Q:  Monitoring hemoglobin levels and adjusting doses for erythropoietin stimulating agents (ESAs) in patients with anemia secondary to CKD is time consuming, labor intensive, and multi-factorial in nature. In our CKD clinic, results are generally poor with many missed injections. Concern about reimbursement adds to the complexity. Any suggestions for managing this clinical challenge?
 
A: Anemia is one factor in the CKD population that remains undertreated and has been linked to poor patient outcomes, including increased mortality (Obrador, Ruthazer, Arara, Kausz & Pereira, 1999). Erythropoietin stimulating agents (ESAs) represent one of the miracle medications used to treat the anemia associated with CKD. This class of medication has provided enormous benefits for those who suffer from illness and treatments that cause anemia, resulting in fatigue. However, ESAs also represent one of the most costly medications delivered in health care systems across the nation. Medicare spending on ESAs in the population of patients on dialysis rose to $1.8 billion in 2004, an increase of 17% from 2003 (USRDS, 2006). The cost associated with ESAs warrants careful patient monitoring and medication management.
At one Midwest integrated delivery system in Wisconsin, an investigation into the use of ESAs for the treatment of anemia revealed deficits in achieving evidence-based practice and results. Data in 2004 from four hospitals in this system demonstrated that cost of ESA administration was over $ 2 million dollars. Sixty six percent (66%) of these ESAs were given in the outpatient setting, often to those with anemia related to CKD. Additionally, care was time consuming for patients and staff, protocols were inconsistent, and clinical outcomes unclear. It was clear that quality outcomes, clinical efficiency, and cost reduction could be achieved through the use of a different, innovative model for medication delivery. In 2005, anemia management clinics were created in the outpatient departments, primarily for those with CKD.
Currently, in each of the hospital outpatient anemia management clinics, patients come in to be tested and receive their ESA injections every 2 to 4 weeks. The process is completely managed by expert outpatient nurses and pharmacists who are delighted with this practice. Treatment times for patients have dropped from 1-2 hours down to, at times, only 15 minutes. Patients and families no longer have to remain in the outpatient departments for hours to obtain lab results and ESA administration orders. Clinical outcomes for each patient were tracked, and the administration of this expensive drug at times when it cannot be physiologically used by the patient have been eliminated. Medication costs have decreased while the treatment goals of maintaining hemoglobin levels between 11.0 and 12.0 g/dL have been closely monitored (see Figure 1).

• Evidenced based standard order sets, which capture information pertinent for Medicare (CMS) approval / payments and provide a standardized protocol for ESA administration (refer to the Anemia Management in CKD Protocol in Figure 2).
• Approved protocols for ESA administration in tandem with IV iron therapy based on every 3-month iron studies (refer to the Iron Management Protocol in Figure 3).

• Flow sheets, which double as the medication record and communication tool, are sent to the physician’s office after each patient visit.
• Point of care testing using the Hemocue (hemoglobin analyzer) allows for close monitoring and appropriate dose adjustments of the ESA medication. This devise uses a capillary finger sample of blood to provide a hemoglobin result within a few minutes, that if done correctly, is within .5 g/dL of a venous sample. There is a technique to be mastered in using the Hemocue. In fact, technique has the most decisive effect on results in this point of care testing (Nygaard-Pedersen, 1997). Representatives for the Hemocue as well as skilled phlebotomists were brought into teach the staff nurses this point of care testing. Ongoing attention to the technique, factors affecting the results, and periodic correlations with venous samples provide part of the quality controls built into the anemia clinics.

• Never underestimate the importance of iron. The protocols call for iron studies prior to initiation of ESAs and every 3 months. If iron depletion is noted, an automatic 5-week course of IV iron sucrose is given. Iron sucrose is easily and safely given in 200 mg doses using a 5-minute IV push method. It is physiologically not possible for ESAs to help attain and sustain a hemoglobin between 11 and 12 g/dL when iron is depleted (TSAT less than 20% and Ferritin less than 200 ng/ml). The protocol suggests that ESAs should not be administered until iron is restored to target levels and the hemoglobin is rechecked. The patient who is iron depleted can be assured that they will feel better with this therapy, in most instances the hemoglobin will rise as the iron is repleted, sometimes requiring little or no ESA therapy. Despite higher ferritin levels, the Dialysis Patients’ Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrates that if the patient has a low TSAT reading and is not responding to the ESA dosing, a course of IV iron may be warranted (Coyne et al., 2007).
• Monitor for other signs of ESA resistance. Several gastrointestinal bleeds have been identified early through our clinics. Some have been slow to develop and others more rapid, resulting in clinic to hospital admissions for transfusions and evaluations in some cases. Low albumin levels and inflammation are other causes of resistance to ESA agents (Kalantar-Zadeh et al., 2003). Gathering a diet history and providing patient education for dietary protein as well as monitoring for other signs of inflammation can aid in achieving target hemoglobin levels (11 – 12 g/dl, not to exceed 12 g/dl).
• Use the time that patients with CKD are in the clinic to educate. Staff members working in the anemia clinics are comfortable providing information on GFR, CKD stages, anemia, hypertension, diabetes mellitus, nephrotoxins, and dietary changes. Laminated cards are provided for this patient population requesting other health care providers to use hand veins to preserve upper arm blood vessels. Additionally, cards are given for other health care providers directing them to avoid or adjust doses in a specific group of medications to preserve existing kidney function.
• Continual review of the literature for changes and updates is essential. Protocols and practice within these anemia management clinics are evolving based on the analysis of data, newest research, as well as reimbursement standards. It is important to stay current and flexible so that the most safe, cost effective, and efficient patient care is delivered.