Anemia of CKD is typically nonregenerative, normochromic, and normocytic. The anemia is normally proportional to the degree
of nephron loss. Deformed red blood cells (echinocytes or burr cells) may be noted.
The cause of anemia of CKD is multifactorial. The primary mechanism is an absolute or relative loss of erythropoietin, a hormone
produced by the kidney that stimulates red blood cell progenitor cells to begin erythropoiesis in the bone marrow. In one
study, dogs with CKD had low to normal erythropoietin concentrations despite being anemic, which is an inappropriate response
to anemia.27 In cats with anemia of CKD, erythropoietin concentrations may be in the normal range.28 A diagnostic problem is that erythropoietin assays are not readily available commercially.
Other mechanisms of anemia include shortened red blood cell lifespan, nutritional abnormalities, erythropoietic inhibitor
substances in uremic plasma, blood loss, and bone marrow fibrosis secondary to a previous insult to the marrow.1 Additional clinically important causes of anemia in dogs and cats with CKD are iron deficiency and chronic GI blood loss.
Iron deficiency can be detected by evaluating a serum iron panel (Table 3), by staining bone-marrow biopsy samples for iron content, or through response to iron supplementation. Serum iron concentrations
can be low with iron deficiency but also with inflammatory disease. Serum ferritin is an acute phase reactant protein, which
may be elevated with inflammation. Patients with anemia of CKD may have a combination of iron deficiency, anemia of chronic
inflammation, and erythropoietin deficiency, making interpretation of an iron panel difficult.29
Table 3: Interpretation of Iron Panel Results*
A gradual decrease in the mean corpuscular volume (MCV) may indicate development of iron deficiency. Mean corpuscular hemoglobin
(MCH) may also decrease, and the mean corpuscular hemoglobin concentration (MCHC) is the last of the red blood cell indices
to decrease.1 The reticulocyte hemoglobin content and reticulocyte volume can be evaluated with automated complete blood count machines
in reference laboratories, but these values are not routinely reported. Initial reports indicate these may prove to be useful
in evaluating for iron deficiency, but more work remains to validate these tests.30,31
An elevated BUN:creatinine ratio in conjunction with sudden development of anemia may be a clue that GI blood loss is present.
An increase in hematocrit and a decrease in the BUN:creatinine ratio after treatment with gastroprotectant medications (e.g. H2-blockers, proton-pump inhibitors, or sucralfate) provides evidence of GI hemorrhage as a cause of the anemia.