The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia.

BACKGROUND: Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. METHODS: After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. RESULTS: The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.     

Dose of epoetin alfa used in haemodialysis patients when switching from subcutaneous to intravenous administration

AIM: To determine whether there is a change in the dose of epoetin alfa when switching from subcutaneous (SC) to intravenous (IV) administration in Australian haemodialysis patients. METHODS: Validated data from 2214 haemodialysis patients at 16 Australian hospitals who switched from SC to IV administration of epoetin alfa from January 2002 to September 2003 were extracted from the Renal Anaemia Management database provided by Janssen-Cilag. Of these patients, 806 had dosing data for at least 1 month before switch through to 6 months post switch (6 month cohort). RESULTS: In the 6 month cohort, the mean dose was 10 776 IU/week (95% CI: 10 235, 11 317) at switch compared with 12 008 IU/week (95% CI: 11 447, 12 569) 6 months post switch, an increase in a dose of 1232 IU/week (95% CI: 868, 1596). The mean haemoglobin levels at switch were 11.55 g/dL (95% CI: 11.45, 11.66) compared with 11.59 g/dL (95% CI: 11.49, 11.68) 6 months after switch. Centre and dosing frequency of epoetin alfa before switch were determinants of increased dose. CONCLUSION: Changing from SC to IV administration of epoetin alfa resulted in an 11% increase in mean dose to maintain haemoglobin levels in Australian haemodialysis patients.     

Randomized trial on the therapeutic equivalence between Eprex and GerEPO in patients on haemodialysis

Aim: Treatment of renal anaemia with epoetin is well established. However, epoetin is expensive. Biogeneric epoetin with proven efficacy would reduce cost and improve access to therapy. We conducted this first ever comparative study of a biogeneric and the original product. Methods: Stable haemodialysis patients with haemoglobin (Hb) of at least 9 g/dL and receiving the human recombinant erythropoietin Eprex were randomized to continue Eprex or convert to GerEPO, a biogeneric epoetin, for 12 weeks. The primary efficacy variable was a change in Hb from baseline. Results: Ninety-three subjects were randomized to each arm. Ninety-two and 87 subjects on the Eprex and GerEPO arms, respectively, completed the trial. Mean Hb in both groups declined over time. The mean decline in Hb was -0.47 g/dL in the Eprex group and -0.45 g/dL in the GerEPO group. The mean difference in the change in Hb from baseline to week 12 between the two groups was 0.02. The 95% confidence interval was -0.42 to 0.46, which lies within the margin of equivalence (+/-0.5 g/dL). The results of intention-to-treat analysis were similar. There were no significant differences in the epoetin dose, iron therapy or iron stores between the groups. Patients receiving GerEPO reported more adverse events. Conclusion: GerEPO was therapeutically equivalent to Eprex with respect to Hb response for patients with Hb in the subtherapeutic target range as is common in this study population. The trial duration was insufficient for safety evaluation, which must await further investigation. More biogeneric products should be subjected to rigorous evaluation.     

Darbepoetin alpha in lower-than-equimolar doses maintains haemoglobin levels in stable haemodialysis patients converting from epoetin alpha/beta.

BACKGROUND: The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable. METHODS: Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period. RESULTS: One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, P<0.0001), yielding a mean final conversion ratio of 1:336. A dose decrease was observed in 56 patients, no dose change in 28 and an increase in 16 patients. Dose reduction strongly depended on baseline epoetin dose: no dose reduction was required for baseline epoetin doses <5000 U/week, whereas a 37% lower mean dose was necessary for baseline doses of 7000-10 000 U/week. The darbepoetin alpha dose reduction did not depend on the previous epoetin type (alpha or beta) or the previous epoetin administration route (i.v. vs s.c.). CONCLUSIONS: The mean darbepoetin alpha dose needed to keep Hb stable in patients previously treated with epoetin is significantly lower than the equimolar dose. Although the equimolar 1:200 conversion ratio is appropriate for lower epoetin doses (<5000 IU/week), the darbepoetin dose for patients converting from >or=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings.     

