Subcutaneous recombinant human erythropoietin decreased anemia in predialysis patients with chronic renal failure
ACP J Club. 1991 Jan-Feb;114:11. doi:10.7326/ACPJC-1991-114-1-011
Watson AJ, Gimenez LF, Cotton S, Walser M, Spivak JL. Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin. Am J Med. 1990;89:432-5. [PubMed ID: 2220877]
To assess the effectiveness of subcutaneous recombinant human erythropoietin (r-HuEPO) in treating anemia in predialysis patients with chronic renal failure.
Randomized, double-blind, placebo-controlled trial lasting 12 weeks. After the initial 12 weeks, all patients received r-HuEPO and were followed for 40 to 52 weeks.
Outpatient clinical research center at a medical school in the United States.
6 men and 5 women (ages 43 to 79 y) were included. All had predialysis chronic renal failure from various causes. No information was given as to the pool of patients from which these 11 were chosen.
Patients were randomized to receive subcutaneous injections of r-HuEPO (100 U/kg body weight) or placebo 3 times per week for 12 weeks or until a hematocrit of 0.38 was reached. After 12 weeks, both groups received r-HuEPO on long term maintenance; the dose was increased for nonresponders to 150 U/kg body weight and decreased to a once-weekly maintenance dose when the target hematocrit was reached. Thereafter, patients administered injections themselves and were seen monthly.
Main outcome measure
Hematocrit values were measured at baseline and at 12 and 24 weeks.
At baseline the mean hematocrit was 0.29 (95% CI 0.25 to 0.33) for patients receiving r-HuEPO and 0.28 (CI 0.24 to 0.32) for the placebo group. At week 12, the mean hematocrit for the r-HuEPO group had risen compared with baseline values and with values of the placebo group (r-HuEPO, 0.35 [CI 0.31 to 0.39; placebo, 0.26 [CI 0.22 to 0.30], P < 0.001). At week 24 (when both groups had been receiving r-HuEPO for 12 weeks), the mean hematocrits did not differ between groups. The mean hematocrit for the placebo group at week 24 was higher than at week 12 and at baseline (P < 0.001). No significant differences existed between the groups for mean blood pressure, creatinine clearance, or other possible adverse effects of therapy. The power of the study to detect important worsening of blood pressure control or renal function was not provided.
In predialysis patients, subcutaneous recombinant human erythropoietin increased the hematocrit without the disadvantages of other methods such as intravenous combined human erythropoietin or blood transfusion.
Sources of funding: Ortho Pharmaceuticals Inc. and the National Institutes of Health.
Address for article reprint: Dr. A. J. Watson, The Johns Hopkins School of Medicine, 1830 East Monument Street, Room 8020, Baltimore, MD 21205, USA.
Recombinant human erythropoietin (EPO), given intravenously, or even better, subcutaneously, represents a major advance in treating patients with end-stage renal failure. It has been studied most frequently in patients on hemodialysis and has been shown to increase hemoglobin levels, improve quality of life, and permit avoidance of transfusion with its concomitant risk of infection, iron overload, and sensitization (1). The major side effects of the medication have been hypertension and flu-like symptoms.
Subcutaneous EPO can be self-administered and may require a lower dose than intravenous EPO (unfortunately, the mean maintenance dose of erythropoietin in this study was not indicated). The authors found no difference in hypertension between the 2 groups, and no unexpected side effects were reported. There has been concern that the increase in hematocrit in predialysis patients treated with EPO may be associated with acceleration of renal failure. Other studies have found no change in the glomerular filtration rate with EPO therapy (2), but Watson and coworkers discontinued therapy with EPO because of a suspicion of accelerated renal failure in 2 of the 5 patients in whom the glomerular filtration rate was measured. They did not indicate why glomerular filtration rates were reported for only 5 of the 11 patients. A larger randomized controlled trial with a longer follow-up is needed to determine whether the increase in hematocrit associated with EPO therapy accelerates renal failure.
Andreas Laupacis, MD
University HospitalLondon, Ontario, Canada