Erythropoietin-Alpha Dosage Requirements in a Provincial Hemodialysis Population: Effect of Switching from Subcutaneous to Intravenous Administration

Abstract

Background: The purpose of this initiative was to compare erythropoietin-α doses in hemodialysis patients who changed from subcutaneous to intravenous administration. The Manitoba Renal Program switched routes due to concern about erythropoietin-associated pure red cell aplasia. Methods: We compared the erythropoie tin-α dosage requirements during subcutaneous administration (3 months pre-switch) and intravenous administration (months 4–6 post-switch). We also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent of patients receiving intravenous iron. The same erythropoietin-α regimen was initially used when patients were switched. Results: Of the 628 patients receiving erythropoietin-α, the data were complete for 400. The dose increased 26% (mean ± SD, 10,425 ± 7,330 vs. 13,125 ± 8,638 IU/week; p < 0.0001), despite similar hemoglobin, (mean ± SD, 11.5 ± 1.1g/dl (114.9 ± 11.2 g/l) vs. 11.3 ± 1.0 g/dl (113.5 ± 10.4 g/l); p = 0.0450) and iron parameters (Tsat 30.9%, ferritin 464 ng/ml (µg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (µg/l)). For the subgroup of 84 patients who maintained target hemoglobin (10–11 g/dl or 110–120 g/l) for both periods, the dose increased 26% (mean ± SD, 8,393 ± 6,242 vs. 10,589 ± 7,049 IU/week; p < 0.0001) without a change in hemoglobin, (mean ± SD, 11.5 ± 0.3 g/dl (115.2 ± 3.0 g/l) vs. 11.5 ± 0.3 g/dl (114.9 ± 3.3 g/l); p = 0.5789). When stratified by subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated the greatest increase (89%), and those with the highest dose (>20,000 IU/week) experienced no increase (–3%). Conclusion: Overall, erythropoietin-α doses increased by 26% when patients were converted from subcutaneous to intravenous administration.

Erythropoietin modulates the neural control of hypoxic ventilation

“…Therefore, oxygen must be continuously supplied to settle the oxygen-dependent enzymatic reactions [50]. As a result, mammals need to be equipped with more than one mechanism to respond to the oxygen reduction in arterial blood.…”

Administration of the same dose of epoetin-beta intravenously and subcutaneously to patients with renal anaemia

“…These differences may account for the different results between the studies. In other observational studies [18][19][20][21][22][23], a small prospective sequential study [24] and a retrospective survey [12], s.c. EPO was converted to an i.v. formulation, demanding 11-35% higher EPO doses.…”

“…Three of the studies were smaller, with 41-86 patients [20,21,24]. In some of the studies the patients were iron replete [18][19][20][21] or nearly all iron replete [12,24], but in the study by Pussell and Walker, of 2214 patients [22], 43% were not iron replete, and in the study by McFarlane et al [23] a considerable proportion, too, was not iron replete, since median ferritin was 91 (48-181) mg/l at baseline and did not change during the study.…”

“…First, the dosing interval of i.v. EPO was not predetermined in the studies [19][20][21][22], but adjusted by the treating nephrologist after the switch from s.c. to i.v., based on individual response. In i.v.…”

The Efficacy of Intravenous versus Subcutaneous Recombinant Erythropoietin in Obese African-African Patients in a Southeast U.S. Dialysis Cohort

“…The most common route of rhuEPO administration in United States is the intravenous (IV) route, in keeping with KDOQI guidelines favoring IV administration for patient convenience 1 . However, IV conversion has been associated with increased rhuEPO and intravenous iron requirements [3] and up to 30% less total dosing of rhuEPO might be required to achieve identical hemoglobin (Hgb) goals via subcutaneous (SC) route [4,5]. One theoretical criticism of SC rhuEPO dosing is the reduced or variable efficacy in obese patients due to decreased bioavailability.…”