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients

BACKGROUND: Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. METHODS: This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. RESULTS: Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. CONCLUSIONS: This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.     

Comparison of the therapeutic efficacy of epoetin beta and epoetin alfa in maintenance phase hemodialysis patients

In May 2009 for financial reasons, the epoetin product used for hemoglobin (Hb) maintenance in our renal dialysis unit was changed from epoetin beta to epoetin alfa. Although widely believed that the dosage requirements are the same, we undertook a retrospective analysis to investigate whether the dosage requirements in chronic renal failure patients were comparable for both preparations. We studied 128 stable end-stage renal failure patients on hemodialysis (three times per week) receiving erythropoietin therapy to maintain their Hb at 11-12.5 g/dL. Patients were excluded if within the study period they developed signs of infection, bleeding, required blood transfusion, were under-dialyzed, or required hospital admission. Regular monthly Hb concentrations and hematocrit (Hct) levels were measured for each patient. The weekly EPO index (defined as weekly epoetin dose/mean monthly Hct) was derived for each patient, before and after regime change. Of the 128 patients in end-stage renal failure, 79 were included in the study. There was no significant difference between the two preparations in terms of Hct level achieved (p = 0.15). However, the median weekly epoetin dose requirement increased from 6733 (range 750-30,000) IU/week to 9000 (250-30,667) IU/week (p < 0.001). EPO index similarly increased from 20,465 (2500-130,846) IU/week/% to 27,073 (729-98,937) IU/week/% (p < 0.001). Our study showed that a higher dose of epoetin alfa was needed to maintain target Hb concentration.     

Fluctuations in haemoglobin levels in haemodialysis, pre-dialysis and peritoneal dialysis patients receiving epoetin alpha or darbepoetin alpha

Aim: To characterize the haemoglobin variability of haemodialysis, peritoneal dialysis and pre‐dialysis patients treated with either epoetin alpha or darbepoetin alpha in a clinical setting where treatment was administered according to current standard Australian practice. Methods: Data on haemodialysis, pre‐dialysis and peritoneal dialysis patients were extracted from the Renal Anaemia Management database (RAM) from 1 January 2001 to 31 December 2004. The variance in haemoglobin was calculated from patient records with more than five haemoglobin observations over a period of at least 4 weeks following 9 weeks of therapy. A mixed‐model was fitted to the within‐patient variances and weighting was based on the number of observations minus 1 for each record. Results: The mean within‐patient variance in haemoglobin levels for i.v. administered erythropoietin‐stimulating agents (IV) haemodialysis, s.c. administered erythropoietin‐stimulating agents (SC) haemodialysis, predialysis_SC and peritoneal dialysis_SC patients receiving epoetin alpha were 9% (95% CI: 13% to 5%, P < 0.0001), 17% (95% CI: 32% to 0.2%, P = 0.047), 19% (95% CI: 27% to 11%, P < 0.0001) and 26% (95% CI: 33% to 18%, P < 0.0001) lower than that for patients receiving darbepoetin alpha. The mean haemoglobin levels for haemodialysis_IV, haemodialysis_sc predialysis_SC and peritoneal dialysis_SC patients receiving darbepoetin alpha were 11.6 g/dL, 11.2 g/dL, 11.5 g/dL and 11.5 g/dL compared with 11.5 g/dL, 11.6 g/dL, 11.7 g/dL and 11.5 g/dL for patients receiving epoetin alpha. Conclusion: There was 9–26% greater within‐patient fluctuation in haemoglobin levels in patients receiving darbepoetin alpha compared with epoetin alpha. The causes of haemoglobin fluctuations and the implications for patient outcomes and resource use require further study.     

