Aluminium interference in the treatment of haemodialysis patients with recombinant human erythropoietin

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed 1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided into two groups. Group A comprised five patients with a greater mean aluminium (204 +/- 28 micrograms/l) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14-39 g) of DFO over 6 months. Group B (aluminium values 112 +/- 36 micrograms/l) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups. After DFO treatment a second DFO load test was performed. The mean predialysis aluminium value was significantly reduced in group A (204 +/- 28 vs 111 +/- 72 micrograms/l; P less than 0.05), while remaining unchanged in group B (112 +/- 36 vs 140 +/- 39 micrograms/l; P = ns). In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin values decreased with time, but reduced significantly only in group A (298 +/- 105 vs 110 +/- 61 mu/kg per week; delta -63%; P less than 0.01). Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO can allow a considerable sparing of rHuEpo.     

The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.     

Plasma endothelin in haemodialysis patients treated with recombinant human erythropoietin

Predialysis plasma endothelin (ET) values were followed duringthe first 8 weeks of rHuEpo treatment in 12 patients on routinehaemodialysis. Mean plasma ET was significantly increased inuraemic patients before rHuEpo (27.911.4 pmol/1), as comparedto 40 healthy controls (16.55.7 pmol/1) (p<0.0001). UnderrHuEpo treatment, predialysis values remained unchanged althoughdiastolic blood pressure increased after 2 and 6 weeks. We foundno correlation between ET and haemoglobin or blood pressurebefore or under rHuEpo treatment. These results confirmed thehigh levels of plasma ET in haemodialysis patients, but no increasewas observed during rHuEpo treatment.     

Lipid profile in haemodialysis patients treated with recombinant human erythropoietin

Background: The long-term effect of recombinant human erythropoietin (rhEPO) on the blood-lipid profile has not been well documented. The aim of this study was to evaluate whether rhEPO therapy affects the lipid pattern. Methods: A group of 102 maintenance haemodialysis patients were treated for 2 years with rhEPO given intravenously at the end of the dialysis session. Attempts were made to keep the haemoglobin (Hb) at 10-11 g/dl and/or the haematocrit (Hct) at 30-35%. Twenty maintenance haemodialysis patients not treated with rhEPO were examined as controls. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteins A1 and B, and lipoprotein (a) [Lp (a)] were assessed at baseline (without rhEPO), and 1 and 2 years after the beginning of treatment. Hb, Hct and ferritin were measured monthly, and Kt/v was evaluated monthly and kept above 1.1. Results: During follow-up, in both groups, there was a significant increase in Apo A1 and no significant changes in the other lipid parameters. In the treated group, Hb and Hct increased significantly after the fourth month of treatment. Conclusions: Erythropoietin therapy does not affect significantly the levels of total cholesterol, LDL- and HDL-cholesterol, triglycerides, Apo B and Lp (a) in maintenance hemodialysis patients.     

Exercise in hemodialysis patients after treatment with recombinant human erythropoietin

To assess the effect of substantial increases in blood hemoglobin (Hb) caused by treatment with recombinant human erythropoietin (rhEPO) on exercise capacity in maintenance hemodialysis patients, we evaluated 10 patients (7 men and 3 women) at a mean age of 44.3 +/- 8.4 years on maintenance hemodialysis for a mean of 29.7 +/- 30.2 months by treadmill exercise to exhaustion. The patients were tested before administration of rhEPO and after a minimum 1 g/dl rise in Hb. With a change in Hb from 7.1 +/- 1.4 to 9.8 +/- 2.1 g/dl, peak oxygen consumption (VO2 peak) with exercise increased 50.3 +/- 9% (T1 = 15.1 +/- 5.3, T2 = 22.7 +/- 4.6 ml O2/kg/min, p less than 0.05). Respiratory exchange ratio (RER) at a given submaximal exercise level (3 mph, 6% of elevation) decreased significantly (T1 = 1.13 +/- 0.24, T2 = 0.92 +/- 0.08, p less than 0.05). The rhEPO-mediated increase in Hb was associated with an increased VO2 peak--an improvement of the peak exercise capacity and a reduced submaximal RER--reflecting a reduction in anaerobic metabolism at activities of daily living.     

Blood 8-hydroxy-2'-deoxyguanosine is associated with erythropoietin resistance in haemodialysis patients.

