Subcutaneous Recombinant Human Erythropoietin Research Articles

EFFECT OF SUBCUTANEOUS RECOMBINANT HUMAN ERYTHROPOIETIN ON BLOOD PRESSURE IN PRE-DIALYSIS CHRONIC KIDNEY DISEASE (CKD) PATIENTS

Objective: To determine the effect of subcutaneous recombinant human erythropoietin on blood pressure in predialysis chronic kidney disease (CKD) patients.
 Study Design: Case-series descriptive study.
 Place and Duration of Study: Combined Military Hospital Peshawar, from Mar 2016 to Sep 2016.
 Methodology: A total of 100 cases were enrolled. Inclusion criteria was patients of 18 to 60 years of both gender & estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 having Hb <10g/dL and pre-dialysis while Exclusion Criteria was pregnancy or lactation, BP more than 140/90 mmHg, patients on Haemodialysis and worsening renal function. Baseline BP, body weight and eGFR of anaemic chronic kidney disease patients were recorded prior to EPO Alpha therapy. Erythropoiesis-stimulating agents (ESAs) i.e. EPO Alpha (50-100 Units/kg thrice or once weekly) was administered subcutaneously. Subsequent blood pressure, body weight and eGFR monitoring was done after 2 and 4 weeks post EPO Alpha injection.
 Results: Mean age range was 46.71 years with range of 20-60 years, 73 (73%) were male while 27 (27%) werefemales. Mean ± SD for other quantitative variables like eGFR was 23.12 ± 5.28, Hb levels (g/dL) was 8.62 ± 0.85,Weight (kg) was 56.66 ± 6.62 and duration of CKD was 9.87 ± 4.02. Frequency of Hypertension (post EPO) was 2(2%) and p-value was 0.453.
 Conclusion: We concluded that the frequency of hypertension in pre-dialysis patients with chronic kidney disease (CKD) receiving recombinant human erythropoietin (rhEPo) subcutaneously (SC) in low doses, is very low, so rhEPo can be used subcutaneously......................

Outcomes with the Use of Recombinant Human Erythropoietin in Critically Ill Burn Patients

Recent data demonstrate a possible mortality benefit in traumatically injured patients when given subcutaneous recombinant human erythropoietin (rhEPO). The purpose of this report is to examine the effect of rhEPO on mortality and transfusion in burn patients. We conducted a review of burn patients (greater than 30% total body surface area, intensive care unit [ICU] days greater than 15) treated with 40,000 u rhEPO over an 18-month period (January 2007 to July 2008). Matched historical controls were identified and a contemporaneous cohort of subjects not administered rhEPO was used for comparison (NrhEPO). Mortality, transfusions, ICU and hospital length of stay were assessed. A total of 105 patients were treated (25 rhEPO, 53 historical control group, 27 NrhEPO). Hospital transfusions (mean 13,704 +/- mL vs. 13,308 +/- mL; P = 0.42) and mortality (29.6 vs. 32.0%; P = 0.64) were similar. NrhEPO required more blood transfusions (13,308 +/- mL vs. 6827 +/- mL; P = 0.004). No difference in mortality for the rhEPO and NrhEPO (32.0 vs. 22.2%; P = 0.43) was found. Thromboembolic complications were similar in all three groups. No effect was seen for rhEPO treatment on mortality or blood transfusion requirements in the severely burned.

Randomized Equivalence Study Evaluating the Possibility of Switching Hemodialysis Patients Receiving Subcutaneous Human Erythropoietin Directly to Intravenous Darbepoetin Alfa

Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used either intravenously or subcutaneously with no dose penalty; however, the direct switch from subcutaneous recombinant human erythropoietin (rHuEPO) to intravenous darbepoetin has barely been studied. To establish the equivalence of a direct switch from subcutaneous rHuEPO to intravenous darbepoetin versus an indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin in patients undergoing hemodialysis. In this open, randomized, 6-month, prospective study, patients with end-stage kidney disease who were on hemodialysis were randomized into 2 groups: direct switch from subcutaneous rHuEPO to intravenous darbepoetin (group 1) and indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin (group 2). A third, nonrandomized group (control), consisting of patients treated with intravenous rHuEPO who were switched to intravenous darbepoetin, was also studied to reflect possible variations of hemoglobin (Hb) levels due to change from one type of ESA to the other. The primary outcome was the proportion of patients with stable Hb levels at month 6. Secondary endpoints included Hb stability at month 3, dosage requirements for darbepoetin, and safety of the administration route. Among 154 randomized patients, the percentages with stable Hb levels were equivalent in groups 1 and 2, respectively, at month 3 (86.0% vs 91.3%) and month 6 (82.1% vs 81.6%; difference -0.5 [90% CI -12.8 to 11.8]). Mean Hb levels between baseline and month 6 remained stable in both groups, with no variation in mean darbepoetin dose. Mean ferritin levels remained above 100 microg/L in the 3 groups during the whole study, and darbepoetin was well tolerated. This study has shown equivalent efficacy on Hb stability without the need for dosage increase in patients switched directly from subcutaneous rHuEPO to intravenous darbepoetin.