Epoetin alfa and darbepoetin alfa: effects on ventricular hypertrophy in patients with chronic kidney disease

BACKGROUND: Anemia is very common in chronic kidney disease (CKD) and is commonly treated with recombinant human erythropoietin. The aim of this study was to analyze the efficacy of epoetin alfa and darbepoetin alfa on left ventricular parameters in patients with CKD. METHODS: Patients with CKD not yet dependent on dialysis were randomly assigned to treatment with epoetin alfa at weekly intervals (Epo group; baseline hemoglobin 8.5 +/- 0.8 mg/dL, creatinine clearance 10.0 +/- 2.0 ml/min per 1.73 m2) or darbepoetin alfa every 2 weeks (Dar group; baseline hemoglobin 8.2 +/- 0.8 mg/dL, creatinine clearance 10.8 +/- 2.4 ml/min per 1.73 m2). Patients not receiving erythropoietin served as a control group. Two-dimensional color Doppler echocardiography was performed at baseline and at 24 weeks to measure left ventricular mass index (LVMI) and ejection fraction. RESULTS: Hemoglobin in the 2 treatment arms was corrected to 10.6 +/- 0.6 mg/dL and 10.7 +/- 0.5 mg/dL for Epo and Dar groups, respectively. The LVMI decreased significantly in both the Epo (-5.7 +/- 14.2 g/m2) and the Dar group (-5.6 +/- 15.8 g/m2) but increased in the control group (9.0 +/- 15.1 g/m2; p=0.02, between the Epo and control groups, and between the Dar and control groups). The ejection fraction was increased in both treatment groups (Epo group: 2.45% +/- 2.28%, Dar group: 1.64% +/- 2.95%) and decreased in controls (-1.15% +/- 3.69%) (p=0.004 among groups). The 2 treatment groups showed similar efficacy. The degree and the change of renal function did not differ among the 3 groups at end of study. CONCLUSIONS: The 2 erythropoiesis-stimulating agents epoetin alfa and darbepoetin alfa, when given to patients with CKD in doses aimed at standard anemia correction are associated with a similar degree of LVMI reduction, in the absence of a concomitant enhancement of CKD progression.     

Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: the PROMPT study

AIM: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). METHODS: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. RESULTS: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). CONCLUSIONS: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.     

Erythropoietin alone or as an adjuvant for the autologous blood donation program in major orthopedic surgery

BACKGROUND: Patients with anemia undergoing elective joint replacement are often excluded from preoperative autologous donation (PAD). The purpose of this study was to compare the efficacy of preoperative erythropoietin (epoetin alpha) as an adjuvant treatment to PAD versus preoperative erythropoietin alfa alone in patients with mild anemia undergoing major orthopedic surgery. PATIENTS AND METHODS: The study enrolled 75 patients scheduled for total joint arthropalsty of the hip or knee or spinal surgery and with a hemoglobin (Hb) concentration between 10 and 13 g/dL. Group 1 patients were assigned to receive weekly doses of subcutaneous epoetin alpha (40,000 IU) 21, 14, and 7 days before surgery and to participate in the PAD program; group 2 patients were excluded from the PAD program and received 2 doses of epoetin alpha every week over the same period. RESULTS: Group 1 (n = 39) and group 2 (n = 36) were similar with respect to patient characteristics, biological parameters, and surgical procedures, In group 1, mean preoperative Hb rose fom 12.5 g/dL to 12.8 g/dL, patients received a mean 5.1 doses of epoetin alpha, and they gave a mean 1.9 units of autologus blood and 1 received allogenic blood. In group 30.7% received transfusions of autologous blood and 1 received allogenic blood. In group 2, preoperative Hb increased from 11.7 g/dL to 13.5 g/dL, patients received 3.8 doses of epoetin alpha, and 3 were transfused with allogenic blood (P > 0.05). CONCLUSION: Epoetin alpha alone and erythropoietin as a adjuvant to a PAD program are equally effective in reducing allogenic transfusion during hip and knee arthroplasty and spinal column surgery of up to 3 spaces.     

