron dextran reduced adverse event rates per infusion from 12.3% to 4.4% (P = .054). Test doses of iron dextran were used 88% of the time for initial infusions of iron dextran. All adverse events for all parenteral iron products were mild or moderate. There were no serious adverse events and no anaphylaxis was observed. Our results suggest that, if test doses and premedications are used, iron dextran is an acceptable product to treat iron deficiency.

Topics: Acetaminophen; Anemia, Iron-Deficiency; Diphenhydramine; Female; Ferric Compounds; Ferric Oxide, Saccharated; Gastrointestinal Hemorrhage; Glucaric Acid; Humans; Infusions, Parenteral; Iron Metabolism Disorders; Iron-Dextran Complex; Kidney Diseases; Male; Menorrhagia; Neoplasms; Premedication; Retrospective Studies; Telangiectasia, Hereditary Hemorrhagic; United States; von Willebrand Diseases

Parenteral iron administration is a mainstay of anemia management in renal disease patients. However, concerns of potential iron toxicity persist. Thus, this study was conducted to more fully gauge iron toxicologic profiles and potential determinants thereof.. Isolated mouse proximal tubule segments (PTS) or cultured proximal tubular [human kidney (HK-2)] cells were exposed to four representative iron preparations [iron sucrose (FeS), iron dextran (FeD), iron gluconate (FeG), or iron oligosaccharide (FeOS)] over a broad dosage range (0, 30 to 1000 microg iron/mL). Cell injury was assessed by lactate deyhdrogenase (LDH) release, adenosine triphosphate (ATP) reductions, cell cytochrome c efflux, and/or electron microscopy. In vivo toxicity (after 2 mg intravenous iron injections) was assessed by plasma/renal/cardiac lipid peroxidation [malondialdehyde (MDA)], renal ferritin (protein)/heme oxygenase-1 (HO-1) (mRNA) expression, electron microscopy, or postiron injection PTS susceptibility to attack.. In each test, iron evoked in vitro toxicity, but up to 30x differences in severity (e.g., ATP declines) were observed (FeS > FeG > FeD = FeOS). The in vitro differences paralleled degrees of cell (HK-2) iron uptake. In vivo correlates of iron toxicity included variable increases in renal MDA, ferritin, and HO-1 mRNA levels. Again, these changes appeared to parallel in vivo (glomerular) iron uptake (seen with FeS and FeG, but not with FeD or FeOS). Iron also effected in vivo alterations in proximal tubule cell homeostasis, as reflected by the "downstream" emergence of tubule resistance to in vitro oxidant attack.. Parenteral iron formulations have potent, but highly variable, cytotoxic potentials which appear to parallel degrees of cell iron uptake (FeS > FeG >> FeD or FeOS). That in vitro injury can be expressed at clinically relevant iron concentrations, and that in vivo glomerular iron deposition/injury may result, suggest caution is warranted if these agents are to be administered to patients with active renal disease.

Topics: Animals; Cell Line; Cytochromes c; Dose-Response Relationship, Drug; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; In Vitro Techniques; Infusions, Parenteral; Iron; Iron-Dextran Complex; Kidney; Kidney Cortex; Kidney Diseases; Kidney Tubules, Proximal; Male; Membrane Proteins; Mice; Mice, Inbred Strains; Microscopy, Electron; RNA, Messenger; Severity of Illness Index

Two patients with chronic kidney disease presented with severe anemia and iron deficiency. Because of their religious beliefs, red blood cell transfusions were not possible, and an aggressive therapeutic regimen of iron replenishment was instituted.. The regimen included epoetin, folic acid and high-dose intravenous iron sucrose infusions over multiple successive days (total dosages of 2 and 3.5 g).. The patients' iron stores were replenished and an erythropoietic response ensued subsequent to this aggressive and unique therapeutic regimen. There were no side effects observed which could be attributed to iron sucrose, and both patients stabilized and were discharged after 3 - 4 weeks.. In patients with chronic kidney disease who are severely anemic and iron-deficient and where transfusions are not possible, an aggressive regimen of multiple high-dose iron sucrose infusions may be both safe and effective.