Factors Influencing Route of Administration for Epoetin Treatment Among Hemodialysis Patients in the United States

Published clinical guidelines advocate subcutaneous (SC) administration for epoetin therapy, although this is practiced among only 7% of all hemodialysis patients. Despite this disparity, few studies have examined factors associated with route of epoetin administration in hemodialysis patients. Data from the Centers for Medicare & Medicaid Services End-Stage Renal Disease Clinical Performance Measures Project were used to identify 13,854 patients receiving hemodialysis in 3,069 dialysis facilities from October to December in 1999 and 2000. Unadjusted associations were examined by using t-test and chi-square test. Adjusted associations were estimated by using generalized estimating equations to control for clustering of patients within the same dialysis facility. In the United States, use of the SC route of epoetin administration varies widely across the country. After adjusting for patient sociodemographics and comorbidities, the greatest rates of SC therapy are found in the Midwest and West, in providers not affiliated with chains, and in hospital-based and not-for-profit freestanding units. Previous exposure to SC administration (as a predialysis or peritoneal dialysis patient) predicted subsequent SC use, for-profit and large chains were significantly less likely to use SC administration, and increased use of injectable drugs overall (to maximize income) was associated with less SC use. In addition to regional variation in SC use, study findings indicate that physician decision making for epoetin administration route is influenced primarily by type of ownership and financial incentives. Adherence to published clinical guidelines was not a consistent predictor of SC use. Given the similar effectiveness, but significantly decreased dose associated with SC epoetin, these findings suggest an enormous opportunity for cost savings for the Medicare program.

A rationale for an individualized administration frequency of epoetin beta: a clinical perspective.

The efficacy and safety of intravenous (i.v.) and subcutaneous recombinant human erythropoietin (rh-EPO, epoetin) for the treatment of renal anaemia is well established. Subcutaneous administration of epoetin is recommended by current guidelines because it is more flexible and convenient than i.v. dosing, enables dose reduction of epoetin and results in cost benefits. Subcutaneous administration of epoetin beta permits flexible dosing regimens that can be tailored to patients' individual needs. This was demonstrated in a recent, large, randomized, controlled trial in which once-weekly dosing of epoetin beta was as effective as the same total dose administered two or three times weekly. New developments in delivery devices for self-administration, which are more convenient and acceptable to patients, also contribute to the ability to individualize treatment. Furthermore, educating patients in the management of renal anaemia encourages collaboration between patients and health care providers, enabling more tailored treatment regimens to be developed. In conclusion, the use of flexible dosing frequencies, easy-to-use delivery devices and patient education may increase patient compliance and encourage self-administration of epoetin beta. The ability to individualize epoetin beta therapy increases the number of options available to nephrologists and their patients, leading to greater opportunities to tailor treatment according to specific needs.

PHARMACOKINETICS OF SEVERAL SUBCUTANEOUS DOSES OF ERYTHROPOIETIN: POTENTIAL IMPLICATIONS FOR BLOOD TRANSFUSION

1. The aim of the present study was to assess the effectiveness of repeated subcutaneous low-dose recombinant human erythropoietin (rHuEPO) on parameters associated with improved procurement of autologous blood; a procedure regularly used to preclude the need for homologous blood transfusion at the time of elective surgery. 2. Three groups of three volunteers each (n = 9) were administered one of three low doses of rHuEPO (30, 60 or 100 IU/kg bodyweight, s.c.) on days 1, 4 and 8. The plasma pharmacokinetic profile of rHuEPO was studied after the first and third injections. Statistical evaluations were intragroup and intraindividual comparisons. 3. There was a linear relationship between maximum plasma concentration (Cmax) and dose. In the overall study group, Cmax and area under the curve (AUC) were significantly decreased, while the mean residence time (MRT) and elimination half-life (t1/2beta) were significantly increased on day 8 relative to day 1. Significant and sustained increases in reticulocytes were observed after rHuEPO administration, which were maintained above the predose values throughout the study period. 4. In conclusion, rHuEPO, by subcutaneous repeat-dose, was eliminated more slowly and remained longer in the circulation, despite lowered plasma concentrations. Repeated low rHuEPO administration at doses > or = 60 IU/kg bodyweight stimulated modest but sustained reticulocyte concentrations, suggesting that cost may be substantially decreased in autologous blood donation or perioperative treatment programmes.