Varying intervals of subcutaneous epoetin alfa in hemodialysis patients

BACKGROUND: The optimal subcutaneous (SC) epoetin alfa strategy is unestablished. The individual variability in dose requirements needs consideration. In this study, prolonged intervals were assessed in relation to varying dose requirements. METHODS: The study included 153 hemodialysis (HD) patients on stable SC epoetin alfa. Based on dose requirements, the patients received either 4,000 U (group I, n=51) or 10,000 U (group II, n=102) as whole 1 mL vials at prolonged intervals. The study comprised three 8-week periods: an initial period maintaining the basal regimens, an adjustment period where the intervals were prolonged, and a maintenance period. Alterations in hemoglobin (Hb), weekly doses and intervals in each group were compared. RESULTS: One hundred and thirty-seven patients completed the study (48 in group I and 89 in group II). In group I, the mean interval was prolonged from 5.4 +/- 1.9 to 7.8 +/- 3.1 days (p=0,01) with stable Hb and EPO doses. In group II, prolonged intervals were associated with a reduction in mean Hb below target level and a significant increase in EPO doses (p=0,002). Iron deficiency and inflammation could explain the poor response in approximately one-third of the patients. CONCLUSIONS: In HD patients, the optimal injection frequency should be individually adjusted. Prolonged intervals can be applied to patients with low-dose requirements. Observing iron status and inflammation is necessary for optimal response.     

A randomized, double-blind, placebo-controlled study to assess the effect of recombinant human erythropoietin on functional outcomes in anemic, critically ill, trauma subjects: the Long Term Trauma Outcomes Study

BackgroundAchieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy.MethodsPatients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge.ResultsOne hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups.ConclusionsNo differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.     

A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.     

Hemoglobin Level Variability in Renal Transplant Patients Treated With Erythropoiesis Stimulating Agents

Objective

Treatment with erythropoiesis stimulating agents (ESA) is associated with fluctuations in hemoglobin (Hb) levels. Recently, variability of Hb has been considered a factor that influences comorbidity and mortality among hemodialysis patients. The purpose of this analysis was to describe the phenomenon of Hb variability during ESA treatment, to study associated factors among kidney transplant patients, and to assess the impact on patient and graft survivals.

Patients and Methods

Hb variability (defined as fluctuations of Hb ± 1.5 g/dL) was assessed in 85 renal transplant patients treated with ESA for at least 3 months and with a minimum of 6 Hb measurements during 1 year.

Results

Fifty-eight percent of the patients experienced Hb variability during follow-up. Only 3% of patients maintained stable Hb levels within the target range (11-13 g/dL), although 83% of patients maintained Hb levels >11 g/dL. Multivariate analysis showed that the clinical factors associated with variability were changes in ESA dose (relative risk [RR]: 2.92; 95% confidence interval [CI]: 1.0-8.5; P < .05), infectious events with hospitalization (RR: 1.95; 95% CI: 1.23-2.13; P < .05), and the use of sirolimus (RR: 1.1; 95% CI: 1.0-3.6; P < .05). When dose changes and hospitalization were excluded from the analysis, variability was an independent predictor of worsening graft function.

Conclusions

Hb variability is common in renal transplant patients treated with ESA. Only a few patients maintained Hb levels within the therapeutic range, although most had levels >11g/dL. Dose changes, inflammatory status, and worsening graft function are the determining factors of variability. Variability had no influence on patient survival, although it was a marker of worsening graft function.     

Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients.

BACKGROUND: Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period. METHODS: We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin. RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period. CONCLUSIONS: Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.     

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.     