BACKGROUND: 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidized DNA, is increased in haemodialysis (HD) patients, but the clinical relevance of enhanced 8-OHdG production in these patients remains unknown. METHODS: We cross-sectionally measured serum 8-OHdG in 73 patients on maintenance HD (age 68+/-2 years, time on HD 85+/-11 months, male/female=42/31), and examined the relationship between blood 8-OHdG and the severity of renal anaemia and the weekly dosage of recombinant human erythropoietin (rHuEPO). RESULTS: There was a significant increase in serum 8-OHdG in HD patients compared with normal subjects. Serum 8-OHdG was positively correlated with the patients' age (r=0.231, P<0.05) but not with the duration of HD. Serum 8-OHdG was significantly higher in diabetic subjects than in non-diabetic subjects (P<0.05). Serum 8-OHdG had a significant inverse correlation with haemoglobin (Hb) (r=-0.526, P<0.01) but a positive correlation with the rHuEPO dose (r=0.443, P<0.01) and the ratio of the weekly rHuEPO dose divided by Hb (r=0.487, P<0.01). Serum 8-OHdG was not correlated with inflammatory and nutritional parameters. CONCLUSIONS: These findings suggest that the elevation of circulating 8-OHdG may be associated, at least in part, with rHuEPO resistance in HD patients.     

A study of recombinant human erythropoietin in the treatment of anaemia of chronic renal failure in children on haemodialysis

This was an open-label multicentre study of recombinant human erythropoietin (r-HuEPO) in 116 children aged 6 months to 20 years with anaemia of chronic renal failure undergoing haemodialysis. Haemoglobin concentration at entry ranged from 3.4 to 9.5 g/dl. r-HuEPO was given intravenously two or three times per week, the starting dose being 75 U/kg per week. This was subsequently titrated in steps of 75 U/kg per week with the goal of increasing haemoglobin concentration at the rate of 1 g/dl per 4 weeks into the range 9.6–11.2 g/dl (6–7 mmol/l), with treatment then continued for up to 1 year with the aim of maintaining the haemoglobin concentration within the target range. Of the 115 children in whom efficacy could be evaluated, 93 (81%) achieved the target haemoglobin and a further 6 had a rise in haemoglobin concentration of at least 2 g/dl. At 52 weeks, the median maintenance dose for children<30 kg was 225 U/kg per week, compared with 107 U/kg per week for children 30 kg. Analysis suggested that 150 U/kg per week would have been a more appropriate starting dose. The mean transfusion requirement fell from 8.9 to 0.7 units/patient per year. Of the 22 patients who failed to reach the target, 15 went on to transplantation and left the study prematurely. Sub-group analysis showed that similar doses lead to similar rates of rise in haemoglobin regardless of the severity of the original anaemia. Assessment of quality of life suggested that this may have improved with r-HuEPO. Twenty-four children needed initiation or increase of anti-hypertensive medication, suggesting that successful r-HuEPO therapy was associated with a tendency towards increased blood pressure. However, there were no significant mean changes in blood pressure, suggesting that the problem was successfully addressed by the changes in treatment. No child developed anti-r-HuEPO antibodies. The overall safety profile was excellent and no new r-HuEPO toxicities were identified in children.     

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.     

Effect of treatment of anaemia with erythropoietin on neuromuscular function in patients on long term haemodialysis.

To study the effect of treatment of anaemia with recombinant human erythropoietin (r-HUEPO) on neuromuscular function in patients undergoing haemodialysis for chronic renal failure, six patients were given r-HUEPO in an initial dose of 50 u/kg three times a week and their haemoglobin concentration was measured. The dose was increased by 25 u/kg every four weeks if the response was not satisfactory. In five patients anaemia had been corrected within 12 weeks of initiation of treatment. Neuromuscular function was evaluated before treatment, half way through, and after correction of anaemia by clinical examination and neurophysiological studies including motor nerve conduction velocity, distal latency, electromyography and test for neuromuscular fatigue. After correction of anaemia there was a significant increase in motor nerve conduction velocity, a decrease in the duration of motor unit action potential, and a lessening of neuromuscular fatigue. We conclude that treatment of anaemia with r-HUEPO in patients with chronic renal failure undergoing haemodialysis may improve neuromuscular function.     

