Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients

N Engl J Med. 1998 Aug 27;339(9):578-83. doi: 10.1056/NEJM199808273390902.


Background: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level.

Methods: In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration.

Results: For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild.

Conclusions: In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Anemia / blood
  • Anemia / drug therapy*
  • Dose-Response Relationship, Drug
  • Epoetin Alfa
  • Erythropoietin / administration & dosage*
  • Female
  • Hematinics / administration & dosage*
  • Hematocrit
  • Humans
  • Infusions, Intravenous / adverse effects
  • Injections, Subcutaneous / adverse effects
  • Iron / therapeutic use
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Pain / etiology
  • Recombinant Proteins
  • Renal Dialysis*


  • Hematinics
  • Recombinant Proteins
  • Erythropoietin
  • Epoetin Alfa
  • Iron