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.     

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.     

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.     

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.     

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.     

Dehydroascorbic acid and oxidative stress in haemodialysis patients.

BACKGROUND: The amount of dehydroascorbic acid contained within total ascorbic acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as the dehydroascorbic acid fraction, may be a measure of oxidative stress during haemodialysis. In the present study, we determined this fraction in chronic haemodialysis patients. METHODS: Using high performance liquid chromatography, dehydroascorbic acid and total ascorbic acid levels were measured in 80 maintenance haemodialysis patients for a period of > 2 years as well as in 49 controls, to examine a possible association of these compounds with clinical parameters and/or drugs taken by the patients. RESULTS: Dialysis patients who had an increased plasma urate level (P < 0.05) and had been taking allopurinol (P < 0.05) or NSAID (non-steroid anti-inflammatory drugs) (P < 0.01), and dialysis patients who were younger (< or = 55 years), as compared with older dialysis patients (P < 0.01), were found to have a lower dehydroascorbic acid fraction by multivariate analysis. Mean plasma dehydroascorbic acid levels and dehydroascorbic acid fractions were significantly lower in the younger haemodialysis patients (4.8 +/- 0.7 micromol/l and 28.4 +/- 3.9%) than in healthy younger controls (13.3 +/- 1.1 micromol/l and 41.1 +/- 1.8%) (P < 0.0001 and P < 0.01, respectively). Moreover, a correlation was found between plasma dehydroascorbic acid fraction and plasma lipid peroxide (r = 0.66, P < 0.01) in patients who had not been taking allopurinol and/or NSAID. CONCLUSION: We found that dehydroascorbic acid fraction was related to patients' age, plasma urate level and to taking allopurinol or NSAID. Dehydroascorbic acid fraction may be another indirect index of oxidative stress.     

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.     

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.     

Chronic hepatitis ameliorates anaemia in haemodialysis patients

Background: Study for influence of chronic hepatitis (CH) on anaemia in haemodialysis (HD) patients remains inconclusive. We aim to characterize the red cell status between CH and hepatitis‐free groups among the HD population. Methods: We retrospectively analysed 80 chronic HD patients from Taipei Medical University Hospital with monthly sampled biochemical study between December 2004 and December 2005. Data classified according to the hepatitis‐free, chronic hepatitis B and C groups were expressed as mean ± standard deviation. Student's t‐test and anova were used to determine the mean difference for continuous variables. Results: Age, Kt/V, systolic or diastolic blood pressure, body mass index, total cholesterol and triglyceride were not different between CH and hepatitis‐free groups. HD duration (P = 0.0002), aspartate (P < 0.0001), alanine aminotransferase (P < 0.0001), alkaline phosphatase (P = 0.04), haemoglobin (P = 0.0066) and haematocrit (P = 0.002) were significantly more elevated in the CH group demanding less erythropoietin dose than in the hepatitis‐free group. Conclusion: Our study demonstrated that lessoned anaemia was observed in CH, which demanded less erythropoietin dose.     

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.     

Oxidative stress from rapid versus slow intravenous iron replacement in haemodialysis patients

METHODS AND RESULTS: Oxidative stress was examined in 19 erythropoietin-treated haemodialysis patients who were receiving 100 mg of iron sucrose every 2 weeks by two intravenous methods, rapid injection and slow infusion. There were no significant differences in incidence of iron oversaturation state between the two methods. Regarding oxidative stress markers, the values of plasma and red blood cell thiobarbituric acid reactive substances (TBARS) expressed in terms of malonyldialdehyde (MDA) equivalents following the two methods did not increase, and the values of area under the curve (AUC) of both markers were not different between both regimens. Also, there were no significant differences in the values of plasma and AUC of anti-oxidant markers including total anti-oxidant status, reduced thiols, and vitamin E among both periods treated with two intravenous iron methods. CONCLUSION: As such, both intravenous iron methods could be safely used without enhancing oxidative stress in haemodialysis patients. The rapid injection method would be the preferred method of intravenous iron administration because it is more convenient while still retaining the safety profile.     

Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients

Recombinant human erythropoietin (rHuEpo) was used to treatthe anaemia of four haemodialysed patients (3 males, 1 female)with advanced multiple myeloma; the type of serum M componentwas IgG kappa in all cases. During the 6-month period precedingrHuEpo therapy the patients received multiple blood transfusions(range 4–22 units of packed red cells per patient). Afterthe first month of treatment haematocrit increased from 23±3(SD) to 32±4% and during the last 3 months the maintenancedose of rHuEpo was 143±37 U/kg per week to achieve amean haematocrit of 35±1%. After introduction of rHuEpo,blood transfusions were no longer required and the patientsreported an improvement in wellbeing. No apparent worseningof multiple myeloma has been observed over the treatment periodranging from 5 to 34 months (cumulative duration of treatment55 months). Anti-hypertensive therapy was started in one caseand increased in two patients. We conclude that rHuEpo appearsto be effective and safe in treating anaemia associated withmultiple myeloma in patients requiring haemodialysis.     

