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.     

Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients.

BACKGROUND: Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. METHODS: We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. RESULTS: Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 +/- 159 at baseline to 490 +/- 275 microg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 +/- 1.1 at baseline and 12.1 +/- 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 microg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. CONCLUSIONS: A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patients.     

Efficacy of low‐dose i.v. iron therapy in haemodialysis patients

Aim: i.v. iron therapy is more effective in maintaining adequate iron status in haemodialysis (HD) patients than oral iron therapy (OIT). However, data on lower doses of i.v. iron therapy are insufficient. Methods: A non‐randomized, open‐label study was performed to compare the efficacy of low‐dose (≤50 mg/week of iron sucrose) i.v. iron therapy (LD‐IVIT) with OIT in HD patients with 100–800 µg/L serum ferritin levels over 4 months. Results: Eighty‐nine patients in the LD‐IVIT group (40 men, 49 women; aged 61 ± 13 years) and 30 patients in the oral iron therapy group (17 men, 13 women; aged 59 ± 7 years) were evaluated. After 4 months of each treatment, serum ferritin levels increased from 398 ± 137 to 529 ± 234 µg/L in the LD‐IVIT group (P < 0.01) but decreased from 351 ± 190 to 294 ± 175 µg/L in the OIT group (P < 0.01). In the LD‐IVIT group, transferrin saturation (from 28% ± 11% to 30% ± 14%, P = 0.49), weekly doses of recombinant human erythropoietin (from 5822 ± 2354 to 5636 ± 2306 IU/week, P = 0.48) and haemoglobin (from 101 ± 9 to 103 ± 9 g/L, P = 0.15) levels remained stable. Conclusion: LD‐IVIT may be one of the regimens that may be considered for maintaining iron status in HD patients. However, efficacy of LD‐IVIT should be verified by further randomized study.     

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.     

'Oversaturation' of transferrin after intravenous ferric gluconate (FerrlecitR) in haemodialysis patients

BACKGROUND: Chronic haemodialysis causes blood loss and iron-deficiency.This can be corrected with intravenous preparations, e.g. sodiumferric-gluconate (FeGl). In two patients complaints of hypotensionand malaise during FeGl infusion coincided with high levelsof serum iron and a calculated transferrin iron saturation above100%. Iron toxicity could be the cause of these complaints.Free iron is known to aggravate the toxicity of free radicalsand other reactive oxygen products that are constantly formedin the body. We compared four rates of FeGl infusion with regardto iron parameters. METHODS: 20 dialysis patients received a total of 36 infusions of FeGl.A rapid infusion of 125 mg (Protocol A (n=10)) or 62.5 mg (ProtocolB (n=7)) of FeGl was given during the last 30 min of dialysis.A slow infusion of 125 mg (Protocol C (n=9)) or 62.5 mg (ProtocolD (n=10)) was given during 4 or 4.5 h of dialysis. Blood wastaken at regular intervals before, during, and after dialysisfor determination of serum iron, transferrin, ferritin, haematocrit,total protein, albumin, and lactate dehydrogenase (LDH). Transferrinsaturation was calculated from transferrin and serum iron. RESULTS: With rapid infusion A (125mg) the highest levels of serum iron(median 120 (range 40–159) micromol/l) and transferrinsaturation (207 (84–331)%) were seen at the end of theinfusion. These were significantly higher than the peak levelswith B, C, and D (P0.03). With rapid infusion B (62.5 mg), peaklevels were intermediately high (serum iron 61 (50–96)µmol/l; transferrin saturation 118 (91–174)%). Withslow infusion C (125 mg) similar peak levels were seen (serumiron 83 (43–106) µmol/l; transferrin saturation141 (88–172)%). With slow infusion D (62.5 mg), the lowestpeak levels were seen (serum iron 38 (31–55) µmol/l;transferrin saturation 78 (43–92)%). These levels weresignificantly lower than those with A, B and C (p0.002). Onlywith D all patients showed a transferrin saturation lower than100%. Ferritin was increased before the next dialysis in allpatients. LDH was not significantly elevated during any infusion. CONCLUSIONS: The commonly used rapid infusion rate (A) of FeGl causes ‘oversaturation’of transferrin. This is compatible with iron toxicity due tofree iron which may explain our patients' complaints. Free ironcannot be measured directly. LDH as a crude measure of celldamage was not elevated. Better measurements to prove free irontoxicity, like lipid peroxides, are not yet readily available.Infusion during a longer period at a lower dose (D) is effectiveand eliminates ‘oversaturation’ of transferrin andprobably the danger of iron toxicity.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

