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17/12/2018

#9 - THERAPY OF CHRONIC KIDNEY DISEASE (CKD) – Anemia




There are numerous causes that can cause anemia in dogs and cats with chronic kidney disease (CKD) in its advanced stages. Among the main causes needs to be remembered the nutritional deficiencies, bleeding through the gastrointestinal tract, reduced shelf life of red blood cells and lack of erythropoietin (hormone that helps regulating the production of new red blood cells). Nutritional deficiencies, common in patients with advanced stages of CKD, are often due to reduced food intake, vomiting and diarrhea, as well as blood loss through the gastrointestinal tract. It is possible that an iron deficiency associated with an altered BUN / Creatinine ratio results from a gastrointestinal bleeding. Intestinal bleeding is not always easy to identify and, if suspected, gastroprotective therapy may be useful. The trend of the patient's laboratory values (improvement of BUN and anemia) may be suggestive of the effectiveness of the therapy. Sucralfate can be used as a protector of the gastric mucosa, administered by mouth about 20 minutes before meals at a dosage of 0.5-2.0 g / dog based on the size and 0.25 g / cat. Iron deficiency should always be carefully evaluated, since there are several causes that can determine it. Many dogs and cats with chronic renal failure may in fact have a reduction in blood iron resulting from concomitant chronic inflammatory diseases. Iron can be administered by mouth as iron sulfate, although gastrointestinal disorders such as diarrhea are common. Other nutritional deficiencies may contribute to cause anemia, but their role in dogs and cats has not been studied in depth so far; however, folic acid ( a vitamin involved in red blood cells production) is often reduced in renal patients.

Erythropoietin (EPO) - is the most effective therapy for the treatment of anemia of renal origin although it can be associated with side effects at times. EPO is usually administered when patient’s PCV and / or hemoglobin gets, respectively, 20% and 8 mg / dL in cats or 22% and 9 mg / dL in dogs, or earlier if anemia becomes symptomatic. In both dogs and cats, chronic anemia in the course of CKD may be asymptomatic to extremely low hematocrit and hemoglobin values; probably this is due to a sort of adaptation to chronic "hypoxia", consequent to anemia. When EPO therapy is established, the goal is to achieve laboratory values ​​to make the patient clinically stable. In dogs and cats, hematocrit and hemoglobin values ​​to be achieved during therapy with EPO are respectively 23-25% and 9.5 mg / dL in cats and 25-27% and 10.5 mg / dL in dogs. If effective, therapy with EPO can correct anemia in 2-4 weeks; laboratory follow-up needs to be set after 15 days of therapy.

Most relevant side effect during therapy with EPO is antibody production, which inactivates EPO activity, causing a reduction in the formation of new red blood cells. To evaluate the adequacy of red blood cells formation, two laboratory tests are needed: the reticulocyte index in dogs and the presence of aggregate and punctuate reticulocytes cats. Production of anti-EPO antibodies usually does not occur before 4-8 weeks from the start of therapy and is often accompanied by reaction at the site of inoculation (EPO is administered by subcutaneous injection). Owners should be informed about the possibility of developing anti-EPO antibodies and the importance of reporting any discomfort, itching, redness, swelling in the inoculation area of ​​the drug. Another issue associated with EPO administration is hypertension: blood pressure should be measured at every follow-up visit.

It needs to be underlined many owners of dogs and cats report an improvement in appetite, increased resistance to physical activity and a better attitude to play of their animals.

Two types of EPO are available to treat of anemia in dogs and cats: recombinant human erythropoietin (rHuEpo) and darbepoetin alfa (DPA). Main advantages of DPA compared to human recombinant EPO are represented by

  • lower risk of antibody production
  • drug administration at longer intervals (it can improve compliance, particularly in cats and for owners nor comfortable with injections)..  

Evidence-based medicine

Treatment of anemia in the course of CKD improves patient's quality of life other than survival times. Recombinant human EPO or DPA therapy often results in patient's well-being and, more rarely, reduction of azotemia.

 



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