Topics: Aged; Anemia; Chronic Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron Deficiencies; Jehovah's Witnesses; Kidney Diseases; Middle Aged; Severity of Illness Index; Time Factors

To study iron metabolism in patients on programmed hemodialysis (PH) in oral and intravenous administration of iron drugs; to compare clinical and financial results of using such drugs.. A two-stage trial studied iron metabolism in 158 PH patients on replacement therapy with erythropoetin. They received correction of iron deficiency with oral drugs (stage I) and venofer (stage II).. The study of iron metabolism has found its deficiency in 2/3 patients receiving oral iron: absolute (48%) and relative (20%). Administration of venofer led to a 2-fold increase in the number of patients with normal iron metabolism. The target Hb and Ht were achieved in 2.5 times more patients than before venofer treatment. The dose of erythpoetin in such cases was reduced by 40%. Side effects were not observed. The week cost of venofer treatment per patient was lower by 22.5$ than the cost of treatment with oral iron drugs.. Venofer correction of iron deficiency in PH patients is more effective both clinically and financially than use of oral iron preparations.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Drug Costs; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Sucrose; Treatment Outcome

Oral iron replacement therapy with Chromagen, containing ferrous fumarate, and Niferex, containing polysaccharide iron complex, can successfully maintain hematologic and iron indices in dialysis clients and demonstrated fewer adverse effects in selected clients. Their multiple ingredient dose forms, which further support erythropoiesis, and their possible decrease in distressing side effects should enhance client compliance, making these two drugs excellent alternatives to traditional iron therapies.

Topics: Administration, Oral; Anemia; Contraindications; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Glucaric Acid; Humans; Kidney Diseases; Renal Dialysis

Intravascular precipitates, comprised at least in part of iron, formed regularly in rabbits given one or more injections of a saccharated iron oxide preparation intravenously, and these lodged in numerous capillaries throughout the body, particularly those of the lungs and kidneys. Large numbers of the brownish precipitates remained in the capillaries of the renal glomeruli during the first few days following injection of the iron, but most of them disappeared after 5 to 7 days, with only moderate amounts of brown pigment remaining in the endothelial cells of the renal glomeruli. Signs of acute injury of the glomerular tufts-namely) pyknosis of some of the endothelial cells, margination of leukocytes within the glomerular capillaries, and slight proliferation of the epithelial cells-also developed some 5 to 7 days following injection of the iron, along with marked proteinuria, which proved transitory if no further injections were given. When the iron preparation was given repeatedly over prolonged intervals, however, the proteinuria persisted and became extreme, and hypoproteinemia developed, often with hypercholesterolemia and transitory edema as well. Histological studies of the kidneys of rabbits manifesting the nephrotic syndrome, as just described, disclosed that virtually all the renal glomeruli were greatly altered, mainly owing to proliferation of the epithelial cells, together with some fibrosis and atrophy. Some of the rabbits having marked proteinuria and other functional changes eventually developed azotemia following repeated injections of the iron, and several of them lost weight and died; the renal glomeruli of these animals showed changes like those just described, but the alterations were more extensive. Considered together, the findings provide evidence that the intravascular precipitates first occluded the glomerular capillaries for a period of several days following injection of the iron and then largely disappeared from them just prior to the development of morphologic signs of glomerular injury and proteinuria. Hence the possibility was considered that the intracapillary precipitates might have produced acute injury to the walls of the glomerular capllaries through the agency of anoxia. But it is plain that the findings of the present study do not disclose the essential nature of the anatomical change responsible for the proteinuria, or the means whereby this was produced. The findings as a whole were briefly considered in relation t

Topics: Animals; Capillaries; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Kidney; Kidney Diseases; Kidney Glomerulus; Nephrosis; Nephrotic Syndrome; Proteinuria; Rabbits