SUMMARY: We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60 ± 0.64 G/ dL vs 10.5 G/dL ± 1.14 P <0.01). the final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400 ± 1356 U/week vs 4600 ± 1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL ± 388 vs 367 ng/mL ± 238 P =NS). the same was also observed with transferrin saturation (44.6%± 19.8 in Group 1 vs. 29%± 11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

Randomized trial to compare the dosage of darbepoetin alfa by administration route in haemodialysis patients

Aim:   The doses of darbepoetin alfa required to maintain target haemoglobin levels after s.c. or i.v. administration when recombinant human erythropoietin (rHuEpo) treatment was replaced by darbepoetin alfa treatment in haemodialysis (HD) patients were compared.
Methods:   In this prospective, randomized, open-label study, 65 HD patients who were receiving stable SC doses of rHuEpo were switched to an equivalent dose of darbepoetin alfa at a reduced frequency by s.c. or i.v. administration. Patients were randomly assigned to the s.c. group ( n  = 32) or the i.v. group ( n  = 33). Darbepoetin alfa doses were titrated to maintain target haemoglobin levels of 8.0–11.0 g/dL for up to 24 weeks. A period of 20 weeks was used for dose titration and haemoglobin stabilization. This was followed by a 4 week evaluation period.
Results:   The mean haemoglobin concentration during the evaluation period was similar in the s.c. and i.v. groups. The mean dose and mean weight-standardized dose of darbepoetin alfa during the evaluation period tended to be lower in the s.c. group than the i.v. group, although these differences were not statistically significant. The mean weekly darbepoetin alfa dose requirements during the evaluation period significantly decreased in both groups compared to the dose requirements at randomization.
Conclusion:   There is a possibility that s.c. administration of darbepoetin alfa is more efficacious than i.v. administration, but a definite benefit cannot be demonstrated with the current sample size. A bigger sample size is needed to confirm the result.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60±0.64 G/dL vs 10.5 G/dL±1.14 P <0.01). The final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400±1356 U/week vs 4600±1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL±388 vs 367 ng/mL±238 P =NS). The same was also observed with transferrin saturation (44.6%±19.8 in Group 1 vs. 29%±11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

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.     

Crossover comparison of intravenous and subcutaneous erythropoietin in haemodialysis patients.

To examine the suggestion that s.c. administration of recombinant human erythropoietin (rHuEpo) may be more effective than i.v. administration, we changed the route of administration in 11 patients, previously established on a stable dose of rHuEpo given twice or thrice weekly, from i.v. to s.c. administration without altering the dose. All patients were iron replete (serum ferritin greater than 100 micrograms/l). In one patient the haemoglobin concentration declined at the time of conversion due to poor compliance, and another patient died shortly after conversion. In the remainder there was a significant increase in haemoglobin concentration from 9.30 (SD 0.78) at the time of conversion to 9.84 (0.59) at 1 month, 10.35 (1.22) at 2 months, and 10.39 (1.42) at 3 months. The increase in haemoglobin concentration was greater than 1 g/dl at 3 months in only five of the patients. Serum ferritin prior to conversion was similar in 'responders' and 'non-responders', but all responders had a transferrin saturation of greater than 16%, whereas three of four non-responders had transferrin saturation of less than or equal to 16%. Subcutaneous administration of rHuEpo is more effective, dose for dose, than i.v. administration, but poor iron mobilization may limit the response.     

A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin.

