Update on adverse drug events associated with parenteral iron.

BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.     

Sodium ferric gluconate complex in haemodialysis patients: a prospective evaluation of long-term safety.

BACKGROUND: A previous single dose placebo-controlled double-blinded trial showed an extremely low (0.4%) intolerance rate of sodium ferric gluconate complex (SFGC) in SFGC-naive haemodialysis patients. No large prospective trials have assessed the safety of SFGC during repeated exposure in the outpatient haemodialysis setting. METHODS: Chronic haemodialysis patients completing the single-dose trial of SFGC were eligible to participate in this prospective, multicentre, open-label, long-term evaluation of SFGC, designed to record adverse events occurring up to 72 h post-dose. Patients received as many as 20 ampules (1250 mg total) of SFGC at an investigator-determined dose and rate over a 9 month evaluation period. RESULTS: Among 1412 enrolled patients at 54 centres, 1321 received 13,151 infusions of SFGC. Most doses (94.8%) were < or =125 mg and the majority were given over 10 min. Infusion rates ranged from <5 to 125 mg/min. There were no life-threatening events. Fifty-one patients (3.9%) experienced an adverse event, possibly related to SFGC. Of these, one experienced a serious event (hypotension). Five patients (0.4%) experienced an event that precluded SFGC readministration: pruritus (three), vasodilatation (one) and loss of taste (one). Among 372 patients (28.2%) receiving angiotensin-converting enzyme inhibitor (ACEI) therapy, adverse events were neither more common nor more severe than in the other patients. CONCLUSIONS: Repeated doses of SFGC are very well tolerated in haemodialysis patients. No life-threatening events were observed in over 13,000 doses administered. Administration of SFGC to patients using ACEI is safe and does not increase the incidence or severity of adverse events to SFGC.     

Hypersensitivity reactions and deaths associated with intravenous iron preparations.

BACKGROUND: Parenteral iron therapy is an accepted adjunctive management of anaemia in kidney disease. Newer agents may have fewer severe hypersensitivity adverse events (AE) compared with iron dextrans (ID). The rate of type 1 AE to iron sucrose (IS) and sodium ferric gluconate (SFG) relative to ID is unclear. We used the US Food and Drug Administration's Freedom of Information (FOI) surveillance database to compare the type 1 AE profiles for the three intravenous iron preparations available in the United States. METHODS: We tabulated reports received by the FOI database between January 1997 and September 2002, and calculated 100 mg dose equivalents for the treated population for each agent. We developed four clinical categories describing hypersensitivity AE (anaphylaxis, anaphylactoid reaction, urticaria and angioedema) and an algorithm describing anaphylaxis, for specific analyses. RESULTS: All-event reporting rates were 29.2, 10.5 and 4.2 reports/million 100 mg dose equivalents, while all-fatal-event reporting rates were 1.4, 0.6 and 0.0 reports/million 100 mg dose equivalents for ID, SFG and IS, respectively. ID had the highest reporting rates in all four clinical categories and the anaphylaxis algorithm. SFG had intermediate reporting rates for urticaria, anaphylactoid reaction and the anaphylaxis algorithm, and a zero reporting rate for the anaphylaxis clinical category. IS had either the lowest or a zero reporting rate in all clinical categories/algorithm. CONCLUSIONS: These findings confirm a higher risk for AE, especially serious type 1 reactions, with ID therapy than with newer intravenous iron products and also suggest that IS carries the lowest risk for hypersensitivity reactions.     

Chemical reactions of vitamin C with intravenous-iron formulations.