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.     

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.     

A prospective multicentre study of the role of anaemia as a risk factor in haemodialysis patients: the MAR Study.

BACKGROUND: Retrospective studies have shown hospitalization and mortality rates during haemodialysis (HD) to be associated with anaemia. METHODS: The prospective, multicentre Morbidity-and-mortality Anaemia Renal (MAR) study was designed to establish the burden of anaemia by controlling for other risk factors. Charlson index was used for comorbid adjustment. Finally, 1428 patients from 119 centres (60% men, aged 64.4 years, time on HD 15.3 months, Charlson comorbidity index 6.5 +/- 2.3) completed follow-up. They had hypertension (75.8%), diabetes mellitus (25.9%), heart failure (13.9%) and coronary disease (16.7%). Of the total patients, 94.8% were receiving erythropoietin (111.6 +/- 70.6 U/kg/week) and 76.7% i.v. iron, and haemoglobin (Hb) at inclusion was 11.7 +/- 1.5 g/dl. RESULTS: Hospitalization rate was 1.1 admissions/patient/year. Yearly mortality was 12% [35% cardiovascular (CV)]. The relative risk and confidence interval (CI) for hospitalization and death were 0.86 (0.81-0.91) and 0.82 (0.73-0.91), respectively, per 1 g/dl increase in initial Hb after adjustment for comorbidity, vintage, aetiology, access type, albumin and Kt/V. The probability of remaining free from hospitalization (CI) was 0.34 (0.27-0.41) for initial Hb <10 g/dl, 0.47 (0.41-0.53) for Hb 10-11 g/dl, 0.54 (0.49-0.59) for Hb 11-12 g/dl, and 0.63 (0.59-0.67) for Hb >12 g/dl. Same analysis for patient survival was 0.77 (0.71-0.83) for Hb <10 g/dl vs 0.82 (0.77-0.87) for Hb 10-11 vs 0.89 (0.86-0.92) for Hb 11-12 vs 0.92 (0.90-0.94) for Hb > 12 g/dl, P < 0.001. The Cox regression model for hospitalization-free survival included the risk factors initial Hb (relative risk 0.86 per 1 g/dl increase, P < 0.001) Charlson, albumin and prior CV event. CONCLUSION: Hb level predicted 1-year-survival and hospitalization. This effect persisted after adjustment for comorbidity and other prognostic factors.     

Haemoglobin response to subcutaneous versus intravenous epoetin alfa administration in iron-replete haemodialysis patients

BACKGROUND: Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (s.c.) to intravenous (i.v.) route of administration. Many of the reported trials, however, involved patients who did not have adequate serum iron levels. It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration. METHODS: Haemodialysis patients who were iron replete (ferritin 300-800 microg/L, transferrin saturation (TSAT) 25-50%) participated in a prospective, randomized cross-over trial receiving epoetin for 3 months either by s.c. or i.v. injection followed by a further 3 months of epoetin via the other route. The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose. The secondary aim was to assess whether the frequency of dosing (once, twice or thrice weekly) influenced the Hb concentration response. RESULTS: Eighty-one patients (mean age 62 years, 60% male) entered the study and 15 withdrew prior to study completion. Forty-three patients began s.c. epoetin alfa administration (group A) and 38 on i.v. (group B). Median ferritin and TSAT at entry for groups A and B were 409 and 394 microg/L (NS) and 31 and 32% (NS), respectively, which remained within the target range during the study. Median epoetin doses for groups A and B were similar (90 vs 93 IU/kg per week, NS). After 3 months, the mean Hb concentration rose for group A (SC; 118.7-121.9 g/L (P = 0.03)) but it fell for group B (i.v.; 119.1-116.0 g/L (P = 0.019)). Following the change in route of administration, the Hb concentration for group A (i.v.) fell by 5.1% over 3 months (121.9-115.4, P < 0.001) and rose by 2.8% for group B (s.c.) over 3 months (116.0-119.7, P = 0.001). Similar significant changes in the Hb concentration were seen at different dosing frequencies. CONCLUSION: Subcutaneous administration of epoetin produces a significant, although slight clinical change in Hb concentration compared with i.v. administration in stable, iron replete, haemodialysis patients. A similar effect appears to prevail regardless of the frequency of injections given.     

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.