BACKGROUND: Correction of anaemia as a result of renal failure improves cardiovascular function and also provides significant cognitive and emotional benefits. The most appropriate route for iron supplementation has not been determined for patients with chronic renal failure who are not yet on dialysis. METHODS: Forty-five anaemic patients with progressive renal insufficiency (PRI) were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo) was simultaneously commenced and the dose adjusted according to a pre-established protocol. RESULTS: There were no significant differences in baseline patient characteristics between the two groups. The average follow-up was 5.2 months. Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin response and changes in red cell hypochromasia were similar in the two groups, but serum ferritin was significantly higher in the intravenous group. The starting dose of rHuEpo could be temporarily discontinued in 43% of patients on oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased after 3 months in 9% of patients on oral iron and 19% of patients receiving iron sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week respectively in the oral and intravenous groups (NS). Although gastro-intestinal symptoms were more commonly reported in patients taking oral iron, these were mild according to scores on visual analogue scales. Dietary protein and energy intake were not significantly different in the two groups at 0, 3 and 6 months. CONCLUSIONS: In pre-dialysis patients, the efficacy of monthly 300 mg iron sucrose given intravenously is not superior with regard to haemoglobin response and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate or equivalent. Where intravenous iron is preferred, lower doses may help to reduce the incidence of allergic or "free iron" reactions, especially in patients with low body mass.     

Efficacy and safety of oral versus intravenous ascorbic acid for anaemia in haemodialysis patients

BACKGROUND: Intravenous (i.v.) ascorbic acid (AA) improves anaemia in iron-overloaded, erythropoietin (rEPO) hyporesponsive haemodialysis patients. While oral AA is readily attainable, the efficacy and safety of oral versus i.v. AA has not been examined. METHODS: We conducted an open-label randomised parallel study on the effects of 8 weeks of 250 mg oral AA (n=10) compared with 250 mg i.v. AA (n=11) 3x/week on haemoglobin (Hb), ferritin and rEPO dose in 21 iron-overloaded haemodialysis patients. We also examined the effect of 3 months of 500 mg oral AA 3x/week (n=70) compared with no treatment (n=83) on Hb, ferritin and rEPO dose in 153 haemodialysis patients. RESULTS: Patients had severe AA deficiency (mean 2.2+/-SE 0.4 mg/L; normal range, 4.0-14.0). Following treatment, the plasma AA level increased (P<0.001), but was not significantly different between the groups. There was no change in Hb, iron availability and rEPO dose with oral or i.v. AA. There was a significant increase in serum oxalate but no significant changes in left ventricular function or renal calculi formation. In the second study, oral AA had no effect on Hb, rEPO dose and ferritin in the whole group and a subgroup of 30 with anaemia. CONCLUSION: Haemoglobin and iron availability did not improve following oral or i.v. AA in this select small group of iron-overloaded haemodialysis patients or in a larger population of haemodialysis patients given oral AA at a higher dose and for a longer duration. AA supplementation may still be warranted in view of severe AA deficiency in haemodialysis patients.     

Effect of erythropoietin on lipid profile in haemodialysis patients

Summary: Effect of recombinant human erythropoietin (rHuEPO) was determined on lipid levels (i.e. total cholesterol, triglycerides, high density lipoproteins [HDL], low density lipoproteins [LDL]) of 17 anaemic patients on maintenance haemodialysis. Estimations were done before initiating rHuEPO therapy and repeated 6 months later. There was an increase in haemoglobin (7.6 ± 1.09 to 10.9 ± 1.62 gm/dL, P < 0.001), and a significant decrease in total cholesterol (217 ± 22 to 196 ± 18 mg/dL, P < 0.001) and triglyceride levels (200 ± 20 to 186 ± 15 mg/dL, P < 0.001). There was no significant effect on HDL and LDL levels.     

Early prediction of response to intravenous iron supplementation by reticulocyte haemoglobin content and high-fluorescence reticulocyte count in haemodialysis patients.

