Epoetin Alpha and Darbopoetin Alpha May Not Be as Safe as Previously Believed

The erythropoiesis stimulating drugs epoetin alpha and darbopoetin alpha are medications used to increase red blood cell production in people who may have low levels of the naturally human body produced hormone which functions in the same manner and is called erythropoietin. I have seen many chronic kidney disease patients who are on this medication, because the human kidneys produce erythropoietin and the level of this hormone is decreased in chronic kidney disease. However, a recent commentary in the New England Journal of Medicine in early 2010 raises questions about the effectiveness of these medications, and even whether they do more harm than good.

Are Erythropoiesis Stimulating Drugs Safe?

A person with chronic kidney disease may develop a below normal hemoglobin level, and for decades this abnormal hemoglobin level, otherwise known as anemia, was believed to cause a variety of health conditions in patients with chronic kidney disease, which include left ventricular hypertrophy or enlargement of a chamber of the heart, in addition to changes in cognition. The use of epoetin for anemic chronic kidney disease has helped to decrease the number of blood transfusion these patient may need if they become severely anemic.

Although hemoglobin levels in the normal range are though to be healthier than lower hemoglobin levels in chronic kidney disease patients and in all patients, the proof, as always is in the pudding. In this case, the proof was sought in the form of randomized clinical trials comparing the treatment of patients with these so-called erythropoiesis stimulating drugs when compared to patients not receiving these medications. In brief, the trials showed increased cardiovascular risk in patients receiving an erythropoiesis stimulating drug, such as epoetin alpha, when compared to patients who did not receive this medication. Many different explanations have been raised for this disparate findings, including the possibility that raising the hemoglobin level too fast may lead to increased risk of cardiovascular disease.

The commentary noted that the target hemoglobin levels for chronic kidney disease patients may be harmful, and that there is a lack of information concerning if a higher, or lower, target hemoglobin level would reduce the risk of these medications. The authors call for randomized clinical trials to determine the best dosing of these medications, as well as how frequently patients should be monitored.

Is There a Better Way to Deliver These Medications to Patients?

I remembered what my endcrinology professor told me in college when I read this article, which was that the administration of exogenous hormones (such as epoetin), can never be done in a manner which is physiologically normal. Meaning that the administration of medications which are also native human hormones, such as insulin and epoetin, will not be introduced into the blood stream in exactly the same manner as the human body secretes these hormones. In fact, these "artifically produced hormones" may have devastating consequences for the patient and produce serious side effects due to their use a medications.

Indeed, diabetic patients have long be exposed to the fluctuations of their blood sugar due to "shots" of insulin given during the day. Because of this phenomenon the more sophisticated insulin pump was invented to deliver insulin in a more phsyiological manner, i.e. more continuously rather than in shots. In this way, the insuin pump tries to mimic how the human body delivers insulin to its cells, the human body actually secretes insulin in a continuously changing fashion in response to variety of factors including digestion of food.

Could an "epoetin" pump be constructed which released these erythropoiesis stimulating drugs in a more physiologically adaptive manner? Possibly, one would have to study how erythropoetin is normally secreted in the human body and attempt to mimic this. The authors themselves note that the eratic changes in hemoglobin level may part of the increased risk of cardiovascular factors such as heart attacks, could a steady infusion of epoetin eliminate this problem? Only research and clinical studies will be able to answer this question.

Sources:

http://healthcarereform.nejm.org/?p=2636&query=home

http://emedicine.medscape.com/article/238798-overview