ANEMIA: INADEQUATE RED BLOOD CELLS
Red blood cells are basically little microscopic bags of hemoglobin. They have no nucleus and thus no DNA. They have no internal structures and thus no ability to perform complicated metabolism. Despite their simplicity, their function is crucial: they carry hemoglobin, the iron-containing complex protein that allows for oxygen transport to the tissues (as well as carbon dioxide transport to the lung for removal). Inadequate red blood cell quantity means inadequate hemoglobin which means inadequate oxygen delivery. In the whole patient this translates to lack of energy, poor appetite, pallor, basically an important reduction in life quality.
There are three important ways in which the kidney patient loses red blood cells. The first way is bone marrow suppression. The second way is bleeding. The third way is called “hemodilution.” We will review all these and what can be done about them. Maintaining a stable red blood cell quantity keeps the patient energetic and spirited and is crucial to staying alive.
BONE MARROW SUPPRESSION
One of the functions of the kidney is the production of the hormone called “erythropoietin” (pronounced “Urithro-po-eetin”). This hormone, often simply referred to as “Epo,” represents the command to the bone marrow to make more red blood cells. When the kidney is damaged, its ability to produce erythropoietin is compromised. Red cells are still produced but over time the red cell count drops.
Blood sample in a PCV tube being read against a chart
A simple measurement of red blood cell count is called the “packed cell volume” or “PCV.” The packed cell volume is an expression of the percentage of the blood’s volume which is taken up by red blood cells. It can be measured using only a drop or two of blood and can be done “while you wait” in any veterinary office. The sample is spun in a machine called a “centrifuge” to separate the red cells, white cells, and serum. The blood tube is then read against a chart to get the packed cell volume. “Hematocrit” or “HCT” also measures the volume of blood present as red blood cells but uses a measure of hemoglobin to determine it. Practically speaking, PCV and Hematocrit measure the same thing.
An oral iron supplement must be given simultaneously so that the bone marrow will have the building blocks necessary to make red blood cells.
In a presentation by Dr. Sheri Ross at the 2006 meeting of the American Collee of Veterinary Internal Medicine, she notes that in one study of dogs and cats with naturally occurring kidney failure, 2 of 3 dogs treated with erythropoietin for >90 days and 5 of 7 cats treated for >180 days developed refractory anemia that was attributed to anti-erythropoietin antibodies. A clinically significant immunologic reaction to erythropoietin has been reported to occur in 20-70% of treated veterinary patients. A more commonly published statistic is that antibody production is a problem in 30-40% of pets using human erythropoietin but this complication poses a sobering thought. It is important not to use this hormone at the first sign of anemia but wait until it is really and truly needed.
Is Darbepoetin better than Erythropoietin?
Darbepoetin is a synthetic hormone meant as an improvement over the natural hormone, erythropoietin. The synthetic version lasts longer and is less antigenic (less likely to create any erythropoietin antibodies). Cost is similar to erythropoietin and since most veterinarians have experience with erythropoietin, this is what tends to be prescribed. Further, dosing for animals is still being worked out though there are some guidelines based on human conversions between darbepoetin and erythropoietin. It appears that the changes made in the amino acid sequence have made darbepoetin less likely to generate anti-erythropoietin antibodies but in a patient that is already having a problem with antibodies, darbepoetin is close enough to Epo to be inactivated as well.
For further information on Erythopoietin click here.
The calcium-phosphorus imbalance that goes with renal disease is reviewed elsewhere in this center but the bottom line is that the excess blood phosphorus that results in renal insufficiency leads to demineralization of bone and mineral deposits in soft tissues. Mineralization is inflammatory and, when it occurs in the GI tract, it leads to bleeding, ulceration, and pain. The renal patient cannot afford appetite loss, nausea or further blood loss so special treatment is needed while other efforts are made to control phosphorus levels.
Beyond the phosphorus level, another problem is a hormone called “gastrin.” Gastrin is a hormone involved in food digestion and is a stimulus for the stomach to release acid. Normally, when the need for gastrin has passed, the kidney removes it from the circulation but in the kidney patient gastrin is not efficiently removed. The prolonged presence of gastrin also prolongs the stomach’s secretion of acid which can lead to ulceration.
How do we know there is stomach/intestinal ulceration?
There are several clues on the lab work an in the patient’s physical appearance that tell us that additional therapy is needed to control this kind of blood loss.
What can we do?
Medications for nausea and appetite stimulation can be used. The most important treatment, of course, is going to be control of the phosphorus level. Other treatments include the following:
Pets presenting to the vet’s office in Stage IV or late Stage III kidney failure are often dehydrated. A typical scenario is a pet that had been drinking lots of water and eating fairly well suddenly stops eating and is listless. Possibly it is even noticeable that the pet has lost weight (though this is often erroneously attributed to age). The owner waits a day or two to see if the pet will start eating again and get better on its own and when that does not happen, the pet is brought to the vet. Once the diagnosis of kidney failure is made, fluid therapy will be recommended, possibly fairly aggressively to drive the toxin levels down quickly. Unfortunately, the fluid therapy that is so helpful for driving toxin levels down, also will dilute the blood and drive the red blood cell count down.
This is not a big problem if the patient is not particularly anemic to begin with but if the patient is already low on red blood cells or if fluid therapy is very aggressive, by the end of hospitalization (or even in the middle of it), the patient may be feeling the low red cell count.
What can be done?
One choice is to be less aggressive with the fluid therapy though this means a longer time to get to a livable toxin level. Another choice is the use of erythropoietin as above, possibly in addition to a less aggressive fluid administration rate. Using erythropoietin helps at least increases the red blood cell production to balance the dilution that comes with rehydration of the patient.