BACKGROUND: Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo. METHODS: Sixty-five HD patients with a serum ferritin level of <500 microg/l and on rHuEpo therapy for >6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of >3% and/or a reduction in rHuEpo dose of >30% over the baseline values at the end of the study. RESULTS: Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P<0.001). This paralleled a statistically significant rise in CHr and HFR (P<0.001). Univariate analyses showed that ferritin (P<0.010) and CHr (P<0.001) at baseline, changes in CHr (DeltaCHr(2W), P<0.001) and HFR (DeltaHFR(2W), P<0.010) at 2 weeks, as well as changes in CHr (DeltaCHr(4W), P<0.001) and HFR (DeltaHFR(4W), P<0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that DeltaCHr(4W) in conjunction with DeltaHFR(4W) exhibited an r(2) value of 0.531 (P<0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that DeltaCHr(4W) at a cut-off value of >1.2 pg and DeltaHFR(4W) of >500/microl were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response to IVFE therapy, with a sensitivity of 96% and a specificity of 100%. CONCLUSIONS: Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect iron-deficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.     

Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis

Aim: Haemodialysis induces endothelial dysfunction by oxidation and inflammation. Intravenous iron administration during haemodialysis could worsen endothelial dysfunction. The aim of this study was to ascertain if iron produces endothelial dysfunction and the possible neutralizing effect of N‐acetylcysteine when infused before iron. The oxidative and inflammatory effects of iron during haemodialysis were also assessed. Methods: Forty patients undergoing haemodialysis were studied in a randomized and cross‐over design with and without N‐acetylcysteine infused before iron sucrose (50 or 100 mg). Plasma Von Willebrand factor (vWF), soluble intercellular adhesion molecule‐1 (sICAM‐1) levels, malondialdehyde, total antioxidant capacity, CD11b/CD18 expression in monocytes, interleukin (IL)‐8 in monocytes and plasma IL‐8 were studied at baseline and during haemodialysis. Results: Haemodialysis produced significant (P < 0.001) increase in plasma vWF, sICAM‐1, malondialdehyde, IL‐8 and CD11b/CD18 expression in monocytes, as well as decrease in total antioxidant capacity. Iron induced significant increase in plasma malondialdehyde and IL‐8 in monocytes, but had no effect on total antioxidant capacity, CD11b/CD18 expression, plasma IL‐8, vWF and sICAM‐1. The addition of N‐acetylcysteine to 50 mg of iron produced a significant (P = 0.040) decrease in malondialdehyde. Conclusion: Standard (100 mg) and low (50 mg) doses of iron during haemodialysis had no effects on endothelium. Iron only had minor effects on inflammation and produced an increase in oxidative stress, which was neutralized by N‐acetylcysteine at low iron dose. Haemodialysis caused a significant increase in oxidative stress, inflammation and endothelial dysfunction markers.     

Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin

The efficacy of recombinant human erythropoietin (rHuEpo) forthe treatment of renal anaemia is well established. To assessthe effect of rHuEpo treatment on physical performance we evaluatedphysical working capacity, oxygen uptake and red cell 2,3diphosphoglycerate(DPG) values at rest and during and after exercise on a bicyclespiroergometer in eight chronically haemodialysed patients.Follow-up examination was carried out after a mean of 14 weeks(range 9–19 weeks), when mean haemoglobin had increasedfrom 7.8 to a stable value of 13.0 g/dl in response to rHuEpotreatment (P<0.001). Physical working capacity and oxygenuptake at the anaerobic threshold (4 rnrnol/l blood lactateconcentration) increased from 68±12 to 80±16 wattsand 0.95±0.14 to 1.10±0.20 l/min, respectively(P<0.01). DPG, which determines oxygen affinity to haemoglobinin red cells, increased by 13% from 13.7±1.5 to 15.5±2.2pmol/g Hb (P<0.05 ). With maximal exercise mean DPG valuessignificantly decreased to a much lower level without rHuEpotreatment than after correction of anaemia. Therefore rHuEpotreatment results both in better oxygen transport capacity andreduced intraerythrocytic oxygen affinity, which is followedby improved oxygen delivery to tissues per unit of haemoglobin.These effects may explain the improvement of exercise capacityobserved in dialysis patients after rHuEpo treatment.     