Effect and cost of subcutaneous recombinant human erythropoietin in preoperative patients.

Effect and cost of subcutaneous recombinant human erythropoietin in preoperative patients.

Comparison between Intravenous and Subcutaneous Recombinant Human Erythropoietin (Epoetin Alfa) Administration in Presurgical Autologous Blood Donation in Anemic Rheumatoid Arthritis Patients Undergoing Major Orthopedic Surgery

Comparison between Intravenous and Subcutaneous Recombinant Human Erythropoietin (Epoetin Alfa) Administration in Presurgical Autologous Blood Donation in Anemic Rheumatoid Arthritis Patients Undergoing Major Orthopedic Surgery

Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study.

According to this facility's protocol for the treatment of anemia in hemodialyzed patients, androgens were administered to male patients aged over 50 yr and recombinant human erythropoietin was administered to male patients below 50 yr of age and to female patients. In the study presented here, both therapeutic approaches have been prospectively analyzed. Patients were divided into two groups. Group A was composed of 18 patients, aged 62 +/- 12 yr, treated with nandrolone decanoate (200 mg/wk im) for 6 months; Group B was composed of 22 patients (6 men, 16 women) aged 47 +/- 15 yr, treated with subcutaneous recombinant human erythropoietin (initial dose, 6000 IU/wk) for 6 months. The increases of hemoglobin were similar in both groups; Group A, from 7.3 +/- 0.8 to 10.8 +/- 1.7 g/dL (P < 0.001), and Group B, from 7 +/- 0.6 to 10.4 +/- 1 g/dL (P < 0.001). In Group A, increases of triglycerides (159 +/- 71 versus 267 +/- 153 mg/dL, P < 0.001), serum albumin (3.9 +/- 0.3 versus 4.2 +/- 0.3 g/dL, P < 0.05), and dry weight (62.1 +/- 9.8 versus 64.9 +/- 10.1 kg, P < 0.001) were observed, which remained unmodified in Group B. Blood pressure control worsened in one patient (6%) from Group A, and in ten patients (45%) from Group B (P < 0.05). In conclusion, androgens produced an improvement in anemia in selected patients, similar to that achieved by use of recombinant human erythropoietin but at a lower cost. Androgens also have an appreciable anabolic effect and did not increase the blood pressure.

Subcutaneous recombinant erythropoietin in preterminal renal insufficiency

Recombinant human erythropoietin was given to eight children and adolescents with stable chronic renal failure in the predialysis state. The hormone was administered subcutaneously, twice weekly for 12 weeks, at a starting dose of 50 U/kg per week. The dosage was adapted evekry 4th week. Target haemoglobin was 10.5–11.5 g/dl, and the target haematocrit 32%–35%. Baseline haemoglobin levels of 8.20±0.93 g/dl increased to 9.17±1.10, 10.38±1.18 and 11.19±0.84 g/dl (mean±SD) after 4, 8 and 12 weeks respectively. Serum ferritin levels decreased progressively despite iron supplementation. No side-effects were observed: creatinine clearances remained stable, blood pressure did not increase and none of the patients displayed either convulsions or thrombotic features. The study shows that subcutaneous recombinant human erythropoietin is both effective and safe in anaemic children and adolescents with chronic renal insufficiency.

Subcutaneous recombinant erythropoietin in preterminal renal insufficiency.

Recombinant human erythropoietin was given to eight children and adolescents with stable chronic renal failure in the predialysis state. The hormone was administered subcutaneously, twice weekly for 12 weeks, at a starting dose of 50 U/kg per week. The dosage was adapted every 4th week. Target haemoglobin was 10.5-11.5 g/dl, and the target haematocrit 32%-35%. Baseline haemoglobin levels of 8.20 +/- 0.93 g/dl increased to 9.17 +/- 1.10, 10.38 +/- 1.18 and 11.19 +/- 0.84 g/dl (mean +/- SD) after 4, 8 and 12 weeks respectively. Serum ferritin levels decreased progressively despite iron supplementation. No side-effects were observed: creatinine clearances remained stable, blood pressure did not increase and none of the patients displayed either convulsions or thrombotic features. The study shows that subcutaneous recombinant human erythropoietin is both effective and safe in anaemic children and adolescents with chronic renal insufficiency.