BACKGROUND: Intravenous (IV) iron is widely prescribed for patients on haemodialysis, to replace iron losses during treatment. It releases labile iron, which can induce oxidation of vitamin C and trigger oxidant damage. We examined the stability of vitamin C in the presence of IV iron compounds. We further examined in the ability of vitamin C to release iron from these compounds. METHODS: Vitamin C was measured by high-performance liquid chromatography with electrochemical detection. Iron release from iron sucrose (FeSuc) and ferric gluconate (FeGlu) was determined with the ferrozine method. RESULTS: Vitamin C, in human plasma or fetal calf serum, was oxidized in this order of reactivity: FeSuc > FeGlu > blank reaction. FeSuc and FeGlu also oxidized vitamin C when added to freshly obtained whole human blood. During a 4 h incubation in buffer, vitamin C stimulated the release of 60% of the iron content of FeSuc at p 4, with lesser amounts at pH 3, 5 and 6, and 5% release at pH 7.Vitamin C also triggered the release of iron from FeGlu, but less release was observed than with FeSuc. Using ferrozine reagent, no iron release was detected to heparinized human plasma, following addition of 500 microM concentrations of iron compounds. CONCLUSION: Each IV-iron compound can oxidize substantial amounts of vitamin C when added to plasma or whole blood. The interaction of vitamin C is accompanied by release of iron from the particle at mildly acidic pH, which may explain the ability of high-dose vitamin C to mobilize iron from storage sites for erythropoiesis.     

Economic appraisal of maintenance parenteral iron administration in treatment of anaemia in chronic haemodialysis patients

BACKGROUND.: Iron deficiency is common in haemodialysis patients and adequatesupplementation by the oral or parenteral route has been limitedby drug side-effects, absorption, and cost. Intermittent doses of intravenous iron dextran complex are recommendedin patients with inadequate iron stores despite maximal toleratedoral dose. We conducted a prospective study with economic analysisof a regular maintenance intravenous iron regimen in this groupof patients. METHODS.: Fifty patients comprising one-half of our haemodialysis populationrequired intravenous iron treatment, i.e. they failed to achievean arbitrary goal serum ferritin 100 µg/l despite maximaltolerated oral iron dose. After a loading dose of intravenousiron dextran complex (IV-FeD) based on Van Wyck's nomogram (400±300mg) they received a maintenance dose of 100 mg IV-FeD once every2 weeks. Initial goal serum ferritin was set at 100–200µg/l. If no increase in haemoglobin was achieved at thislevel, transferrin saturation was measured to assess bioavailableiron, and when less than 20%, goal serum ferritin was increasedto 200–300 µg/l. Recombinant human erythropoietin(rHuEpo) was used where needed to maintain haemoglobin in the9.5–10.5 g/l range only if ferritin requirements weremet. RESULTS.: Mean haemoglobin rose from 87.7±12.1 to 100.3±13.1g/l (P<0.001, Cl 7.7–17.9) at mean follow-up of 6 months(range 3–15 months). In patients on rHuEpo, dose per patientwas reduced from 96±59 u/kg per week to 63±41u/kg per week, repres enting a 35% dose reduction (P<0.05,Cl 1–65). An annual cost reduction of $3166 CDN was projected;however, in the first year this is offset by the cost of theloading dose of IV-FeD required at the beginning of treatment.No adverse reactions were encountered. CONCLUSIONS.: Iron deficiency is very common in our haemodialysis population,especially in those patients receiving rHuEpo. A carefully monitoredregimen of maintenance parenteral iron is a safe, effective,and economically favourable means of iron supplementation inpatients with insufficient iron stores on maximum toleratedoral supplements.     

Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients.

BACKGROUND: Reliable information on the incidence of severe reactions to iron dextran is limited. Administration of agents of resuscitation in acute anaphylaxis may serve as a marker to quantify life-threatening adverse drug reactions. METHODS: To determine the incidence of the most serious reactions to intravenous (i.v.) iron dextran, we searched the Gambro Healthcare US medical database for evidence of same-day administration of both i.v. iron dextran and parenteral adrenaline, corticosteroids or antihistamines. We confirmed each case as an iron dextran sensitivity reaction by direct inquiry. We also determined the total reported number of suspected adverse iron dextran reactions. RESULTS: During the 16 month study period, we determined that 1,066,099 doses of i.v. iron dextran were given to 48,509 patients, including 20,213 patients who had not previously received iron dextran (iron dextran na?ve). We identified seven patients who experienced reactions requiring resuscitative agents, all in response to a test dose (five patients) or first therapeutic dose (two patients), and therefore all in the iron-na?ve (incident) group. Thus, we found the incidence of iron dextran reactions requiring resuscitative agents to be 0.035% (7 out of 20,213). No reaction was fatal. In a combined group of incident and prevalent patients, we found 337 total reports of suspected adverse reactions to iron dextran, without regard to severity of reaction, yielding an overall per patient adverse drug event (ADE) rate of 0.69% (337 out of 48,509) and per exposure rate of 0.03% (337 out of 1,066,099). CONCLUSIONS: The incidence of reactions to iron dextran requiring resuscitative medications, per exposure or per patient, is approximately 0.035%. Reactions of this severity occur after either the test dose or first dose of iron dextran.     

