Why do people with kidney disease develop low blood count (anemia)? How do you treat it?

For many of my patients, it is hard to see the connection between chronic kidney disease (CKD) and low red blood count, or anemia. The two entities just seem so disconnected that one wonders, what would one have to do with the other? The key to appreciating this link is recognizing two fundamental principles; one, that the function of the kidneys extends to beyond just "making urine", and two, kidney disease has numerous repercussions that affect multiple organ systems. Well, one of these organ systems happens to be your body's machinery that makes red blood cells, known as the hematopoietic system. And the reason this machinery gets affected in kidney disease is because of the kidneys' function in producing a hormone called, erythropoietin.


HOW DOES ANEMIA DEVELOP IN CKD?

Erythropoietin, also known as "epo" in short, is an essential hormone without which the body cannot produce red blood cells (RBCs). Most of RBC production in adults occurs in the bone marrow, although the liver and spleen are also capable of doing that. However, to stimulate the marrow to make RBCs, you need an important signal. That signal is epo. The majority of the epo production occurs in the kidneys, with a very small proportion being produced in the liver. When your kidneys sense a deficiency of oxygen in the blood (due to inadequate RBCs), they start pumping out epo in to your blood stream. Hence, when the kidney function goes down, epo production is reduced as well. Consequently, low RBC counts develop, which is called anemia. Patients with anemia can have a multitude of symptoms including fatigue, loss of appetite, chest pain, shortness of breath, and heart attack/heart failure in extreme cases. 


Red Blood Cells (RBCs) in action
Image courtesy of Victor Habbick/ FreeDigitalPhotos.net


Lack of epo is not the only reason for development of anemia in CKD. Anemia can also develop from other causes that typically coexist in patients with kidney disease. The life span of RBCs may itself may be reduced in the blood. Patients with advanced kidney disease can have a tendency to bleed. Finally, patients with kidney disease can be in a constant state of "inflammation" that can make it hard for the body to absorb iron from the gut, and utilize it even when adequate iron is present in the body. 



TREATMENT OF ANEMIA OF KIDNEY DISEASE

In the 1950s, researchers were able to understand the role of epo in the body, and the fact that the kidneys were the main production site for this hormone. However, it was not until 1983 that scientists were able to artificially synthesize human epo in a lab, and mass produce it for use as a medication. This suddenly opened up a new avenue for treatment of anemia in patients with kidney disease. Before the advent of epo, kidney disease patients with severe anemia would typically receive frequent blood transfusions. This came with its own set of risks, including transmission of diseases like HIV and Hepatitis C. In fact, it was not until 1992 that blood for transfusion was universally screened for Hepatitis C with high sensitivity tests.   

Understandably, synthetic epo is a part of the regimen used to treat anemia in patients with kidney disease. Typically patients who are not on dialysis can be started on epo injections that can be administered every two weeks. Patients can do this at home since these are subcutaneous shots, just like insulin. But a few important things that need to kept in mind before prescribing epo in a kidney disease patient are:


  • Other causes of anemia need to be ruled out. These include malabsorption, occult bleeding, heavy menses in women, etc. Kidney disease could often be just a red herring masquerading as the cause of anemia. 
  • Nutritional deficiencies must be corrected before someone is started on epo. For instance if you are iron deficient, and have low iron levels in the blood or bone marrow, epo supplementation would not do much. Iron is one of the "raw materials" required to make RBCs. If you don't have that, you can push your bone marrow as much as you want using epo, but you are not going to increase your blood counts without correcting the iron deficiency first. 
  • Epo might not be for everyone. It has numerous side effects. Some serious ones are elevation in blood pressure, heart attacks, and strokes. Epo essentially increases your blood's viscosity and can cause headaches. Some people can suffer severe anaphylactic reactions. Too high blood counts from use of epo are especially dangerous, and hence, treatment is best left to a specialist who will know exactly when to stop "too much of a good thing". 



EPO AND DOPING IN SPORT 

The fact that synthetic epo could be used to increase the blood count, and hence, theoretically increase the oxygen carrying capacity of the blood gave all the wrong ideas to the physicians and scientists who ply their trade in the world of sport doping (obviously!). The practice is largely believed to have originated in the 1990s in Italy, and was exacerbated by the fact that no lab test existed to detect artificial epo in an athlete's blood stream until 2000. Hence epo came to be used as a much sought after performance enhancing drug in endurance sports.


Image courtesy of Tom Curtis/ FreeDigitalPhotos.net


It was a part of the cocktail of drugs that cyclists like Lance Armstrong were later found to have used. The American author and poet, Edgar Allan Poe would turn in his grave if he realizes that the world of sport doping has appropriated his name as a code for epo. Today, in these secretive circles, the words, "Edgar", "Poe", and "Edgar Allan Poe" are spoken in hushed tones to refer to erythropoietin! 


Veeraish Chauhan, MD, FACP, FASN
Nephrologist
Sarasota/ Bradenton, FL  

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