Efficacy of Once- versus Thrice-Weekly Subcutaneous Recombinant Human Erythropoietin in Children Receiving Continuous Cycling Peritoneal Dialysis

The subcutaneous administration of recombinant human erythropoietin is effective in the treatment of anemia of end-stage renal disease. Single-dose pharmacokinetic studies suggest the possibility of less frequent dosing via the subcutaneous route. In this study, dosing once-weekly was as effective as thrice-weekly subcutaneous dosing in maintaining the corrected hematocrit in a group of children receiving continuous cycling peritoneal dialysis. This regimen was preferred by and beneficial to both patients and their parents.

Subcutaneous recombinant human erythropoietin in children with renal anemia on continuous ambulatory peritoneal dialysis.

Subcutaneous recombinant human erythropoietin (rHuEpo) treatment of renal anemia was performed in four boys and eight girls on CAPD, aged 0.8-12.5 (mean 7.4) years. In contrast to previous studies, our therapeutic goal was not set with a hematocrit of 30% but with full correction of anemia. Following a maximum weekly rHuEpo dosage of median 120 (range 100-240) IU/kg body weight, hematocrit increased in 10 children from 24 (14-29)% within 12 (4-17) weeks to 40.1 (33.5-48.4)%. The weekly increase in hematocrit was 1.27 (0.5-3.1)%. The corrected reticulocyte count increased from 1.3 (0.7-1.8)% to 2.3 (1.4-3.9)% within 4 (2-6) weeks. Eight children fulfilled the protocol; six with an uncomplicated course were able to maintain a hematocrit of 37.1 (35.1-42.7)% with only one sc medication per week of approximately two-thirds of their highest weekly rHuEpo dosage. No serious adverse effect of rHuEpo therapy was observed.

The efficacy of subcutaneous recombinant human erythropoietin in the correction of phlebotomy-induced anemia in autologous blood donors.

The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3-week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 +/- 1.0 g/dL [140 +/- 10 g/L]) was completely recovered before surgery (14.0 +/- 1.6 g/dL [140 +/- 16 g/L]) in the EPO group, while a decrease from 13.8 +/- 1.1 to 12.2 +/- 1.3 g per dL (138 +/- 11 to 122 +/- 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 +/- 29 micrograms per L in the EPO group and to 54 +/- 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: Preliminary results of a randomized, open-labeled, phase II trial

Purpose : To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. Methods and Materials : This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy ± chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the “treatment arm” receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO 4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. Results : Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1–6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. Conclusion : (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Pharmacokinetics of Intraperitoneal, Intravenous, and Subcutaneous Recombinant Human Erythropoietin in Patients on Continuous Ambulatory Peritoneal Dialysis

The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (IV), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following IV Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following IV Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the IV dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 ± 5.0 hours v 9.4 ± 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0.96; P = 0.0001). In addition, SC Epo was significantly more bioavailable than IP Epo (21.8% ± 15% v 11.4% ± 6.6%; P = 0.0001). Furthermore, 25.1% ± 11% of the IP dose was recovered in the 10-hour dialysate effluent. During the 96 hours of the study, 77.2% ± 14% of the SC dose was not absorbed. Compared with the IP dose, there was a larger percentage of unaccounted SC Epo dose (63.5% ± 13% v 77.2% ± 14%; P <0.05). In conclusion, despite its modest bioavailability, the pharmacokinetics of Epo following administration into a dry peritoneum suggest that the IP route may have potential clinical usefulness.

Subcutaneous Recombinant Human Erythropoietin in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis

We compared the effect of twice weekly subcutaneous recombinant human erythropoietin (SC rHuEPO) in two groups of patients treated with a starting dose of 80 U/kg body weight/week: group I, 7 hemodialysis (HD) patients; group II, 8 continuous ambulatory peritoneal dialysis (CAPD) patients. In a third group (group III) of 4 patients transferred from HD to CAPD with anemia previously corrected with intravenous (IV) rHuEPO, we studied the changes in the maintenance SC dose to maintain the same hemoglobin. In groups I and II the mean SC doses required to correct anemia and to maintain hemoglobin/hematocrit levels were similar; the mean time for the correction of anemia was significantly longer in HD patients (p = 0.032). In group III the maintenance SC rHuEPO does was reduced to more than 50% at 12 weeks of CAPD. Subcutaneous rHuEPO is effective in reversing anemia in HD and CAPD patients, but it takes longer to correct anemia in HD with the same initial SC rHuEPO low dose. CAPD patients need lower doses of SC rHuEPO than HD patients in IV therapy to maintain the same hemoglobin levels.

