The effect of i.v. iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period
Ds. Silverberg et al., The effect of i.v. iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period, CLIN NEPHR, 55(3), 2001, pp. 212-219
Background: It is now more and more evident that anemia of predialysis chro
nic renal failure (CR-F) should be actively treated, since long-standing an
emia may cause irremediable damage to the heart. The most common form of tr
eatment of this anemia is subcutaneous erythropoietin (EPO). iron (Fe) defi
ciency can also contribute to anemia in predialysis CRF, and intravenous ir
on (i.v. Fe) can frequently improve it. It is possible, therefore, that the
combination of EPO and i.v. Fe may have an additive effect, and cause a ra
pid improvement in anemia with relatively small doses of EPO. Purpose: The
purpose of this study was an initial study: to assess the ability of a comb
ination of low-dose EPO and i.v. Fe, given weekly for 5 doses, to correct t
he anemia of predialysis CRF patients compared to the use of i.v. Fe alone
in a randomized study. In the follow-up study: to assess the ability of the
maintenance of adequate iron stores for one year to achieve and maintain t
he target Het of 35% with the minimum dose of EPO. Initial study: Method: N
inety predialysis CRF patients creatinine clearance 10 - 40 ml/min/1.73 m(2
) received either: Group A (45 patients): 200 mg i.v. Fe as Fe sucrose (Ven
ofer, Vifor Int.) once per week for 5 doses in combination with 2000 intern
ational units (IU) EPO (Eprex, Cilag-Janssen), subcutaneously given simulta
neously also for 5 doses. Group B (45 patients): the same dose of i.v. Fe a
s in Group A but without EPO. Results: The mean increase in hematocrit (Het
) and hemoglobin (Hb) by one week after the last dose was greater in group
A, 4.54 +/- 2.64% (p < 0.01) and 1.37 +/- 0.84 g% (p < 0.01), respectively,
than in Group B, 2.74 +/- 2.72% (p < 0.05) and 0.91 +/- 0.78 g% (p < 0.05)
, respectively. 80% of those in Group A had an increase in Hct of 3 vol% or
more compared to 48.9% in Group B (p < 0.01). 40% of those in Group A reac
hed the target Hct of 35% compared to 28.9% in Group B (p > 0.05). Follow-u
p study: During a 12-month follow-up period, enough i.v. iron was given to
maintain the Hct at 35%, while keeping the serum ferritin at < 400 ug/l and
% Fe Sat at < 40%. If the i.v. Fe alone was not capable of maintaining the
target Hct, EPO was given in increasing doses. Eighteen patients required
dialysis. Of the 72 patients who did not require dialysis, 24 (33.3%) maint
ained the target Hct with i.v. Fe alone, without EPO. All the remaining 48
patients (66.7%) continued to receive EPO in addition to the i.v. Fe, and 4
7 achieved and maintained the target Hct with a mean EPO dose of 2979 +/- 1
326 IU/week. Conclusion: The combination of low-dose EPO and i.v. Fe had a
rapid and additive effect on the correction of anemia in CRF predialysis pa
tients. Maintaining adequate iron stores with i.v. Fe during a subsequent m
aintenance phase allowed the target Hct of 35% to be reached and maintained
with low-dose EPO in two-thirds of the predialysis patients and with no EP
O at all in one-third.