Comparison of parenteral iron sucrose and ferric chloride during erythropoietin therapy of haemodialysis patients

Aim:   To compare the effects of i.v. iron sucrose and Fe chloride on the iron indices of haemodialysis patients with anaemia.
Methods:   One hundred and eight haemodialysis patients receiving recombinant human erythropoiesis-stimulating agent (ESA) (mean age 59.37 years) were enrolled and randomly assigned to an iron sucrose or an Fe chloride group. Iron supplements were administered at 100 mg/week during the first 4 weeks (loading dose). Ferritin and transferrin saturation (TSAT) were then measured and dose adjusted. Ninety-eight subjects completed treatment; 51 in the iron sucrose group and 47 in the Fe chloride group. Ferritin, TSAT, haematocrit (Hct), reticulocyte count, serum albumin, fractional clearance of urea (Kt/V) and intact parathyroid hormone (iPTH) were measured.
Results:   There was no significant difference in baseline characteristics between the groups. Significant differences between the groups were observed in both iron indices and ESA dosage. Hct at week 24 (31.1% vs 29.7%, P  = 0.006) and ferritin at week 20 (731.3 vs 631.7 ng/mL, P  = 0.006) in the iron sucrose group were significantly higher than in the Fe chloride group. ESA dosage used in the iron sucrose group at week 8 was significantly lower than in the Fe chloride group (244.9 vs 322.6 U/kg per month, P  = 0.003), and iron sucrose group received significantly lower iron dose than the Fe chloride group at week 8 ( P  = 0.005).
Conclusion:   Although the differences in ESA dosage, ferritin and iron dosage between two groups were found during the study period while similar results were shown at the end of 24 week study. Thus, iron sucrose and Fe chloride are safe and work equally well for haemodialysis patients.     

A randomized, controlled parallel-group trial on efficacy and safety of iron sucrose (Venofer) vs iron gluconate (Ferrlecit) in haemodialysis patients treated with rHuEpo.

BACKGROUND: The objectives of the present trial were to compare the efficacy and safety of two i.v. iron preparations with respect to haemoglobin levels, iron status and recombinant human erythropoetin (rHuEpo) dosage requirements in stable, rHuEpo-treated haemodialysis patients (maintenance phase of iron treatment) over 6 months. METHODS: A total of 59 patients were randomized and assigned to one of two treatment groups and 55 patients were analysed (iron sucrose n=27; iron gluconate n=28). Iron sucrose was administered in a dose of 250 mg iron diluted in 100 ml normal saline given over 60 min once per month, while 62.5 mg iron as iron gluconate was given once per week in a slow push injection (5 min). RESULTS: --Efficacy parameters: Haemoglobin levels could be maintained from baseline to endpoint in both groups. There were, however, more patients in the iron sucrose group than in the iron gluconate group for whom treatment was discontinued because their haemoglobin values exceeded 12.5 g/dl or ferritin values exceeded 1000 ng/ml (five vs two and three vs one patient, respectively). Transferrin saturation and serum ferritin increased significantly in both groups (+255.7 ng/ml with iron sucrose and +278.5 ng/ml with iron gluconate), while rHuEpo dosage did not change significantly throughout the study. --Safety parameters: There were a total of 174 infusions of iron sucrose and 720 injections of iron gluconate during the trial; all of them were well tolerated. In particular, we did not observe anaphylactoid reactions or any events suggestive of iron toxicity such as hypotension, dizziness, or nausea. CONCLUSIONS: High doses of iron sucrose (Venofer((R)) at a dose of 250 mg/month) was equally effective in maintaining haemoglobin and equally well tolerated as low doses of iron gluconate (Ferrlecit((R)) at a dose of 62.5 mg once per week) in stable, rHuEpo treated haemodialysis patients.     