Aluminium overload and response to recombinant human erythropoietin in patients under chronic haemodialysis.

In this work, of 51 patients treated by rHuEpo, 25 were selected for study. The selection criteria were absence of clinically evident causes of anaemia other than end-stage renal failure, such as chronic infection, active systemic disease, bleeding sites, and vitamin B12 or iron deficiencies. Serum aluminum was assessed before dialysis and the presence of aluminium overload was confirmed by a DFO test. rHuEpo was given in a dose of 50 U/kg body-weight after each dialysis session three times weekly and the response to treatment was evaluated monthly for 8 months. Our data showed significant correlation between serum aluminum and the response to rHuEpo. The response was significantly greater in those with lower serum aluminium. We conclude that the aluminium load in chronic haemodialysis patients may have an effect on the response to rHuEpo.     

Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients.

BACKGROUND: Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the hypothesis that dialysate-related cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis fluids, differing in their microbiological quality, on the rHuEpo therapy. METHODS: Thirty male patients with end-stage renal disease maintained on regular haemodialysis were assigned either to a group treated with conventional (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online-produced ultrapure dialysate (group II). Randomization was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10-10.5 g/dl. Patients were followed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly and serum ferritin concentrations were determined at 6-week intervals. C-reactive protein (CRP) and interleukin-6 (IL-6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months. RESULTS: In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was associated with elevated surrogate markers (CRP, IL-6) of cytokine-induced inflammation. The switch from conventional to online-produced ultrapure dialysate in group II resulted in a lower bacterial contamination with a significant decrease of CRP and IL-6 blood levels. It was accompanied by a significant and sustained reduction of the rHuEpo dosage, which was required to correct the anaemia. Using multiple regression analysis, IL-6 levels are shown to have a strong predictive value for rHuEpo dosage in both groups. CONCLUSIONS: Our data demonstrate that dialysate-related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL-6. Dialysate-related cytokine induction might diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in a better response to rHuEpo. Not only would it save money, but it would also help to maintain an optimal haemoglobin level without further increase in rHuEpo dosage.     

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.     

Exercise tolerance after anaemia correction with recombinant human erythropoietin in end-stage renal disease

The aim of this study was to evaluate the effect of correction of chronic anaemia on the physical performance and the cardiovascular response to effort in children with end-stage renal disease (ESRD) maintained by haemodialysis. Seven patients (mean age 13.9 years) underwent triangular-type treadmill exercise testing before [haemoglobin (Hb) 6.3±0.9 g/dl] and after (Hb 11.2±1.2 g/dl) anaemia correction with recombinant human erythropoietin (rHuEPO). After treatment, the work-load reached, the peak oxygen uptake and average ventilatory anaerobic threshold (VAT) values were significantly increased (P<0.01,P<0.001,P<0.05 respectively). VAT values, expressed as a percentage of normal values, increased from 55.7±16.6% to 82.4±21%. This improvement correlated well with the increase in Hb (r=0.79). Oxygen pulse also increased significantly, when tested after anacmia correction. In conclusion, these data demonstrate that when the anaemia of children with ESRD is corrected with rHuEPO, there is a clear improvement in acrobic work capacity and effort tolerance.     

Low-dose aspirin does not prevent thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human erythropoietin

Treatment of the anaemia of renal disease with recombinant humanerythropoietin results in an improvement of haemostasis andan increased risk of thrombovascular accidents. In this prospective,placebo-controlled, double-blind, and cross-over study, theeffects of low-dose acetylsalicylic acid (30 mg daily) on thromboticand bleeding events during the initial period of treatment witherythropoietin in anaemic haemodialysis patients without previousthrombovascular accidents or known increased risk for thrombosiswere investigated. During correction of the haematocrit andthe first 3 months thereafter, group A (n = 68) received placeboand group B (n = 69) 30 mg acetylsalicylic acid daily. Cross-overtook place after the 3rd month of a stable haematocrit. Thestudy ended 3 months later. Target haematocrit (30–35%) was reached in 12.4±8 weeks (M ± SD). In group A the bleeding time was 382±285s, decreasing to 282±208 before cross-over (P<0.0l),and increasing to 395±271 (P<0.05) there after. Ingroup B the bleeding time was 390±381 s, 406±267(NS), and 285±238 (P<0.05) respectively. Twenty-twothrombovascular accidents were seen (16%, 13 during acetylsalicylicacid and 9 during placebo, NS), including 17 fistula thromboses.The incidence of bleeding events was not significantly differentbetween regimens. In conclusion, erythropoietin treatment resulted in a reductionof the bleeding time. When 30 mg acetylsalicylic acid was takenduring the treatment, the bleeding time did not decrease. Theregimen did not result in an increased number of bleeding events,but neither were thrombovascular accidents prevented in low-riskpatients.     

