Patients with chronic kidney disease often suffer from anemia. Anemia is a condition characterized by low numbers of circulating red blood cells. This condition is easily detected by measuring hemoglobin in the blood. Hemoglobin transports oxygen from the lungs to the rest of the body. Among patients with chronic kidney disease, low hemoglobin is often associated with symptoms of anemia. These symptoms of anemia include tiredness, fatigue, lack of energy or pep, feeling cold, and often leads to limited ability to perform physical activities.
How low should the hemoglobin be before the patient with chronic kidney disease experiences symptoms depends on the severity of the anemia and the activity level and tolerance of the patient. In the 1970s and 80s, anemia of chronic kidney disease was treated largely with blood transfusions. Blood transfusions in patients with chronic kidney disease pose risks beyond the transmission of blood-borne infection such as hepatitis.
This is because transfusions lead to the production of antibodies which can delay or preclude future ability to receive a kidney transplant. In 1989, epoetin was approved by the United States Food and Drug Administration (FDA) for reducing transfusions among patients with chronic kidney disease. With the introduction of epoetin, transfusion requirements fell dramatically and the patients had a noticeable improvement in the quality of life.
Results of Clinical Trials
In more recent years, physicians treating these patients thought that more normal hemoglobin levels may be associated with an even better quality of life and improved survival in these patients. There were several large clinical trials done to test this notion and 4 are especially notable because of their size. One trial was done among hemodialysis patients with previous cardiovascular disease—this was called the Normal Hematocrit Trial. Three trials were done in non-hemodialysis patients—these large trials and were called CREATE, CHOIR, and TREAT.
To the surprise of the physicians, compared to more conservative treatment of anemia, normalizing hemoglobin to near normal levels was associated with harm. There were more strokes, clotting events, heart attacks and deaths, and heart failure hospitalizations seen when hemoglobin was targeted to 13 g/dL or more. Furthermore, patients experienced more cancer related deaths if they had underlying cancer when they were treated to more normal hemoglobin levels. The FDA issued several warnings in response to these harms associated with the use of epoetin. Foremost among these warnings was to avoid targeting a normal hemoglobin. The FDA considers the lowest level of hemoglobin to reduce blood transfusion as the goal of epoetin therapy.
The package inserts recommend a target range of hemoglobin between 10 and 12 g/dL.
Patients who are being treated with epoetin should discuss the goals and targets of treatment of anemia with their physicians. They should tell their physicians of their symptoms and the improvement in symptoms with treatment. For example, should the symptoms of anemia resolve at hemoglobin of 10.5 g/dL for instance, there may be no need to increase it further to 12 g/dL by increasing the dose of epoetin. If, on the other one hand, a low dose of epoetin is needed and the patient has hemoglobin just outside the normal range (say 12.1), it may be okay to watch this hemoglobin.
On the other hand, if high doses of epoetin are needed to maintain this target, it might be reasonable to reduce the dose of epoetin or look for factors that may require such high doses of epoetin. A frequently missed factor is iron deficiency. Iron deficiency reduces the responsiveness of epoetin because it produces resistance to the increase in hemoglobin with epoetin. This can be easily treated with either oral or intravenous administration of iron.
What Patients Can Do
To make epoetin therapy safer, there are at least 3 other things that the patients can do while they are being treated. Since an increase in blood pressure is a common side-effect of epoetin use, the first is to obtain a home blood pressure monitor and to keep track of their blood pressure recordings at home. I recommend that the patients record their blood pressure in the morning when they wake up and before they good to bed. Measuring and recording blood pressure twice daily, every day, while they are on epoetin therapy can be an early warning sign of when things may be going wrong.
If the blood pressure goes up by 10 mm Hg systolic or 5 mm Hg diastolic, they should promptly contact their doctor. The second measure is to monitor hemoglobin and iron levels at frequent intervals. The FDA recommends that a rate of rise hemoglobin of 1 g in any two weeks is dangerous and, therefore, the dose of epoetin should be reduced so that such increases are treated early. Therefore, it is important to track changes in hemoglobin and iron at frequent intervals. Finally, if the patients have cancer or have had treatment for cancer, they should warn their doctors that they have had this condition. A checklist for talking points for patients appears in Table 1.
Communication between the physician and the patient is very important when treating anemia. Treatment of anemia is not simply about adjusting drugs. It may signal the presence of underlying conditions that may independently require treatment. Therefore, an open communication with the physician and some knowledge of how to use this drug safely is perhaps even more important for the patient who is being prescribed this medication. With joint responsibility, the symptoms of anemia can be effectively treated with drugs rather than transfusions.
- What are your symptoms and have they improved with treatment?
- At what level of hemoglobin did the symptoms improve?
- Is hemoglobin being monitored frequently (e.g. every 2 weeks)?
- What are your iron stores? Are they monitored frequently?
- Are you measuring your blood pressure at home and writing it in a diary? Is it controlled or increasing?
- Do you have cancer? Have you told your doctor about it?
About the Author
Dr. Agarwal is an internationally recognized leader in the area of clinical and translational research in nephrology. His foremost contribution has been in the area of hypertension in hemodialysis patients for which he is funded by the National Institutes of Health. He has refined the techniques to diagnose and treat hypertension in this complex group of patients. His current research also focuses on treatment of iron-deficiency anemia among patients with CKD for which is he is funded by NIH. He was a guest panelist in March 2010 at the Medical Evidence Development Coverage Advisory Committee to the Centers for Medicare and Medicaid Services (CMMS).
Article uploaded 1-6-2010
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