By Stephen Z. Fadem, MD, FACP

Many patients with chronic kidney disease (CKD) learn of their anemia because they feel weak and fatigued, or they are informed by their doctor. So, in this article we will answer some important questions to help patients assess whether they may be anemic.

What is Anemia?

Anemia is defined as a low red blood cell count. Since the red blood cells contain a molecule known as hemoglobin, we simply measure its concentration. If the amount of hemoglobin is less than 12 grams, the patient is said to be anemic. If the value is less than 11 grams, treatment is generally required.

But what does this really mean? The cells of the body are like tiny little gasoline engines. They too must burn fuel in the presence of oxygen to derive and capture the energy burst needed to perform all of their complex processes. While we do not do well with the carbon molecule, gasoline, our bodies breakdown carbon molecules – sugars and carbohydrates. The amazing part is how oxygen gets to each individual cell. This concept is known as the Bohr Effect, but is far from boring.

In our lungs, we breathe a percentage of oxygen in the air. That oxygen is attracted to the iron in the hemoglobin molecule. Iron and hemoglobin have a strong affinity for each other. It is interesting to note that the same process that makes our blood red also colors our rivers and mountains. This is something to keep in mind next time one passes beautiful scenery like the Maroon Belles or the Colorado River.

In the lung, the oxygen and hemoglobin are tightly bound together, but as the red blood cells travel to the cell, they lose interest in the oxygen and give it to the cell. This is because, at the cellular level, the environment has a lower pH, that is, it is more acidic. The affinity (a molecular type of love) of hemoglobin for oxygen lessens and releases oxygen. The hemoglobin molecules are more interested in the carbon dioxide, which is the “exhaust” from our little engines. Luckily, the chemical environment is just right, so the hemoglobin molecule inside each red cell gathers this carbon dioxide and takes it back to the lungs where it is literally blown off, or exhaled.

All circumstances must be right for oxygen to be able to make this journey to the cell and for the exhausts (carbon dioxide) to return back. Thus, the lungs must work properly, the circuit or blood vessel must be clear enough of debris so that the cells can pass freely, and there must be sufficient quantity of red blood cells with their precious essential ingredients of iron and hemoglobin.

It is not intuitive to think that the kidney, an organ better known for its production of urine, also plays a role in regulating the amount of red cells in the body. In nature, the amount of oxygen in the blood determines how fast red cells are produced. Low oxygen content in kidney cells stimulates the genes inside their center (nucleus) to synthesize the hormone necessary to turn on the bone marrow so it can produce red blood cells. If the oxygen content is high, then the factors that stimulate this process are automatically destroyed and recycled in kidney cells before they have a chance to perform their genetic magic. This keeps the system balanced, but always, some of the factor is able to get through to the genetic machinery of the kidney cell and produce the stimulating hormone.

This hormone is called erythropoietin (EPO). When it is produced by the kidney, it travels to the bone marrow and turns on the mechanisms that help red blood cells mature. Without EPO, the production of red cells is diminished.

What Causes Anemia in Kidney Disease Patients?

As the kidney becomes progressively diseased, mechanisms that form scar tissue take over, and with the process of scarring, cells responsible for manufacturing EPO die. These are the same cells that are under feedback control that increase in the face of hypoxia (lack of oxygen reaching body tissues) and decrease EPO production with enriched oxygen. Now, faced with becoming extinct, the production of EPO sharply decreases.

Anemia starts in the third stage of kidney disease when the glomerular filtration rate (GFR) is less than 60 cc/min, long before dialysis is necessary. Unfortunately, many patients come to the dialysis unit with anemia, even though it can be easily treated. As kidney disease progresses, anemia worsens.

What Are its Symptoms & Signs?

The onset of anemia in CKD is gradual and patients may not realize they have a problem. They may attribute fatigue and weakness to stress or not getting enough sleep. Patients who are anemic have less energy and enthusiasm. They do not want to finish projects because they are tired, weak and cannot concentrate. If the anemia is severe, dizziness may be present.

