Anemia Treatments

Blood Transfusion

Early on, anemia was primarily managed by blood transfusions given on a regular basis every 2 to 3 weeks (Fricke, 2006). These increased the patient's risk of infection, including transmission of diseases, such as hepatitis B and C, and HIV, since testing of blood for these substances was not fully developed at that time. Transfusion over time can also suppress endogenous erythropoiesis and lead to iron overload (Schmidt & Besarab, 2008). Blood transfusions can lead to the development of sensitivities to major histocompatibility antigens and lead to sensitization of potential transplant recipients (Schmidt & Besarab, 2008).

Androgenic-Anabolic Steroids

Investigations in the 1970s and 1980s indicated that the administration of androgens resulted in the stimulation of erythropoiesis, with favorable effects on anemia in patients on hemodialysis. Initially, this effect was thought to be due to an increase in EPO production, but subsequent studies implicated other mechanisms of action (Navarro, 2003). Some of the compounds used included nandrolone decanoate (100 mg administered intramuscularly [IM]/week) for women and testenterone (200 mg IM/week) for men. Side effects include acne, hirsutism, and hepatotoxicity, and often necessitated changes in doses or discontinuation of the medication (Jacobsson & McNatt, 1986). The side effect profile, safety and efficacy concerns about these medications, and the development of recombinant human erythropoietin led to decreased use of anabolic steroids.

Development of Recombinant Human Erythropoietin

anemia treatment
The gene for recombinant human erythroietin was identified in 1983, and two years later, clinical trials were started to evaluate its safety and efficacy. In 1989, recombinant human erythropoietin (Epoetin alfa) was approved for treatment of anemia associated with CKD in the United States and Europe (Fricke, 2006). Treatment with Epoetin alfa has revolutionized the management of patients with CKD, and has resulted in raised hemoglobin levels and decreased use of blood transfusions. Studies have confirmed its beneficial effects, including decrease of symptoms related to anemia and improved quality of life and functional status. Subsequent studies have found improvements in left ventricular hypertrophy, cognitive function, exercise and activity levels, and hospitalization and mortality rates (Tsai & Berns, 2008).

Dosing of ESAs

When Epoetin alfa was approved for use in 1989, more than 900/0 of patients had a hemoglobin (Hb) level less than 11 g/dL, so it is not surprising that the initial focus was to increase Hb levels and decrease the percentage of patients below 11 g/dL (Breiterman-White, 2007). However, the goals of therapy and the dosing patterns have been influenced over the years by reimbursement policies, package labeling, results from clinical studies, and the development of clinical practice guidelines (Tsai & Berns, 2008).

Influence of Clinical Practice Guidelines

In 1997, the NKF developed clinical practice guidelines concerning the use of Epoetin alfa in patients on hemodialysis--the Kidney Dialysis Outcomes Quality Initiative (DOQI) (NKF, 1997). The guidelines were revised in 2001 with recommendations concerning patients with CKD. The importance of achieving a minimum Hb of 11 g/dL was stressed and developed into a quality indicator of care. Revisions to these guidelines were released in 2006 and 2007, and they recommend a target Hb of 11.0 g/dL for the lower limit and 13.0 g/dL for the upper limit (NKF, 2006).