Iron availability and complex stability of iron hydroxyethyl starch and iron dextran a comparative in vitro study with liver cells and macrophages.

BACKGROUND: Intravenous iron (IVI) therapy is required in patients with end-stage renal disease (ESRD) under chronic haemodialysis (HD). In this in vitro study we investigated the availability and stability of iron hydroxyethyl starch (iron-Hes) compounds in THP-1 cells (macrophage phenotype) and liver cells (HepG2 cells) and compared it with the well-known iron dextran. METHODS: The uptake and release of these iron formulations by THP-1 cells (macrophage phenotype) and HepG2 cells were investigated with atomic absorption spectrometry (AAS). Ferritin was measured by ELISA. HepG2 cells were used to investigate effects of IVI on the intracellular labile iron pool (LIP), which was measured by using the fluorescent calcein assay. The amount of redox-active iron within the iron formulations was assayed using dichlorofluorescein as fluorescent probe. RESULTS: All iron preparations were taken up, stored in ferritin and released again by macrophages and HepG2-cells. This study shows that the availability and stability of iron-HES formulations in vitro are comparable with the well-known iron dextran compounds. CONCLUSIONS: Our results indicate that these new iron formulations have a good stability and availability in vitro and are comparable with the well-known iron dextran complexes.     

An indistinct balance: the safety and efficacy of parenteral iron therapy.

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.     

The comparative efficacy and safety of sugammadex and neostigmine in reversing neuromuscular blockade in adults. A Cochrane systematic review with meta‐analysis and trial sequential analysis

We compared the efficacy and safety of sugammadex and neostigmine in reversing neuromuscular blockade in adults. Our outcomes were: recovery time from second twitch to train‐of‐four ratio > 0.9; recovery time from post‐tetanic count 1–5 to train‐of‐four ratio > 0.9; and risk of composite adverse and serious adverse events. We searched for randomised clinical trials irrespective of publication status and date, blinding status, outcomes reported or language. We included 41 studies with 4206 participants. Time to reversal of neuromuscular blockade from second twitch to a train‐of‐four ratio > 0.9 was 2.0 min with sugammadex 2 mg.kg^?1 and 12.9 min with neostigmine 0.05 mg.kg^?1, with a mean difference (MD) (95%CI)) of 10.2 (8.5–12.0) (I² = 84%, 10 studies, n = 835, Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate quality). Time to reversal of neuromuscular blockade from a post‐tetanic count of 1–5 to a train‐of‐four ratio > 0.9 was 2.9 min with sugammadex 4 mg.kg^?1 and 48.8 min with neostigmine 0.07 mg.kg^?1, with a MD (95%CI) of 45.8 (39.4–52.2) (I² = 0%, 2 studies, n = 114, GRADE: low quality). There were significantly fewer composite adverse events in the sugammadex group compared with neostigmine, with a risk ratio (95%CI) of 0.60 (0.49–0.74) (I² = 40%, 28 studies, n = 2298, number needed to treat (NNT): 8, GRADE: moderate quality). Specifically, the risk of bradycardia (RR (95%CI) 0.16 (0.07–0.34), n = 1218, NNT: 14, GRADE: moderate quality), postoperative nausea and vomiting (RR (95%CI) 0.52 (0.28–0.97), n = 389, NNT: 16, GRADE: low quality) and overall signs of postoperative residual paralysis (RR (95%CI) 0.40 (0.28–0.57), n = 1474, NNT: 13, GRADE: moderate quality) were all reduced. There was no significant difference regarding the risk of serious adverse events (RR 0.54, 95%CI 0.13–2.25, I² = 0%, n = 959, GRADE: low quality). Sugammadex reverses neuromuscular blockade more rapidly than neostigmine and is associated with fewer adverse events.     