Effects of azathioprine on response of renal anaemia to subcutaneous recombinant human erythropoietin.

To determine the effect of concomitant azathioprine treatment on the response of patients with renal failure to treatment with subcutaneous recombinant human erythropoietin (r-HuEPO). Two groups of patients with renal failure not receiving haemodialysis were studied. One comprised seven patients receiving erythropoietin alone, the second consisted of nine patients who were also treated with azathioprine. The haematological changes were monitored, and the functional erythropoietic response was studied by two different ferrokinetic models. One analysed the initial, the other the extended plasma iron clearance. Studies were performed before r-HuEPO treatment on all 16 patients, and repeated on 11 of these when the target haemoglobin (10-11 g/dl) was achieved and stabilised. Total erythropoiesis was determined using both techniques. Analysis of the extended plasma iron clearance also permitted calculation of both effective and ineffective erythroid activity. The haematological response to r-HuEPO was the same for both patient groups. Measurement of total erythropoiesis by both ferrokinetic methods showed good correlation. For those receiving long term azathioprine, the percentage ineffective erythropoiesis was high compared with that of the other patients, and remained so for as long as they continued with azathioprine. For those uncomplicated by azathioprine treatment, r-HuEPO increased levels of both effective and ineffective erythropoiesis by the same degree. A substantial reduction in ineffective erythropoiesis was shown only by those patients who either discontinued or reduced their azathioprine once they started r-HuEPO treatment. Azathioprine increases ineffective erythropoiesis. In this study, the r-HuEPO dose was sufficient to overcome this effect and promoted effective erythropoiesis so that the anaemia lessened. Measurement of total erythropoiesis provided limited information on the functional changes involved, differentiation of effective from ineffective erythropoiesis being necessary to define the changes after azathioprine reduction or withdrawal.

Subcutaneous recombinant human erythropoietin for the treatment of anemia in myelodysplastic syndromes.

Recombinant human erythropoietin (rhEPO) was administered subcutaneously to 13 anemic (Hb < 10 g/dl) patients with myelodysplasia (MDS). rhEPO was given 3 times a week at doses of 75-250 U/kg body weight, over a maximum period of 24 weeks. Five patients (38%) showed a response to rhEPO treatment. rhEPO was well tolerated and without relevant side effects throughout the study. All responding patients had low but detectable pretreatment circulating erythroid progenitor cells (BFU-E) and the response to rhEPO was associated with a significant increase in BFU-E (p < 0.01); concentrations of serum transferrin receptor (TfR) also consistently rose in all responding patients. Baseline erythropoietin (EPO) concentrations did not significantly differ between responders and nonresponders, although 4 out of the 5 responders had relatively low levels of EPO. In conclusion, subcutaneous rhEPO administration appears to be an effective treatment of anemia in a substantial subset of patients with MDS. Relatively low baseline EPO concentrations, detectable pretreatment circulating BFU-E and an early increase in the serum concentrations of TfR seem to be criteria for predicting response to rhEPO in patients with MDS.

Effects of Subcutaneous Recombinant Human Erythropoietin in Patients on Continuous Ambulatory Peritoneal Dialysis

The use of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of renal anemia, but the dose regimens, the optimal frequency, and the effects on other target organs like the central nervous systems (CNS) are still under discussion. We designed a prospective, ongoing study with 10 stable continuous ambulatory peritoneal dialysis (CAPD) patients (6 males, 4 females; mean age 64.4 +/- 7.8 years), with a pretreatment hemoglobin (Hb) < 7.0 g% and requiring regular blood transfusions. Seven patients were treated with 4000 U rHuEPO once weekly (Eritrogen, Boehringer Mannheim), 2 patients received 4000 U every 5 and 8 days, and the last one 4000 U every 10 days. The target hematocrit was 33% and Hb 10.0 g%. The CNS activity was recorded as visual (VEP), brainstem (BAER), and somatosensory (SEP)-evoked potentials. The mean Hb concentration increased from 6.9 +/- 1.2 g% to 10.3 +/- 1.6 g% (p < 0.001) over 8 weeks. There were no significant changes in urea, creatinine, and potassium levels, and urine output. rHuEPO induced a decrease in latency of P100 VEP, in the four main components of BAER, and in the P27-N35 intertime of SEP. Parallel to the improvement of red cell indices, patients experienced a dramatic improvement in well-being. The subcutaneous administration of a single vial of rHuEPO is safe, convenient, and inexpensive in CAPD. The role of rHuEPO treatment in improving the electrophysiological brain function in uremic and anemic patients remains to be studied and may not necessarily be based on improved cerebral oxygenation.