Epoetin/Atra

Although both short-acting and long-acting erythropoietin-stimulating agents (ESAs) are used to treat anemia in patients undergoing hemodialysis, the relative effects on survival of these ESA types are unknown. In this nationwide, registry-based cohort study enrolling 194,698 patients on hemodialysis, the authors found that long-acting ESA users showed a 13% higher rate of death than short-acting ESA users (P<0.001) during the 2-year follow-up period. The difference in risk was pronounced among patients receiving high doses of ESA, for whom the adjusted 2-year number needed to harm for death was 30.8. Survival of long-acting ESA users who achieved more optimal hemoglobin levels was inferior to that of short-acting ESA users. Among patients on hemodialysis, long-acting ESA use might be associated with an increased rate of death compared with short-acting ESA use.

Despite the widespread use of erythropoietin-stimulating agents (ESAs) to treat anemia in patients undergoing hemodialysis, the relative mortality risks associated with use of different types of ESAs are unknown.

To compare the mortality risk associated with use of short-acting ESAs versus long-acting ESAs, we conducted a nationwide cohort study of 194,698 hemodialysis patients in Japan who received either a short-acting (epoetin α/β or epoetin κ) or a long-acting (darbepoetin or epoetin β pegol) ESA. Study outcomes were 2-year all-cause and cause-specific mortality. In addition to Cox proportional hazards models, we performed an instrumental variable analysis in which facility-level long-acting ESA prescription rates were taken as the instrumental variable.

During the 2-year follow-up period, 31,557 deaths occurred. In a multivariable Cox model, long-acting ESA users had a 13% higher rate of deaths compared with short-acting ESA users, a significant difference (P<0.001). Similar results were obtained in other analyses. This difference in risk was pronounced among patients receiving high doses of ESA (for whom the adjusted 2-year number needed to harm for death was 30.8). Long-acting ESA use was associated with an increased rate of death from cardiovascular diseases, infection, and malignancies. In the instrumental variable analysis, long-acting ESA users remained at a significantly higher risk of death. Compared with anemic (hemoglobin 9.0–9.9 g/dl) short-acting ESA users, long-acting ESA users who achieved more optimal hemoglobin levels (10.0–10.9 g/dl) showed a higher mortality rate.

Among patients undergoing hemodialysis, use of long-acting ESAs might be associated with a higher risk of death than use of short-acting ESAs.

Recombinant erythropoietin (rhEPO) has been misused for over two decades by athletes, mainly but not only in endurance sports. A direct rhEPO detection method in urine by isoelectric focusing (IEF) was introduced in 2000, but the emergence of third‐generation erythropoiesis‐stimulating agents and so‐called biosimilar rhEPOs, together with the sensitivity of human endogenous EPO (huEPO) pattern to enzymatic activities and its modification following short strenuous exercise, prompted the development of a complementary test based on SDS‐PAGE analysis. While Mircera and NESP are easily detected with the existing IEF and SDS‐PAGE methods, some samples containing both epoetin‐α/β and huEPO present profiles that are still difficult to interpret. As doping practices have moved to micro‐dosing, these mixed patterns are more frequently observed. We investigated the impact of enzymatic desialylation on the urinary and serum EPO profiles obtained by SDS‐PAGE with the aim of improving the separation of the bands in these mixed EPO populations. We observed that the removal with neuraminidase of the sialic acid moieties from the different EPOs studied reduced their apparent molecular weight (MW) and increased the migration distance between huEPO and rhEPO centroids, therefore eliminating the size overlaps between them and improving the detection of rhEPO. Copyright © 2013 John Wiley & Sons, Ltd.