Evaluation of the safety and efficiency of the dorsal slit and sleeve methods of male circumcision provided by physicians and clinical officers in Rakai, Uganda

Study Type – Therapy (outcomes research) Level of Evidence 2c What’s known on the subject? and What does the study add? MC reduces heterosexual acquisition of HIV in men for safe and efficient rapid scale‐up; task shifting from physicians to clinical officers is safe and the use of bipolar cautery will reduce operative time, but is associated with higher adverse events.

OBJECTIVE

? To assess the safety and efficiency of the dorsal slit and sleeve male circumcision (MC) procedures performed by physicians and clinical officers (COs).

PATIENTS AND METHODS

? We evaluated the time required for the MC procedure (efficiency) and moderate/severe adverse events (AEs) for MC (safety) by trained physicians and COs using the sleeve and dorsal slit MC methods in a service programme. ? Univariate and multiple regressions with robust variance estimation were used to assess factors associated with operative duration (linear) and AEs (logistic).

RESULTS

? Six physicians and eight COs conducted 1934 and 3218 MCs, respectively; there were 2471 dorsal slit and 2681 sleeve MC procedures. The overall mean operative duration was 33 min for newly trained providers, whichdecreased to ≈20 min after ≈100 MCs. ? The adjusted mean operative duration for dorsal slit MC was significantly shorter than that for the sleeve MC method (Δ? 2.7 min, P < 0.001). ? The operative duration was longer for COs than physicians for the sleeve procedure, but not the dorsal slit procedure; however this difference reduced with increasing numbers of MCs completed. ? The unadjusted AE rates were 0.6% for dorsal slit MC and 1.4% for the sleeve method (P= 0.006) and 1.5% for physicians and 0.68% for COs (P= 0.003); however, there were no significant differences after multivariate adjustment. ? Use of bipolar cautery significantly reduced operative duration (Δ? 4.0 min, P= 0.008), but was associated with higher AE rates (adjusted odds ratio 2.13, 95% confidence interval 1.26–3.61, P= 0.005).

CONCLUSION

? The dorsal slit MC method is faster than sleeve resection, and can be safely performed by non‐physicians; however, use of bipolar cautery may be inadvisable in this setting.     

左胸小切口多支动脉化冠状动脉旁路移植术64例的有效性和安全性分析

目的探讨左胸小切口冠状动脉旁路移植术多支动脉桥策略的安全性及有效性,为该技术推广提供证据。方法回顾性分析2015年12月至2019年11月北京大学第三医院心脏外科64例左胸小切口多支搭桥手术患者的临床资料。男54例、女10例,年龄36~77(61.1±8.7)岁。经第5肋间长5~8 cm左胸前外侧切口进胸,在非体外循环下进行手术,借助胸壁悬吊装置及心脏固定器,完成升主动脉近端吻合,前降支、回旋支及右冠状动脉系统的靶血管远端吻合等操作。移植血管数量2~4(2.3±0.5)支,其中45例患者移植2支,17例移植3支,2例移植4支;手术结合经皮冠状动脉介入治疗(PCI)杂交治疗3例,全动脉化旁路移植62例。术后7 d内复查冠状动脉造影评估旁路血管通畅率,随访记录主要不良心脑血管事件(MACCE)发生情况,通过Kaplan-Meier法计算免于发生MACCE率。结果无患者中转开胸手术,术中未应用主动脉内球囊反搏或体外膜肺氧合。术后切口愈合不良1例,再次手术2例(均为术后胸腔出血)。术后30 d内发生非致死性心肌梗死1例,无死亡。术后早期复查造影旁路血管总体通畅率为96.2%,前降支旁路通畅率为98.2%。随访12~60个月(中位随访时间28个月)。失访率7.8%(5/64)。36个月免于MACCE发生率为84.9%(95%CI 79.5%~90.3%)。结论左胸小切口多支冠状动脉旁路移植术可以实现完全再血管化及全动脉化搭桥,近期及中远期效果良好。     

Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients.