The blood pressure measurements in anemia may be low, but an even earlier sign is when the blood pressure measurement falls when standing and is relatively normal when sitting or lying down. A more subtle and even earlier change is a wide difference between the systolic (top) and diastolic (bottom) blood pressure measurements. The normal difference is around 50, but this pressure difference may increase with anemia. The reason for this is the heart tries to pump harder when the oxygen delivered to cells is low, and an accumulation of exhausts, such as carbon dioxide, will actually relax blood vessels and lower the diastolic pressure. Fatigue relates not only to a lack of adequate oxygen supply and metabolism at a tissue level, but to the build up of acids as cells shift to anaerobic or oxygen-free mechanisms to make energy. These are short-lived processes, but produce a great deal of acid in the tissues.

Family members may remark that the kidney patient looks pale. In particular, the conjunctiva (thin, clear, moist membrane coating the inner surface of the eyelid and outer surface of the eye) may look lighter in color. Dizziness, particularly when standing, may also accompany anemia. Patients with anemia have difficultly concentrating and focusing on a project and this may attract attention while on the job.

In patients who have cardiac failure, shortness of breath and fluid overload may appear. As previously mentioned, anemia forces the heart to pump harder and faster so the same net amount of oxygen will reach the tissues. If the heart cannot meet the demands of the body, heart failure may develop. Early heart failure may be associated with a dry cough, difficulty lying flat, or shortness of breath with exertion. The patient may have edema or swelling, particularly in the lower limbs. Heart failure is a serious problem. When the heart decompensates (loses the ability to maintain circulation), fluid can back up into the lungs and even the liver. This causes significant shortness of breath and is a medical emergency.

How Can I Detect Anemia?

Anemia can be detected by a simple blood test – hemoglobin level. This is performed as part of a complete blood count by a physician. Ortho Biotech Products, L.P., has developed the AnemiaPro Self-Screening Kit and in some circumstances it will be appropriate for patients to check their own hemoglobin levels. This test, when accompanied by information regarding your symptoms, can help the physician get started, but more importantly will help the patient to understand more about anemia, what it is, and how it needs to be treated. Whether patients check their own hemoglobin or a doctor does it, a result less than 12 grams in men and post-menopausal women or less than 11 grams in pre-menopausal and post-pubertal women, requires attention.

How Can Anemia Be Treated?

In most cases, the cause of anemia in kidney disease is the result of decreased production of EPO. Other factors can contribute to the anemia, such as low iron stores, chronic inflammatory conditions, or even subclinical blood losses from gastrointestinal sources (ulcers, tumors and gastritis), menstruation or dysfunctional uterine bleeding. Blood tests performed by your doctor can determine the cause of anemia and what additional testing and therapy is necessary. There are many other types of anemia and your doctor will want to be thorough to make sure a serious illness is not being overlooked.

Once the diagnosis of anemia in CKD is made, the therapy includes injections of the synthetic form of EPO. This can be given every week, two weeks or month. There are presently two formulations of EPO, epoetin alfa (ProCrit®) and darbepoetin (Aranesp®). Both are effective, and though one has a longer half life (time taken to be metabolized or eliminated), they are each in common usage by physicians treating kidney disease.

In addition, your physician will want to pay attention to your iron stores. The body cannot make red blood cells unless there is an ample supply of iron. However, since iron may be a source of danger in the face of an acute infection, you will need to be closely watched when receiving this supplement, either by mouth or injection. As the disease progresses, and by the time of dialysis, virtually all patients receive intravenous iron.

Summary

As the kidneys fail, they no longer manufacture a necessary hormone for the production of red blood cells. Since these cells are involved with the transfer of oxygen to all body tissues, anemia may cause fatigue, lack of concentration, pale skin, a fall in blood pressure when standing and dizziness. It may also cause heart failure to worsen. Since this hormone can be easily manufactured and obtained, it is most reasonable that early and aggressive treatment begin at its earliest onset. This can help improve quality of life and may also improve patient longevity. Education, awareness and screening at all levels of health care, but particularly the patient, are essential to avoid delays in the therapy of anemia in patients with CKD.

Stephen Z. Fadem, MD, FACP, serves as a vice president of the AAKP National Board of Directors and is a member of the AAKP Medical Advisory Board. He is a practicing nephrologist in Houston.

This article originally appeared in the December 2005 issue of Kidney Beginnings: The Magazine, Vol. 4, No. 5.

Back