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 Erythropoietin and Progressive Kidney Disease

Eli A. Friedman, M.D.

In a perfect world, every medical treatment would be backed up by solid science, that is, rigorous clinical trials. With well-designed trials, doctors and patients would know what treatments work best, how they work and why. In the world we live in, however, this level of scientific certainty is not always possible and, as a result, doctors must sometimes make treatment decisions based on personal experience or on sketchy or incomplete science.

The "off label" use of drugs to treat illnesses other than those for which they were approved or intended happens without scientific evidence of any benefit. We justify this by the desire to help patients for whom there are no scientifically established treatments. The use of penicillin for pneumonia is another example. No one questions that penicillin lowers the death rate in pneumococcal pneumonia, although no scientific studies to prove this have ever been done. But the alternative -- not using penicillin to treat pneumonia patients -- is unacceptable because the lives of untreated patients in the control ("placebo") group would be at risk.

A similar situation applies to the question of whether to give a synthetic hormone called erythropoietin to patients suffering from severe kidney ailments ("progressive renal disease"). These patients often are anemic, lacking sufficient red blood cells to carry oxygen from the lungs to the rest of the body. Doctors determine if you are anemic by calculating the hematocrit, the percentage of the blood that consists of blood cells, as opposed to plasma. A low hematocrit is a sign of anemia. Erythropoietin helps because it stimulates the bone marrow to make more red blood cells, thus raising the hematocrit. However, there have been no studies that prove that erythropoietin is safe and effective for those with progressive renal disease. Nevertheless, many doctors prescribe the drug for the anemia associated with kidney disease. In this article, we'll take a look at what we know and do not know about erythropoietin and kidney disease.

Current Kidney Treatments
Table 1 (below) shows the treaments that are most commonly used to slow down deterioration of the kidneys in people with kidney disease. Interestingly, only the first two, reducing high blood pressure and carefully treating diabetes, have been established as effective by clinical trials.

Table 1. Measures that Slow Progressive Renal17
  1. Bring down blood pressure18
  2. Maintain proper blood sugar levels (diabetes)19
  3. Limit dietary protein20
  4. Restrict dietary fat21
  5. Treat proteinuria (excess protein in the urine)22
  6. Stop smoking23
Table 2 lists the benefits of erythropoietin therapy for people with ESRD (End Stage Renal Disease), or those whose kidneys are actually failing.

Table 2. Benefits of Erythropoietin in Irreversible Renal Failure.24
  1. Enhanced brain function25
  2. Increased physical performance26
  3. Greatly improved quality of life27
  4. Prevention of a heart condition called progressive left ventricular dilatation28
  5. Reduced need for blood transfusions29
  6. Improved survival rate for those on hemodialysis/peritoneal dialysis30,31
There is a great deal of evidence that erythropoietin can help those with kidney failure1 One study found that treatment with erythropoietin before dialysis significantly increases survival rates in ESRD (End Stage Renal Disease).2 Based on this finding, most doctors now believe that erythropoietin therapy prior to ESRD treatment is a good idea.3

Erythropoietin in Nephrosis
Nephrosis, or nephrotic syndrome, is a condition that damages the blood-filtering parts (glomeruli) of the kidneys. More common in children under 9 years old, although it can occur at any age, nephrosis causes too much (or sometimes too little) protein to be released into the bloodstream which, in turn, produces water retention ("edema") most often noticed as swelling around the eyes, abdomen and legs. Anemia frequently occurs with nephrosis and studies on both adults and children indicate the superior effectiveness, compared to traditional treatments, of erythropoietin therapy.4,5

Erythropoietin in Diabetic Eye Disease
Early treatment with erythropoietin seems, in diabetic patients, to slow the onset of two eye conditions, diabetic retinopathy and macular edema, that can lead eventually, if untreated, to blindness.6-10 Erythropoietin treatment lessens the unwelcome effects of hypoxia (lower than normal levels of oxygen in the blood), a principal cause of diabetic eye disease.11-15

Table 3. Potential Value of Erythropoietin Pre-ESRD.
  1. Improves diabetic retinopathy (macular edema)
  2. Decreases stress on left ventricle
  3. Increases exercise tolerance
  4. Decreases fatigue and somnolence
  5. Enhances life quality
  6. Delays progression of renal disease
  7. Increases survival32

Conclusion
Today, most doctors agree that erythropoietin is an effective treatment for people with the anemia associated with progressive kidney disease. There is little question that erythropoietin can raise the level of the oxygen-carrying red blood cells (hematocrit) and have a beneficial effect. What is less certain is what hematocrit level doctors should shoot for and when to prescribe erythropoietin for patients with kidney disease. Based on what we know now, however, it seems that a hematocrit of 35-38% would be safe, effective, and in most cases, easy to attain.16

Erythropoietin therapy for those with progressive kidney disease, like any treatment that is not yet supported by the most rigorous possible scientific evidence, is in some ways a therapeutic gamble. There is always a chance that it may one day be discredited as ineffective or even harmful. On the other hand, the conservative "wait until proven" philosophy may deny a helpful -- or even life-saving -- therapy to an entire generation of patients.

November 2002 Email this article to a friend

References
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