ESA COMPLICATIONS
The administration of ESAs can create a number of complications in people, cats, and dogs, such as iron deficiency, hypertension,
arthralgia, fever, seizures, polycythemia, and pure red cell aplasia. In people, darbepoetin has a similar adverse event profile
to that of recombinant human erythropoietin.28
In people using ESA medications, hypertension is reported in 23%, cerebrovascular disorders in less than 1%, seizures in 2%,
and pure red cell aplasia in less than 1%.39 In one study on the use of recombinant human erythropoietin for the management of anemia in cats and dogs with renal failure,
hypertension was an adverse event with recombinant human erythropoietin administration in 40% to 50% of dogs and cats.19,40 In our experience, similar percentages are seen in dogs and cats receiving darbepoetin therapy. Hypertension secondary to
ESA therapy can be managed with a calcium channel blocker (amlodipine orally at 0.625 mg per cat or 0.1 mg/kg in dogs) or
an angiotensin-converting enzyme inhibitor (benazepril or enalapril orally at 0.5 mg/kg once daily). Blood pressure and creatinine
concentration should be rechecked one week after starting therapy.
Pure red cell aplasia in people, cats, and dogs is caused by the production of neutralizing antierythropoietin antibodies
that cross-react with all ESAs, as well as with endogenous erythropoietin.41 It is characterized by severe, nonregenerative anemia with an almost complete lack of bone marrow red blood cell precursors.
The antibodies can remain in the body for more than eight months, and all patients become transfusion-dependent.3 Antierythropoietin antibodies are directed against the protein backbone, so although the amino acid sequence is about 85%
identical, the lack of complete homology is thought to be the cause of the increased rate of pure red cell aplasia in animals
compared with the rate in people. Pure red cell aplasia seems to occur at an incidence of 25% to 30% in dogs and cats receiving
human-derived ESA.40,42 In our experience, the occurrence of pure red cell aplasia seems to be much lower with darbepoetin administration than with
recombinant human erythropoietin, with a frequency of less than 10%. Pure red cell aplasia is difficult to treat and can last
for many months. Treatment involves stopping therapy with ESAs, administering blood transfusions as needed, and possibly beginning
immunosuppressive therapy with prednisone and cyclosporine or other immunosuppressive drugs.43,44
ESA TREATMENT FAILURE
Failure to reach the target PCV with ESA treatment can be caused by a number of factors, such as iron deficiency, anemia of
chronic inflammation, concurrent illnesses, infections, hemorrhage from gastrointestinal erosions or ulcers, bone marrow failure
or fibrosis, and pure red cell aplasia (Figure 1). Thus, it is important to diagnose and treat concurrent diseases and monitor for evidence of pure red cell aplasia.
CONCLUSION
Renal disease anemia is multifactorial in its pathogenesis. It is important to recognize it so adequate treatment may be instituted,
as quality of life and metabolic function may be decreased as a consequence of worsening anemia. Multiple therapies are available;
however, administering ESAs and eliminating other potential causes of anemia seem to be the most efficient long-term therapies.
Serge Chalhoub, DVM, DACVIM*
Cathy Langston, DVM, DACVIM
The Animal Medical Center
510 East 62nd St.
New York, NY 10065
*Dr. Chalhoub's current address is Charleston Veterinary Referral Center, 3484 Shelby Ray Court, Charleston, SC 29414.
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