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Just Ask the Expert: Is the anemia of CKD always due to erythropoietin deficiency?
Veterinary internist Dr. Jennifer Garcia answers this reader query.
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At what stage of kidney insufficiency does low erythropoietin cause anemia? Does kidney failure need to be present? How can you tell if the anemia is secondary to low erythropoietin or something else? Can an erythropoetic agent such as epoetin alfa (Epogen—Amgen) be given empirically if you are not sure?
A. Historically, we know that anemia generally develops in the later stages of chronic kidney disease (CKD) in dogs and cats when azotemia is present.1,2 The term chronic kidney insufficiency is used for veterinary patients that have persistently isosthenuric urine but no overt azotemia, and I would not typically expect these patients to be anemic. Dilute urine may precede the development of azotemia because this occurs when about two-thirds of the functional nephrons are lost. Azotemia does not develop until three-fourths of the nephrons are lost.
Jennifer L. Garcia, DVM, DACVIM
If a patient is presented that has kidney insufficiency and a nonregenerative anemia, I would look for other causes of the anemia. The only way to confirm whether the anemia is secondary to low erythropoietin is to measure the concentration, and no commercial veterinary laboratories in the United States offer erythropoietin measurement.
In patients that have CKD, also remember that the anemia may be multifactorial. Gastrointestinal blood loss related to uremic gastritis may be a factor, as can poor nutrition and reduced red blood cell lifespan.3 Any evidence of melena, iron deficiency, or hemolysis may be other clues to look for in these patients. It is important to recognize and treat (e.g. gastroprotectants, proton-pump inhibitors, iron supplementation, B vitamins) other potential sources of anemia in these patients.
While erythropoietin replacement can be effective at increasing the red blood cell count in dogs and cats with anemia secondary to CKD, it is not without side effects, so patient selection is important. The primary concern with erythropoietic agents is that the patient will develop autoantibodies that lead to transfusion-dependent anemia. Newer products approved for use in people such as darbepoietin alfa (Aranesp—Amgen) are thought to be less antigenic because of differences in the formulation. This reduced antigenicity has yet to be definitively documented, but anecdotal evidence is promising, so I would reach for darbepoietin first in these cases.
When to start treatment in these patients is debatable. Most clinicians use a packed cell volume < 20% as the cutoff for initiating therapy, but this may vary from case to case. Recent evidence, however, suggests that earlier intervention is better and results in a better prognosis.4
Jennifer L. Garcia, DVM, DACVIM, is a veterinary internal medicine consultant in Houston, Texas.
1. Brown S. Evaluation of chronic renal disease: a staged approach. Compend Contin Educ Pract Vet 1999;21:752-763.
2. International Renal Interest Society. IRIS: 2009 staging of CKD. Available at: http://www.iris-kidney.com/pdf/IRIS2009_Staging_CKD.pdf.
3. Polzin DJ. Chronic kidney disease. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 7th ed. St. Louis, Mo: Elsevier, 2010;1990-2021.
4. Chakrabarti S, Syme H, Elliott J. Anemia predicts progression of chronic kidney disease in newly diagnosed azotemic cats, in Proceedings. Am Coll Vet Intern Med Forum, 2010.