Once-weekly epoetin alfa for treating the anemia of chronic kidney disease.

BACKGROUND AND AIM: Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population. METHODS: This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) < or = 10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events. RESULTS: 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of > or = 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly epoetin alfa was well tolerated, similar to that reported with three times-weekly dosing. CONCLUSION: Once-weekly epoetin alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

Androgens in the anaemia of chronic renal failure.

Plasma levels of testosterone-like substances (TLS) were depressed in seven patients with chronic renal failure. Intramuscular testosterone (as Sustanon 250 once a week) elevated plasma TLS levels to above normal throughout the week with an initial high peak. Sublingual testosterone produced a high but brief peak in TLS. Results were similar in renal failure patients and normal controls. A controlled trial of weekly Sustanon 250 in 24 regular dialysis patients produced a significant increase in haemoglobin from 6.8 to 8.2 g/dl. Side effects were mainly mild and acceptable but one patient developed priapism and another a large haematoma. The discriminate use of androgens is recommended for anaemic male patients on regular haemodialysis.

Response to parenteral iron with and without androgen therapy in patients undergoing regular haemodialysis.

The effects of intravenous iron, with and without androgens, was studied in a group of 39 patients treated by regular haemodialysis, almost all of whom had normal serum iron concentrations. Intravenous iron 1-2 g every 4 months produced a significant rise in haemoglobin from 6.3 to 7.9 g/dl in 17 female patients with their kidneys in situ (p less than 0.001). In a group of 13 male subjects intravenous iron plus testosterone produced a similar rise in haemoglobin from 6.9 to 8.6 g/dl (p less than 0.001). Nine nephrectomised patients showed no significant response to iron and androgens. There were no fatalities and no serious side effects in 500 courses of intravenous iron.

Effects and complications of high efficiency dialysis.

Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.