HDCN Article Review/Hyperlink

Parker KP, Mitch WE, Stivelman JC, Macon EJ, Bailey JL, Sands JM

Safety and efficacy of low-dose subcutaneous erythropoietin in dialysis patients

J Am Soc Nephrol (Feb) 8:288-293 1997

The subcutaneous administration of recombinant human erythropoietin (EPO) may be a more effective route of administration than intravenous dosing. Two factors would explain this; 1) When administered IV, EPO receptors on erythropoietic tissue may become saturated, whereas SQ dosing allows for slower uptake from tissue, no over saturation and therefore greater overall stimulation of EPO receptors; 2) The rapid (superphysiologic) burst in erythropoiesis created by IV dosing causes a demand on iron supplies that is often greater than iron stores can satisfy, causing functional iron deficiency- SQ dosing allows more efficient use of iron. Studies of SQ EPO have tended to confirm the greater efficacy of SQ dosing, however have been criticized because of the short duration of published trials. This study by Parker et al is the first long term study comparing IV to SQ dosing.

44 hemodialysis patients were treated for 6 months with standard IV dosing of EPO, followed by 10 months of SQ dosing (1/3 the entire IV dose given once weekly SQ), and then a 6 month crossover back to IV dosing. A group of concurrent controls (this was not a randomized trial) were used for comparison. In the experimental group, there was no change in mean Hct from the initial IV to the SQ phase, and again in the IV phase. In contrast, the mean EPO dose was 103 +/- 4 u/kg/w in the IV phase, decreased to 31 +/- 1 u/kg/w in the SQ phase (p<0.05), and increased again to 115 +/- 5 u/kg/w when patients were switched back to IV EPO. In the control group, the Hct was stable over time, and the EPO dose was the not significantly different than the experimental group, except when the experimental patients were in the SQ dosing phase (during which time the controls had significantly higher EPO doses).

This study powerfully demonstrates the superior efficacy of SQ dosing of EPO over the long term. The design of the study could have been improved by having randomized patients to either IV or SQ dosing. Nonetheless, the crossover design in conjunction with the concurrent controls provided powerful and convincing results. As with most studies of medical therapies, measures of patient satisfaction were lacking, which would have added to the importance of this study. In addition, it would be of interest to analyze the heterogeneity of response to SQ dosing- do all patients have as powerful a response?

Comment: In summary, this study adds to a growing body of knowledge, and provides the first long term evidence of the superiority of SQ compared to IV EPO. I would recommend SQ dosing in all hemodialysis patients willing to accept the injections. (Stephen Fishbane, M.D., Winthrop University Hospital, Mineola, NY)