Wallner, M., Stummvoll, H.-K., Robl, B., Seiringer, E., Neyer, U., Waller, I., Wiesholzer, M., Pronai, W., Grobner, T., Graf, H., and Kramar, R.
Objective: Due to the sudden increase of pure red cell aplasia in hemodialysis patients observed predominantly in Europe between 1998 and 2002, the route of erythropoietin (EPO) administration in hemodialysis (HD) patients had been switched from s.c. to i.v. in many HD units in Austria. In accordance with the bulk of published papers providing evidence of significant EPO dose reduction with s.c. use, and the US K-DOQI guidelines as well as the European Best Practice Guidelines concerning the preferable route of EPO administration, a significant rise in EPO requirement had to be expected, if the hemoglobin of the patients were to remain stable. Methods: Nine HD units in Austria participated in this nonrandomized cross-over study. All patients (n = 349) on s.c. EPO therapy for at least 6 months were switched to i.v. EPO administration and observed for another 6 months. Hemoglobin values and EPO doses were recorded weekly, ferritin, transferrin saturation, and CRP were done monthly. The study population consisted of 203 male (58%) and 146 female (42%) patients, mean age 62.6 ±redren; 13.9 years (range 21-90), mean height 167.5 ± 8.5 cm (range 143-193), mean body weight 70.4 ± 14.9 kg (range 37-149), duration of dialysis 65.6 ± 58.6 months (range 1-339). Primary cause of renal failure was diabetes in 23%, glomerulonephritis in 24%, hypertension and renovacular disease in 16%, pyelonephritis in 10%, polycystic kidney disease in 9%, miscellaneous in 13%, and unknown in 5%. Epoetin alpha was used in 70% (group α), epoetin beta in 14% (group β), and darbepoetin alpha (group δ) in 16% of patients. To obtain comparable results in EPO use, the dose of darbepoetin alpha (in µg) was multiplied by 200, as indicated by the manufacturer. The dosing of EPO and iron substitution was left to the discretion of the participating centers. Target level of hemoglobin was ≥11 g/dl, according to the above mentioned guidelines. Results: The average weekly dose of EPO per kg of body weight (all three groups) remained stable during the s.c. and the i.v. study phase (mean [±SD], 131.0 ± 102 vs. 130.9 ± 95 IU; p ± 0.47); in particular, group α 124.0 ± 104 vs. 125.3 ± 97 IU, p = 0.34; group β 159.3 ± 79 vs. 167.0 ± 79 IU, p = 0.51; group δ 128.6 ± 100 vs. 126.2 ± 100 IU, p = 0.72). A small but statistically significant increase of the hemoglobin level was observed between the s.c. and i.v. phase (mean [±SD], 11.7 ± 1.01 vs. 11.9 ± 0.96 g/dl; p ≤ 0.001); this was due exclusively to a rise of hemoglobin in group β (11.5 ± 0.8 vs. 11.9 ± 0.7 g/dl) and group δ (11.7 ± 0.9 vs. 12.1 ± 0.8 g/dl), whereas hemoglobin in group α remained stable (11.7 ± 1.01 vs. 11.8 ± 1.02 g/dl). Most of the patients were iron-replete, as documented by a mean transferrin saturation ≥ 21%, and not differing significantly between the three groups (group α 23.3 ± 8.4%, group β 21.9 ± 4.5%, group δ 23.3 ± 5.9%). However, the ferritin level in group δ was significantly higher (328 ± 180 ng/ml) than in group α and group β (257 ± 214 ng/ml, and 236 ± 125 ng/ml, respectively). In general, transferrin saturation and ferritin levels tended to be higher during the i.v. phase as compared to the s.c. phase. Conclusions: Switching from subcutaneous to intravenous administration of EPO, while maintaining the hemoglobin in a stable target range, did not increase the average weekly dose of EPO during an observation period of twelve months in this unselected population of iron replete, chronic HD patients.… [ABSTRACT FROM AUTHOR]