Safety of intravenous injection of iron saccharate in haemodialysis patients

BACKGROUND.: The most frequent i.v. iron preparations used for haemodialysispatients are iron dextran, iron gluconate and iron saccharate.Possible side effects include anaphylactic reactions due topreformed antibodies to dextran or vascular reactions due tounbound iron during treatment with iron gluconate or iron saccharate. METHODS.: Four dosage regimens of i.v. iron saccharate therapy were studied:10, 20, 40 and 100 mg, which were given over a time period of1 min after the end of the dialysis session. Iron metabolismparameters (serum iron concentration, transferrin saturationand serum ferritin levels) were measured at 0, 1, 5, 15 and30 min after application and immediately prior to the next dialysissession. All 18 regular haemodialysis patients studied receivedrecombinant human erythro-poietin (rHuEpo). RESULTS.: Serum iron levels and transferrin saturation increased significantlyfollowing i.v. injection of all doses of iron saccharate. Iron‘oversaturation’ of transferrin iron binding didnot occur in patients with transferrin levels >180 mg/dl.However, in patients with transferrin levels <180 mg/dl theinjection of 100 mg iron saccharate resulted in a transferrinsaturation of 102.6±39.5% (two patients with transferrinlevels of 87 and 92 mg/dl had transferrin saturations of 119.8and 149.7%, two patients with transferrin levels of 148 and171 mg/dl had transferrin saturations of 77.9 and 63.1%, respectively).Serum ferritin levels remained unchanged during the post-injectionperiod and increased by the next dialysis session followinginjection of 100 mg iron saccharate by 165%. CONCLUSIONS.: It is concluded that intravenous iron saccharate injection (10–100mgeven within 1 min) does not result in ‘oversaturation’of transferrin iron binding if serum transferrin levels are>180mg/dl (high-risk patients: transferrin <100 mg/dl). Thismay explain, at least in part, the minimal side effects observedduring the i.v. application of iron saccharate. Low-dose i.v.iron saccharate (10–40 mg) is recommended for iron supplementationof haemodialysis patients. If injection of 100 mg is necessary,serum transferrin level should exceed 180 mg/dl. There is, however,no need for fast i.v. injection during routine iron supplementation.     

Long-term effects on quality of life in haemodialysis patients of correction of anaemia with erythropoietin

Quality of life assessments were performed in 24 haemodialysispatients (10 males, 14 females, age 45 ±15 years) undergoingrHuEpo treatment. The results in the rHuEpo-treated patientswere compared with those in eight haemodialysis patients noton rHuEpo and with the results of a nationwide study of dialysispatients in Sweden (carried out before rHuEpo was registered).Survey questionnaires (112 items, divided into three dimensions,i.e. physical, social, and emotional wellbeing) were completedbefore treatment (Hb 73± 1.1 g/1), when the target Hbvalue of 10 g/dl was reached (1–7 months) and in 14 patients1 year after correction of the anaemia. Before treatment, therHuEpo group had significantly more complaints about poor appetite,fatigue, and irritability than the controls. After the anaemiawas corrected, the rHuEpo group had significantly improved physicaland emotional wellbeing. The most significant changes occurredin satisfaction with health, physical activities of daily life,and fatigue. Alterations in emotional symptoms, such as depressionand apathy, were less pronounced. Only minor changes were observedin their social wellbeing. One year after correction of theanaemia, the improvements in physical and emotional wellbeingwere still present in the rHuEpo-treated patients. A positiveeffect was also noted on hospitalization rate. Scores for thesubdimensions of satisfaction with health, sexual adjustment,physical symptoms, and emotional wellbeing improved in the rHuEpo-treatedgroup and reached a level that was the same, or even higher,than the scores in the dialysis patients in the nationwide study.In conclusion, the quality of life improved during rHuEpo treatment.The greatest changes were seen in satisfaction with health,physical activity, and emotional wellbeing. The positive effectsobserved after the correction of anaemia persisted after morethan a year on rHuEpo treatment.