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.     

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.     

Regular low-dose intravenous iron therapy improves response to erythropoietin in haemodialysis patients

BACKGROUND.: Erythropoietin (Epo) is an effective but expensive treatmentfor anaemia in patients with chronic renal failure. Hyporesponsivenessto Epo, particularly in haemodialysis patients, is most commonlydue to a functional iron deficiency, which is difficult to monitorreliably. METHODS.: Forty-six stable haemodialysis patients, receiving Epo therapy,were commenced on regular low-dose intravenous iron (sodiumferric gluconate complex) at a dose of 62.5 mg/5 ml given asa slow injection post-dialysis twice weekly, weekly, or fort-nightly,according to their serum ferritin levels. Haemoglobin, serumferritin, Epo dose, and iron dose were measured at 6-weeklyintervals over a 6-month period. RESULTS: At the beginning of the study, 12 patients in the group hadferritin levels of less than 100 µg/l, and were thus consideredto potentially have an absolute iron deficiency. The study groupwas therefore split into two subgroups for the purpose of analysis,i.e. the 12 patients with ferritin levels of less than 100 µg/lat the start of the study or ‘low ferritin group’,and the remaining 34 patients with ferritin levels of greaterthan 100 µg/l at the start of the study or ‘normalferritin group’. In the low ferritin group (n=12), intravenous iron therapy increasedserum ferritin levels, and produced a significant rise in haemoglobin,and a significant reduction in Epo dose. (Ferritin pre-iron,median (range) 68 (20–96)µg/l; post-iron, 210.5(91–447)µg/l, P<0.003, Wilcoxon. Haemoglobinpre-iron, 10.05 (8.2–11.9)g/dl; post-iron, 11.0 (9.9–11.9)g/dl,P<0.03. Epo dose pre-iron, 9000 (4000–30000) i.u./week;post-iron, 6000 (2000–10000)i.u./week, P<0.05.) Similar results were obtained in the normal ferritin group (n=34)following intravenous iron therapy, with significant increasesin serum ferntin levels and haemoglobin concentrations, anda significant reduction in Epo dose. (Ferritin pre-iron, 176(103–519) µg/l; post-iron, 304.5 (121–792)µg/l,P<0.0001. Haemoglobin pre-iron, 9.85 (6.5–12.8)g/dl;post-iron: 11.25 (9.9–13.3)g/dl, P<0.0001. Epo dosepre-iron, 6000 (2000–15 000)i.u./week; post-iron, 4000(0–15000)i.u./week, P<0.005.) CONCLUSION.: Regular intravenous iron supplementation in haemodialysis patientsimproves the response to Epo therapy.     

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.     

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.     

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.     

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.     

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.     

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.     

Determinants of circulating soluble transferrin receptor level in chronic haemodialysis patients.

BACKGROUND: The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTfR) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment. METHODS: In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTfR. HD patients received constant rHuEpo doses and basal sEpo was measured > or = 86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log(10)sTfR) as a dependent variable in the forward stepwise multiple regression model. RESULTS: HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTfR, sEpo, and reticulocyte index. Univariate analyses showed that the sTfR level strongly correlated with sEpo (r=0.60, P<0.001) and % HRC (r=0.60, P<0.001), and significantly with serum ferritin (r=-0.29, P<0.01), TS (r=-0.27, P<0.05), and dose of rHuEpo administered (r=0.27, P<0.05) in HD patients. sTfR also had a positive correlation with haematocrit (r=0.26, P<0.05), red blood cell (RBC) count (r=0.23, P<0.05), and reticulocyte count (r=0.24, P<0.05), but not with CRP (r=0.16, P>0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTfR level. Overall, the model explained 58.8% of the variability in sTfR (R(2)=0.588, P<0.001). CONCLUSIONS: Circulating sTfR is a good index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTfR levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.     

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.     

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.     

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.     

Effect of repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels.

BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.     

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.     

Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV-infected haemodialysis patients.

BACKGROUND: Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis. METHODS: An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point. RESULTS: Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa. CONCLUSIONS: Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.