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Early prediction of response to recombinant human erythropoietin in
patients with the anemia of renal failure by serum transferrin receptor and
fibrinogen
Y Beguin, M Loo, S R'Zik, B Sautois, F Lejeune, G Rorive and G Fillet
Department of Medicine, University of Liege, Belgium.
Recombinant human erythropoietin (rHuEpo) has been shown to be effective in
correcting the anemia of chronic renal failure, but the dose needed may be
variable. The reason for this variation is not known, but several factors
could be involved, such as iron deficiency, inflammation, aluminum
intoxication, hyperparathyroidism, blood losses, or marrow dysfunction.
Treatment with rHuEpo was given intravenously thrice weekly after
hemodialysis to 64 consecutive unselected patients with the anemia of
chronic renal failure. The starting dose was 50 U/kg/dose, which was
increased to 75 and 100 U/kg/dose if no response was observed after 1 and 2
months of treatment. After a minimum follow- up of 6 months, response was
evaluated as early (hematocrit [Hct] > or = 30% before 3 months) or late
(Hct > or = 30% after 3 months) response, or failure (target Hct not
attained). We examined the value of various laboratory parameters (baseline
values and early changes) as predictors of response to rHuEpo. The best
prediction by pretreatment parameters only was obtained with baseline serum
transferrin receptor (TfR) (< or > or = 3,500 ng/mL) and fibrinogen
(< or > or = 4 g/L): 100% response rate when both parameters were
low, versus only 29% when they were both high, and versus 67% when one was
low and the other high. When the 2-week TfR increment was greater than 20%,
the response rate was 96%. When TfR increment was less than 20%, the
response rate was 100% when baseline TfR and fibrinogen were low, 12% when
fibrinogen was elevated, and 62% when fibrinogen was low but baseline TfR
high. The predictive value of baseline TfR and fibrinogen and of the 2-week
increment of TfR was confirmed by life table analysis and stepwise
discriminant analysis. Major reasons for failure or late response were
identified and included subclinical inflammation, iron deficiency,
functional iron deficiency, marrow disorders, hemolysis, bleeding, and low
Epo dose. We conclude that response to rHuEpo can be predicted early by
pretreatment fibrinogen and TfR, together with early changes of TfR levels.
These prognostic factors illustrate the importance of the early
erythropoietic response, subclinical inflammation, and functional iron
deficiency. Early recognition of a low probability of response in a given
patient could help identify and correct specific causes of treatment
failure to hasten clinical improvement and avoid prolonged ineffective use
of an expensive medication.
Volume 82,
Issue 7,
pp. 2010-2016,
10/01/1993
Copyright © 1993 by The American Society of Hematology
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