Anemia is highly prevalent among ESRD patients, as a result of diminished erythropoietin production. Erythropoietin stimulating agents (ESAs) have been used successfully to address inadequate renal erythropoietin production in patients with chronic kidney disease (CKD). However, the safety of normal target levels for hemoglobin (Hb) production remains unclear. In addition, the effects of different Hb targets on blood transfusion requirements have not been well characterized. It is important to understand this relationship for clinical decision-making, as well as because of potential transfusion-related infection deleterious immunomodulatory effects in patients whom renal transplantation is a consideration. Therefore, Foley et al conducted a study to test the hypothesis that normal Hb targets can reduce transfusion rates compared with conventional targets.

The study population was comprised of 596 incident hemodialysis patients without symptomatic cardiac disease. This was a randomized, controlled trial comparing normal Hb targets to partial correction of anemia, when treating with epoetin alfa. Patients were randomly assigned to Hb target levels of either 9.5-11.5 g/dL (low target) or 13.5-14.5 g/dL (high target). Patients and physicians were masked to treatment assignment, but doctors had access to ongoing Hb values. The study took place in 95 treatment centers in 10 countries between February 2000 and June 2001.

Adverse events occurred within 4 weeks before the first transfusion and were diverse and similar across both study groups. There were 20 deaths in low target subjects and 13 deaths in high target subjects (not significantly different). Blood cell transfusions differed significantly according to the study group, with 9.1% (high target) and 19.3% (low target) receiving blood transfusions. Hemoglobin levels measured immediately preceding transfusions were similar in both groups. Other multivariate associations of transfusion included baseline Hb level, epoetin dose, transferrin saturation, sex, dialysis duration, body mass index, European or Canadian study site, dialysis vascular access, and serum albumin level.

The authors concluded that based on the data, targeting normal Hb levels can lower blood transfusion requirements in incident hemodialysis patients without symptomatic cardiac disease, in which the mortality rates are low.

Foley RN, Curtis BM, Parfrey PS. Hemoglobin targets and blood transfusions in hemodialysis patients without symptomatic cardiac disease receiving erythropoietin therapy. Clin J Am Soc Nephrol. 2008 Nov;3(6):1669-75.

NAAC Expert Commentary
Anemia management is a near universal clinical issue of importance for patients with CKD and receiving hemodialysis (HD). The availability of safe and effective ESAs and intravenous iron preparations has made it possible to manipulate the Hb level and treat the complication of anemia very effectively, precluding the need for repeated blood transfusions in most patients. What remains somewhat controversial is the optimal target Hb level for ESA-treated patients, primarily for reasons of safety – a controversy that has prompted slightly different treatment recommendations from the U.S. Food and Drug Administration (FDA) and the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI).^1,2

In this study, Foley et al evaluated the impact of a “high” and “low” target Hb level on cardiac morphology in adult patients on HD without cardiac disease, while also investigating the on-study transfusion history of these patients. The study revealed that the (1) proportion of patients transfused per year and (2) per patient transfusion rate were significantly lower in those patients targeted to the higher Hb level, with no substantial difference in the incidence of adverse events. These findings are important as they provide observational data supporting a possible strategy to decrease the risk of transfusion related complications.

The study had a number of limitations, though, which included: (1) treating physicians having knowledge of the Hb levels (2) the lack of information on the indications for transfusion, and (3) the inability to generalize the study results to those patients with cardiac disease. However, further data on this subject is clearly warranted in our quest to individualize therapy in this era of healthcare reform in the most cost effective manner possible.

References

1. U.S. Food and Drug Administration. Communication About an Ongoing Safety Review Erythropoiesis-Stimulating Agents (ESAs) Epoetin alfa (marketed as Procrit, Epogen) Darbepoetin alfa (marketed as Aranesp). Link. Accessed: March 2008.
2. National Kidney Foundation. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007 Sep;50(3):471-530. Link.

Last Updated: August 13, 2009