Treatment of Anemia in Patients with Chronic Kidney Disease

What is the problem and what is known about it so far?
Patients diagnosed with Chronic Kidney Disease (CKD) often develop anemia (insufficient red blood cells). The anemia of CKD was treated with blood transfusions until erythropoietin was manufactured in the 1980s. Erythropoietin is a hormone normally produced by the kidneys that regulates red blood cell production. In CKD the kidneys do not produce sufficient erythropietin to maintain enough red blood cells. Hemoglobin is the oxygen transporter found in red blood cells. With a decrease in red blood cell production there is a decrease in oxygen delivery by hemoglobin to the body. Current recommendations are to give erythropoietin to patients with CKD, when the hemoglobin value falls below 9 g per deciliter (normal range is approximately 12-16 g per deciliter) because it was believed, that a low hemoglobin is a risk factor for the development of cardiovascular complications, and death. Also, erythropietin has reduced the need for blood transfusions, has improved quality of life and reduced the need for hospitalization in CKD patients. The optimal target hemoglobin, however, remains controversial.

Why did the researchers do this particular study?
In the Correction of Hemoglobin and Outcomes in Renal Insufficiency (referred to as the CHOIR study), researchers set out to determine whether achievement of a higher hemoglobin level of 13.5 g per deciliter would decrease the risk of cardiovascular complications and death, as compared with lower hemoglobin of 11.3 g per deciliter.

Who was studied?
The study group enrolled 1432 patients with chronic kidney disease at 130 sites in the United States.

How was the study done?
The researchers randomly assigned patients to one of two groups: 715 patients were assigned to a high-hemoglobin group (target level 13.5 g per deciliter), and 717 patients were assigned to a low-hemoglobin group (target level 11.3 g per deciliter). The researchers then observed the patients for changes in time to death, heart attacks, hospitalization for congestive heart failure and stroke. Three questionnaires were used to assess changes in quality of life. The patients were followed for 36 months.

What did the researchers find?
Patients in the higher hemoglobin group had an increased risk of death, heart attack, hospitalization for congestive heart failure, and stroke, with no improvement in quality of life as compared to patients in the low-hemoglobin group.

What were the limitations of the study?
The potential limitations in this study included the fact that many patients did not complete the study and more of these came from the low-hemoglobin group. However, the researchers felt that these problems were addressed, and that the study results were valid.

What are the implications of the study?
Patients receiving erythropoietin for treatment of anemia seem to do better when their target hemoglobin is maintained in a range of 11-12 grams per deciliter. Achieving a higher hemoglobin, close to the normal range, does not improve a patient’s quality of life and may be associated with an increased risk of death, heart attack or hospitalization for congestive heart failure and stroke.