Intravenous versus subcutaneous administration of recombinant human erythropoietin in patients on haemodialysis and CAPD.

The most effective route of administration of rHuEpo is still a matter of discussion. Prospectively we studied subcutaneous (s.c.) versus intravenous (i.v.) administration in three comparable groups of patients; HD-s.c. (n = 9), HD-i.v. (n = 11), and CAPD-s.c. (n = 9). All the groups initially received 50 units/kg three times weekly. During the first 8 weeks dose adjustments were made only if target haemoglobin exceeded 11.3 g/dl (7 mM). Target haemoglobin was reached after 84 (42-98) days in the i.v. group and 42 (14-77) and 42 (28-56) respectively in the HD-s.c. and CAPD groups. The difference was statistically significant (P less than 0.05). Even the cumulative doses to reach target haemoglobin were significantly less in the two s.c. groups. To maintain haemoglobin at about 11.3 g/dl, weekly doses were as follows: HD-i.v. 125 U/kg (86-168), HD-s.c. 63 U/kg (20-85), and CAPD 72 U/kg (31-100). The total observation time after the target haemoglobin level was reached, was median 130 (114-264) days. The difference between the i.v. group and the two s.c. groups was statistically significant, (P less than 0.05) whereas there was no difference between the s.c. groups. We conclude that s.c. administration of rHuEpo is more effective in induction as well as in maintenance therapy and that s.c. administration is equally efficient in HD and CAPD patients.     

Long-term therapy with recombinant human erythropoietin increases CD8+ T-cell apoptosis in haemodialysis patients.

BACKGROUND: We intended to assess the intensity of apoptosis in the CD4+ and CD8+ T-lymphocytes of haemodialysis (HD) patients on recombinant human erythropoietin (rHuEpo). METHODS: The expression of Fas, tumour necrosis factor-alpha receptors (TNFRI and TNFRII) and the CD28 molecule on lymphocytes was evaluated in 15 HD patients before and during treatment with rHuEpo. In cultures of peripheral blood mononuclear cells (PBMCs) stimulated with rHuEpo, phytohaemagglutinin and camptothecin, our measures of apoptosis were the percentages of cells with subdiploid DNA content and of annexin V-stained cells. Results, Therapy with rHuEpo did not affect CD4+ T cells but decreased the percentage of CD8+ T cells in peripheral blood. The intensity of apoptosis in both CD4+ and CD8+ T cells at baseline was lower in HD patients than in healthy volunteers, and increased in those treated with rHuEpo. In vitro, rHuEpo did not induce apoptosis in PBMCs. The percentage of CD8+Fas+ T cells was constant, while that of CD8+TNFRI+ cells declined during follow-up. There was an increase in the percentage of CD28+ T cells, mainly in the CD8+ compartment, as early as 1 month after the introduction of rHuEpo. CONCLUSIONS: Treatment with rHupo caused a decline of CD8+ T cells in HD patients, which most probably was mediated via the TNFRI-related apoptotic pathway and was independent of Fas expression. Apoptosis in vitro was not directly influenced by rHuEpo, suggesting that the process in vivo was only initiated by rHuEpo supplementation.     

Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in haemodialysis patients.

Optimal route and frequency of administration of recombinant human erythropoietin (rHuEPO) have not yet been determined. There is some evidence to suggest that subcutaneous administration of rHuEPO may be more effective than the intravenous route in reversing renal anemia. It is also unclear whether rHuEPO is more effective when given by a large intermittent dose or by more frequent multiple divided doses. We have compared the effect of twice weekly versus once weekly subcutaneous administration of rHuEPO in two groups of haemodialysis patients. At the end of 12 weeks of treatment with rHuEPO, the mean haemoglobin levels had risen from 6.9 +/- (SD) 0.7 to 8.9 +/- 1.3 g/dl in the once weekly group and from 7.2 +/- 1.0 to 9.3 +/- 1.6 g/dl in the twice weekly group. The average doses of rHuEPO used during the study were 127 +/- 6 and 115 +/- 18 U/kg body weight/week for the once weekly and twice weekly groups, respectively. Subcutaneous administration of low-dose rHuEPO is effective in reversing renal anaemia. Similar responses were obtained with once weekly and twice weekly regimens.     

Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).

BACKGROUND: Darbepoetin alfa is an erythropoietic agent with a 3-fold longer elimination half-life than recombinant human erythropoietin (rHuEpo), which allows less frequent dosing. This study investigated the safety and efficacy of darbepoetin alfa for treating anaemia in dialysis patients, using a dosing regimen that was independent of the patient's body weight (unit dosing). METHODS: Dialysis patients (n=341) maintained on rHuEpo treatment (alfa or beta) were switched to darbepoetin alfa at a reduced dosing frequency, but by the same route of administration [intravenous (i.v.) or subcutaneous (s.c.)]. Patients receiving rHuEpo two or three times weekly changed to once-weekly darbepoetin alfa, and those receiving rHuEpo once weekly changed to once every other week darbepoetin alfa. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations within -1.0 and +1.5 g/dl of the individual mean baseline haemoglobin and between 10 and 13 g/dl for 24 weeks. RESULTS: Mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was 0.13 g/dl (95% CI, 0.01, 0.25), which was not clinically relevant. An analysis by route of administration revealed that mean haemoglobin concentrations had increased by 0.58 g/dl (95% CI, 0.33, 0.82) in patients receiving i.v. darbepoetin alfa, and previously treated with i.v. rHuEpo, while remaining unchanged in s.c. patients (0.00 g/dl; 95% CI, -0.13, 0.13) previously treated by s.c. rHuEpo. In addition, there was a statistically significant decrease in mean weekly i.v. darbepoetin alfa dose requirements from 25.2 microg/week at baseline to 21.5 microg/week (P=0.004) during the evaluation period (-17.3%). Subcutaneous weekly dosage requirements increased slightly during the study period (20.8 to 22.7 microg/week; P=0.014). An i.v./s.c. dose ratio of 0.95 (95% CI, 0.78, 1.14) at evaluation confirms previous findings that dose requirements by the i.v. and s.c. routes were not different in patients treated with darbepoetin alfa. Haemoglobin concentrations were also effectively maintained in patients who received darbepoetin alfa once weekly and once every other week. Darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia in dialysis patients with unit doses of darbepoetin alfa effectively and safely maintains target haemoglobin concentrations with less frequent dosing. Dose requirements for darbepoetin alfa following i.v. and s.c. administration were not different. The results of this study demonstrate that darbepoetin alfa administered i.v. once weekly, or once every other week is an effective treatment regimen for haemodialysis patients with renal anaemia.     

Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo)

Nephrol Dial Transplant     

The benefits of treatment with recombinant human erythropoietin in cancer patients

IMPROVED QUALITY OF LIFE WITH EPOETIN BETA: In a study against a placebo, there was evidence that the quality of life scores were significantly improved in patients treated with epoetin beta, whether they exhibited a solid tumour or a malignant lymphoma. The same was noted in children with cancer exhibiting severe neoplasia and treated with chemotherapy. The efficacy and tolerance to treatment were equivalent, whatever the administration regimen. IN PATIENTS SUFFERING FROM MYELODYSPLASTIC SYNDROMES: A particular entity among malignant blood diseases, myelodysplastic syndromes are at the origin of anaemia against which repeated transfusions and growth factors are proposed with varying results and disadvantages, and against which erythropoietin may be moderately effective (a mean of 25% in non-selected cohorts of patients). DEPENDING ON THE PROTOCOLS OF ERYTHROPOIETIN ADMINISTRATION IN CASES OF MYELODYSPLASTIC SYNDROMES: Recombinant human erythropoietin, irrespective of its concentration in myelodysplastic cell culture, does not appear capable of restoring normal erythropoiesis. The influence of prolonged treatment is not admitted by all. The effects of the addition of growth factors (notably G-CSF) are obvious but some are controversial because of the costs and the prolonged duration of such treatments.