Ferric Gluconate Reduces Epoetin Requirements in Hemodialysis Patients with Elevated Ferritin

Abstract

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) Յ25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of Ϫ7527 Ϯ 18,021 IU/wk, P ϭ 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 Ϯ 19,987 IU/wk, P ϭ 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P ϭ 0.062, P Ͻ 0.001, and P ϭ 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio ϭ 1.73, P ϭ 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Evaluation of the Change in Hemoglobin Values after the Administration of Intravenous Iron Therapy on Chronic Hemodialysis Patients with Anemia and Elevated Ferritin Levels

“…This supports the use of IV iron without added risk of iron overload. It was expected that increased IV iron use in this population would result in reduced epoetin doses as the finding reported with Kapoian and colleagues [8]. However, average weekly epoetin doses decreased in the ferric gluconate group but not in the iron sucrose and iron dextran therapy groups.…”

“…Consequently, DRIVE-II was extended for another 6 weeks to observe the effects of a 1-gram course of ferric gluconate over a total duration of 12 weeks. The authors showed that patients receiving ferric gluconate required less epoetin and had fewer serious adverse events [8]. Pizzi, et al examined the economic impact of DRIVE and DRIVE-II and concluded there were cost saving benefits for patients with high ferritin and low saturation levels treated with ferric gluconate and epoetin combination therapy compared to epoetin alone [9].…”

Combined High Serum Ferritin and Low Iron Saturation in Hemodialysis Patients

“…Hence, moderately high levels of serum ferritin should not be assumed to indicate adequate to high iron stores, and patients with ferritin levels Ͼ500 ng/ml, especially if combined with a low ISAT of Ͻ25%, should not be automatically labeled as iron overload and, hence, deprived of iron supplementation (11,45). Indeed, in a recent randomized clinical trials to assess response to intravenous iron in anemic MHD patients with this seeming paradoxical constellation, administration of 1000 mg of intravenous iron gluconate led to significantly improved anemia and responsiveness to ESA (12,46). Therefore, even though inflammation, especially in the paradoxical high-ferritin/low-ISAT group, may lead to ESA hyporesponsiveness (4), administration of IV iron gluconate still appears to improve anemia management (12,46).…”

“…Indeed, in a recent randomized clinical trials to assess response to intravenous iron in anemic MHD patients with this seeming paradoxical constellation, administration of 1000 mg of intravenous iron gluconate led to significantly improved anemia and responsiveness to ESA (12,46). Therefore, even though inflammation, especially in the paradoxical high-ferritin/low-ISAT group, may lead to ESA hyporesponsiveness (4), administration of IV iron gluconate still appears to improve anemia management (12,46). This response may be the result of the effect of intravenous iron on decreasing such inflammatory cytokines as TNF-alpha observed in a recent clinical trial (47).…”

ESA treatment in dialysis patients: Where do we go now?

“…14 Further, in patients who are ESA resistant and on high doses of ESA, treatment with intravenous iron reduces epoetin requirements. 15 Additionally, consideration should be given to removing the allograft as it is the likeliest source of infl ammation in this patient.…”