Anemia is defined as a reduction in the oxygen
carrying capacity of blood, measured in the laboratory as a low
hemoglobin concentratioin, or a low hematocrit (the percentage of the
blood volume that is occupied by red blood cells or erythrocytes). In a
normal person, the hemoglobin is approximately 13 grams per deciliter
and the hematocrit is approximately 40%.
Anemia is not a disease per se, but a reflection
of some other problem. It occurs when the balance between the normal
rates of blood loss and blood production is disturbed. There are three
basic mechanisms by which this occurs: (1) blood loss, (2) excessive
destruction of red blood cells (hemolysis), and (3) abnormally low
production of red blood cells by the bone marrow.
In a person with normal renal function, the
finding of anemia on routine blood analysis would prompt a work-up to
determine the ultimate cause. In chronic renal failure, anemia is almost
always present, and can be a result of any of the mechanisms listed
above. However, the typical “anemia of chronic renal insufficiency” is a
result of a decreased production of red blood cells by the bone marrow.
This defect in red blood cell production is
largely explained by the inability of the failing kidneys to secrete the
hormone erythropoietin. This hormone is a necessary stimulus for normal
bone marrow to produce red blood cells. In addition, other factors
associated with renal failure, including the accumulation of so-called
uremic toxins, may play a role in depressing bone marrow function.
Excess stores of aluminum may accumulate in the bone marrow of long term
dialysis patients and can contribute to anemia as well.
Blood 1oss and red blood cell destruction also
frequently contribute to the anemia in patients with renal failure.
Platelets, which are small constituents of blood which aid in blood
clotting, do not work normally in uremia. The defective blood clotting
seen in uremia makes bleeding more common. Rapid bleeding—from an ulcer
in the gastrointestinal tract, for example—causes a rapid decrease in
the hematocrit and is a medical emergency. Very slow loss of blood can
also cause anemia by depleting the body’s stores of iron, which the bone
marrow uses to produce blood cells.
Excessive destruction of red blood cells is also
seen in advanced renal failure. Normally, red blood cells survive for
about four months before being destroyed. This life span is reduced in
renal failure, probably because of chemical effects of uremia and
decreased flexibility of the red blood cells. This hemolysis is usually
mild and a person with a normal bone marrow could easily compensate for
it by increasing red blood cell production. However, in renal failure,
the bone marrow’s capacity to compensate is diminished.
What is the role of hemodialysis in the anemia of
chronic renal failure? The effectiveness of dialysis in reversing any
complication of uremia depends on the nature of that complication. Those
disturbances which are due to accumulation of a uremic toxin may be
reversible if that toxin is dialyzable and if the removal rate by
dialysis outstrips its generation rate. Some improvement in red blood
production is seen with initiation of dialysis, probably by decreasing
the toxic effect of uremia on the marrow. Dialysis, however, does not
replace the hormone producing functions of the kidney and therefore does
not by itself correct the main cause of anemia, namely deficient
production of erythropoietin. Dialysis does correct the bleeding
tendency seen in uremia, but not to normal.
Dialysis itself may also contribute to the anemia.
Iron deficiency can result from unavoidable dialyzer blood loss,
clotted dialysis membranes, and frequent blood sampling. Hemolysis may
occur if there are problems with the dialysate (temperature problems,
contamination with aluminum, fluoride, copper, chlorine, or chloramine).
Folate, a water soluble vitamin necessary for normal red blood cell
production, is dialyzable. Generally, dialysis patients are given oral
supplementation with folic acid in case their normal diet does not
supply them with sufficient folate to keep up with its loss through
dialysis.
Most patients tolerate chronic anemia fairly well.
In an otherwise healthy patient with chronic renal failure, a
hematocrit of approximately 25% is typical. The presence of other
medical problems, particularly heart and lung disease, can decrease a
patient’s ability to tolerate a lower blood count. Patients who have
undergone bilateral kidney removal (nephrectomies) often have
hematocrits which are significantly lower, probably because they cannot
make any erythropoietin at all. Patients whose kidney failure is a
result of polycystic kidney disease generally do not have anemia.
The treatment of the anemia of chronic renal
failure has changed dramatically in recent years. Until recently, the
principal treatments were transfusion of red blood cells and
administration of the hormone testosterone. Although transfusions will
rapidly correct a low blood count, repeated transfusions are associated
with some problems, including iron overload, the development of certain
antibodies, and the possibility of viral infections. Testosterone may
stimulate red blood cell production by the bone marrow, but the effect
is generally small, and its use is often associated with virilizing side
effects
In 1983, the gene for erythropoietin was isolated,
then cloned. Subsequently this led to the mass production of
erythropoietin and finally to its use in renal failure patients in 1990
(see Chapter 20). It is administered either intravenously at dialysis or
subcutaneously. In anemic patients with chronic renal failure,
treatment with erythropoietin is now standard practice and has
dramatically reduced the need for blood transfusions. The increase in
hematocrit seen with patients treated with erythropoietin has generally
resulted in improvement in exercise tolerance and overall sense of
well-being. It is important to moniter the iron status of treated
patients, as iron deficient patients will not respond appropriately to
administration of erythropoietin. The use of erythropoietin is
constrained by the extremely high cost of this hormone and the
reimbursement policies of insurance companies and Medicare.
To summarize, anemia is a universal complication
of chronic renal failure. It has multiple causes, the most important of
which is decreased production of erythropoietin by the kidney. The
availability of the recombinant form of this hormone is revolutionizing
treatment of this form of anemia.
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