The new rHuEPO alpha (epotin) in the management of anemia of end-stage renal disease in patients on maintenance hemodialysis

Recombinant human erythropoietin has proved to be effective to treat anemia of end-stage renal disease (ESRD). The aim of this study was to assess the efficacy and safety profile of Epotin, a rHuEPO produced in the Middle East. One hundred thirty patients with Hct 相似文献   

C.E.R.A. maintains stable hemoglobin in Latin American patients on dialysis

Background

C.E.R.A. is a continuous erythropoietin receptor activator with characteristics that permit a once-monthly schedule of administration for the maintenance treatment for chronic kidney disease (CKD) patients. The main objective of this study was to assess the maintenance of Hb concentration with once-monthly intravenous and/or subcutaneous C.E.R.A. therapy in Latin American dialysis patients with chronic renal anemia previously treated with epoetin alfa s.c or i.v 1–3 times per week.

Methods

This was a single-arm, open-label, multicenter, 32-week study of anemic patients with CKD previously treated with epoetin alfa sc or iv 1–3 times per week. After a 4-week screening period, during which mean Hb levels were maintained between 10.5 and 12.5 g/dL on their previous erythropoiesis stimulating agent, eligible patients entered a 16-week C.E.R.A. dose titration period followed by a 4-week efficacy evaluation period (EEP) and a 28-week safety follow-up. The starting dose of C.E.R.A. was based on the previous dose of epoetin alfa. Doses of C.E.R.A. were then adjusted to maintain Hb levels within ±1.0 g/dL of the reference concentration and between 10.5 and 12.5 g/dL. The Hb reference concentration was defined as the mean of all Hb levels during screening. The primary end point was the proportion of patients maintaining a mean Hb concentration (g/dL) within ±1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the EEP.

Results

A total of 163 patients from 27 centers in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay, and Venezuela entered the treatment period and 102 completed the prescribed course of C.E.R.A. Forty-five patients (43.7 %) maintained a mean Hb concentration within ±1 g/dL of their reference Hb value and between 10.5 and 12.5 g/dL during the EEP. The median monthly dose remained constant at 120 μg during the titration period and during the EEP. On the average, there were only 2.3 dose changes per patient in 28 weeks of treatment, covering 7 C.E.R.A. scheduled administrations. 53 % of all dose changes were dose decreases, 47 % increases. A total of 10 AEs and 4 SAEs were considered to be related to the study treatment.

Conclusions

Once-monthly C.E.R.A. treatment effectively maintains stable Hb concentrations in patients with chronic renal anemia undergoing dialysis with a good safety and tolerability profile.     

Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Anemia is common in diabetics with nephropathy; however, the impact of anemia on progression to ESRD has not been carefully examined. METHODS: We studied the relationship between baseline hemoglobin concentration (Hb) and progression of diabetic nephropathy to ESRD in 1513 participants enrolled in Reduction in Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study and followed for an average of 3.4 years. Multivariate Cox proportional hazards models were used to analyze the relationship between Hb and ESRD, after adjusting for predictors for ESRD. Analyses were performed with Hb stratified by quartile: first quartile <11.3 g/dL, second quartile 11.3 to 12.5 g/dL, third quartile 12.6 to 13.8 g/dL, and fourth quartile >/=13.8 g/dL (reference) and as a continuous variable. RESULTS: Baseline hemoglobin concentration was correlated with subsequent development of ESRD. After adjustment for predictors of ESRD, the hazard ratios for the first, second, and third Hb quartiles were 1.99 (95% CI, 1.34-2.95), 1.61 (95% CI 1.08-2.41), and 1.87 (95% CI 1.25-2.80). With hemoglobin as a continuous variable, the adjusted hazard ratio was 0.90 (95% CI 0.84-0.96, P= 0.0013). The average increase in adjusted relative risk was 11% for each 1 g/dL decrease in hemoglobin concentration. CONCLUSION: Our data suggest that even mild anemia, Hb <13.8 g/dL increases risk for progression to ESRD. Hemoglobin is an independent risk factor for progression of nephropathy to ESRD in type 2 diabetes.