The standard practice for treating anemia in patients with chronic kidney disease is being reviewed in light of new evidence and a possible conflict of interest.

Erythropoiesis-stimulating agents (ESAs), also known as recombinant human erythropoietin and sold as Procrit and Epogen (both epoetin alfa) and Aranesp (darbepoetin alfa), provide a protein that stimulates the production of red blood cells and raises blood hemoglobin levels. Anemia is common in people with chronic kidney disease, and treatment with an ESA can prevent the need for blood transfusions and improve the quality of patients' lives. The Kidney Disease Outcomes Quality Initiative (KDOQI) panel of the National Kidney Foundation (which receives financial support from the makers of ESAs) set target hemoglobin levels at 11 to 13 g/dL, yet the optimal dose had not been defined by randomized trials.

In November 2006, the Food and Drug Administration (FDA) issued an advisory on the use of ESAs in the treatment of anemia, warning that hemoglobin levels of higher than 12 g/dL can increase the risk of serious complications. The recommendation followed the early termination by a safety review committee of the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study when results showed that administering epoetin alfa to reach a hemoglobin level of 13.5 g/dL, as compared with 11.3 g/dL, resulted in a higher risk of death, heart attack, stroke, or hospitalization for congestive heart failure.

In the CHOIR study, 715 of 1,432 patients with chronic kidney disease who were not undergoing dialysis received epoetin alfa to achieve a hemoglobin level of 13.5 g/dL, while the rest were treated to reach a hemoglobin level of 11.3 g/dL. The groups experienced similar improvements in quality-of-life scores, but those in the high-hemoglobin group had a 34% higher risk of death or cardiovascular complications. The CHOIR researchers concluded that anemia in patients with chronic kidney disease should be corrected to a hemoglobin value of 11 to 12 g/dL "because of increased risk, a likely increased cost, and no quality-of-life benefit" associated with correction to a higher lever (11 to 13 g/dL).

The experts behind the CHOIR trial expected higher hemoglobin levels to lower the risk of cardiovascular disease and death. Because the results showed the opposite, the leader of the CHOIR study, Ajay Singh, clinical chief at Brigham and Women's Hospital Renal Division, led an initiative that prompted Partners HealthCare in Boston, the nonprofit owner of Brigham and Women's, to set new dosing guidelines for ESAs to keep hemoglobin at a safe level.

The KDOQI panel met in February to review the new findings and discuss their implications. According to Kerry Willis, vice president for medical and scientific activities at the National Kidney Foundation, "When the anemia work group completes its analysis of new studies, appropriate announcements or publications will be developed."

Patients versus profits? More than 40% of dialysis patients in 2006 had hemoglobin levels higher than 12 g/dL, according to the U.S. Renal Data System, a registry of dialysis patients. Because Medicare pays for ESAs separately from dialysis services, dialysis centers can make more money by treating patients with more epoetin alfa, providing no incentive to lower the dose. In 2005 Medicare spent $2 billion on epoetin alfa, making it the drug associated with the highest costs under Medicare Part B.

According to a report in the December 28, 2006, Boston Globe, some for-profit dialysis companies say they won't change their guidelines for administering ESAs because they believe that the CHOIR results do not apply to them because the study's patients were not on dialysis. "That argument does not consider the evidence in its totality," Singh told AJN, referring to studies of ESA use in dialysis patients published in 1998 and 2005 that produced results "remarkably concordant with CHOIR."

In December 2006, Singh testified before the House Committee on Ways and Means to urge that Medicare bundle payment for ESAs and other injectable drugs with dialysis to remove the incentive for overtreatment. And in February the FDA issued an alert warning against using Aranesp to treat anemia in patients with cancer who are not receiving chemotherapy. A study showed that treatment with Aranesp did not reduce the need for blood transfusions but was associated with a higher mortality rate, compared with patients who received a placebo. The FDA notes that "an ESA may offer no benefit and could have a chance of serious harm." For details, see http://www.fda.gov%2fmedwatch%2fsafety%2f2007%2fsafety07.htm%26%2335%3bESA.