BACKGROUND: Serum ferritin is a frequently used marker of iron status in dialysis patients. Iron administration is to be withheld for ferritin values >800 ng/ml according to K/DOQI guidelines. We hypothesized that such non-iron-related factors as elements of the malnutrition-inflammation complex syndrome (MICS) may increase serum ferritin concentration independently of iron status. METHODS: We studied 82 prevalent maintenance haemodialysis (MHD) patients (including 43 men), aged 55.7 +/- 15.3 years. The inflammatory and nutritional status was evaluated by serum C-reactive protein (CRP), Subjective Global Assessment (SGA) and its newer, fully quantitative versions, i.e. Dialysis Malnutrition Score (DMS) and Malnutrition-Inflammation Score (MIS). RESULTS: All but six patients had been on maintenance doses of intravenous iron dextran (between 100 and 200 mg/month) during the 10 weeks prior to the measurements. Serum ferritin levels were increased across SGA categories: (ANOVA P-value 0.03). Both unadjusted and multivariate adjusted correlation coefficients (r) for serum ferritin and CRP vs pertinent values were statistically significant for DMS and MIS and some other measures of nutritional status and iron indices. After deleting 10 MHD patients with either iron deficiency (ferritin <200 ng/ml) or iron overload (ferritin >2000 ng/ml), in the remaining 72 MHD patients both bivariate and multivariate correlations were much stronger and statistically significant (r = -0.33 and -0.29, respectively, P < 0.01). A multivariate model showed simultaneous, significant correlations between serum ferritin and both markers of inflammation and iron status independent of each other. After dividing the 72 MHD patients into two groups of serum ferritin based on a K/DOQI recommended serum ferritin cut-off of 800 ng/ml, the MIS and logarithm of serum CRP were significantly higher in the higher ferritin group. CONCLUSIONS: Serum ferritin values in the range of 200-2000 ng/ml may be increased due to non-iron-related factors including elements of MICS.     

Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients.

BACKGROUND: Intravenous iron is a recognized therapy of anaemia in chronic haemodialyzed patients, especially in those receiving erythropoietin (Epo), while its role in the anaemia of pre-dialyzed chronic renal failure (CRF) patients is much less clear. This study attempted to evaluate the effects of intravenous iron in anaemic pre-dialyzed patients. METHODS: Sixty anaemic (haemoglobin<11 g/dl) non-diabetic patients with moderate CRF [32 males, 28 females; mean age 52.2+/-12.5 years; mean glomerular filtration rate 36.2+/-5.2 ml/min], without iron deficiency, iron overload or inflammation, without concomitant erythropoietin treatment and without any previous iron therapy were enrolled. Intravenous iron was administered as iron sucrose, 200 mg elemental iron per month for 12 months, with 1 month pre-study survey and 1 month follow-up after the last iron dose. RESULTS: Intravenous iron supplementation was associated with a significant increase in haemoglobin (from 9.7+/-1.1 at the baseline to 11.3+/-2.5 g/dl after 12 months, a mean increase of 1.6 g/dl), a further 36% of patients reaching the target haemoglobin of 10 g/dl. There was a significant increase in serum iron from 73.9+/-17.2 to 101.8+/-12.2 microg/dl, in serum ferritin from 98.0 (24.8-139.0) to 442.5 (86.0-496.0) microg/l and in transferrin saturation from 21.6+/-2.6 to 33.6+/-3.2%. No worsening of renal function, no increase in blood pressure and no other side effects were noted. CONCLUSIONS: Intravenous iron therapy in pre-dialysis patients with no Epo seems often to ameliorate the anaemia, avoiding the necessity of Epo or blood transfusions in one-third of pre-dialyzed non-diabetic patients. Intravenous iron supplementation appears to be an effective and safe treatment for anaemia in pre-dialysis CRF patients.