The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Swedish Study Group.

BACKGROUND: Anaemia in haemodialysis patients can be effectively treated with erythropoietin. We investigated whether subcutaneous (SC) epoetin ss administered once weekly was as effective as the same weekly dosage given in two to three divided doses. METHODS: One hundred and fifty-eight patients (delivered Kt/V >1.0, where K=dialyser-renal urea clearance, t=dialysis time and V=filtration volume, obtained by urea kinetic modelling) were randomized to treatment with SC epoetin beta either once weekly (n=118), or to their original dosage two or three times weekly (control group, n=40) for 24 weeks. All patients received intravenous iron supplementation when necessary. RESULTS: Eight-eight patients in the once weekly group and 30 patients in the control group were treated for at least 16 weeks and are included in the analysis. Stable haemoglobin levels were maintained without epoetin dose increases in 73% of patients in both groups. Mean haemoglobin levels at randomization and after 16 and 24 weeks were 11.4, 11.1 and 11.1 g/dl, respectively, in the once weekly group compared with 11.2, 11.3 and 11.2 g/dl, respectively, in the control group. The mean weekly epoetin beta dosages at randomization and after 16 and 24 weeks were 102, 103 and 106 IU/kg bodyweight, respectively, in the once weekly group compared with 109, 109 and 115 IU/kg bodyweight, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin beta dosages at week 24. CONCLUSIONS: Once weekly SC administration of epoetin beta is as safe and effective in maintaining haemoglobin levels in stable haemodialysis patients as two or three times weekly administration of the same total dose. By using the once weekly regimen, patients can avoid up to 104 injections per year. This would reduce clinic time for patients who do not self administer, and may also encourage self-administration and improve overall compliance.

Breast-feeding during treatment with cyclosporine.

BACKGROUND: Mothers treated with cyclosporine (CsA) have previously not been allowed to breast-feed due to the reported accumulation of the drug in breast milk. The purpose of this study was to evaluate the consequences of allowing breast-feeding. METHODS: Seven infants were breast-fed by mothers who had undergone kidney transplantation alone (n=5) or simultaneous kidney and pancreas transplants (n=2). In addition to CsA, all mothers received prednisolone at 5-7.5 mg/day and six mothers received azathioprine at 50-100 mg. CsA concentration was measured in the whole blood of mothers and babies and in breast milk. Serum creatinine was measured in babies 1 week after birth and after 4-12 months of breast-feeding. RESULTS: Blood CsA levels ranged from 55 to 130 ng/ml in mothers (12-hr trough), 50 to 227 ng/ml in breast milk (mean for each woman), and was below the detection limit of 30 ng/ml in all infants. Breast milk concentration ranged from 87 to 440 ng/ml in 16 samples obtained at various time points from one mother. Infants' serum creatinine ranged from 25 to 54 micromol/L at 1 week after birth and 23-52 micromol/L after breast-feeding. All babies thrived. CONCLUSIONS: Breast-fed infants of mothers treated with CsA received less than 300 microg per day of CsA and absorbed undetectable amounts. There were no demonstrable nephrotoxic effects or other side effects. Thus, women with kidney transplants could be allowed to breast-feed.

Subcutaneous epoetin beta in renal anemia: an open multicenter dose titration study of patients on continuous peritoneal dialysis.

OBJECTIVE: To establish dose requirements (target hemoglobin > 100 g/L) and safety of subcutaneously administered epoetin beta. DESIGN: Open multicenter study. PATIENTS: Forty-five anemic patients (21 female, 24 male; mean age 55 years; range 20-79 years) who had been on continuous peritoneal dialysis for 1-157 months (mean 24 months). Thirty patients required blood transfusions during the year prior to the study. Mean hemoglobin concentration pretreatment was 75 g/L (range 57-89 g/L). INTERVENTION: After a pretreatment period of two weeks, 60 IU kg-1 week-1 divided into three weekly doses of epoetin beta was administered subcutaneously. The dose was increased by 60 IU kg-1 week-1 after ten weeks, and when necessary, every fourth week in patients with hemoglobin levels below 100 g/L. MAIN OUTCOME MEASURES: Hemoglobin concentration. Analysis of factors affecting the response to epoetin beta. Safety of epoetin beta. RESULTS: Thirty-eight of the 45 patients completed six months and 21 patients completed one year in the study. Twenty-six patients reached hemoglobin 100 g/L within six months and 8 patients did later on. The mean hemoglobin concentration after three months was 93 g/L (range 64-144 g/L) and after six months was 99 g/L (range 59-130 g/L; mean epoetin beta dose 122 IU kg-1 week-1). During the second six-month period of the study, hemoglobin levels were stable in most patients. After one year, the mean hemoglobin was 110 g/L (range 84-153 g/L) and the mean epoetin beta dose was 107 IU kg-1 week-1. Prolonged correction time and impaired response to epoetin were observed in patients with infections or hemorrhages and in patients with low hemoglobin concentration before starting epoetin treatment. Iron deficiency was controlled by iron supplementation, either orally or, in 10 patients, intravenously. Increased blood pressure, requiring intensified antihypertensive treatment, was observed in 13 patients. CONCLUSIONS: Continuous peritoneal dialysis patients with moderate anemia (Hb 75-90 g/L) and without complicating disorders can be managed with subcutaneous doses of epoetin < 120 IU kg-1 week-1. The epoetin beta dose should be adjusted after the first month of treatment since most patients required higher doses than the initial 60 IU kg-1 week-1.