Anemia of renal disease: what it is, what to do and what's new

Abstract

Patient group: It is estimated that 15-30% of geriatric cats will develop chronic kidney disease (CKD), and that 30-65% of these cats will develop anemia as their renal disease worsens. Anemia of renal disease is multifactorial in its pathogenesis, but the main cause is reduced production of erythropoietin, a renal hormone that controls the bone marrow's production of red blood cells, as kidney disease progresses.

Practical relevance: It is important to recognize the presence of anemia of renal disease so that adequate treatment may be instituted to improve quality of life and metabolic function. Erythrocyte-stimulating agents (ESAs), such as epoetin alfa, epoetin beta and darbepoetin alfa, have been developed to counteract the effects of decreased erythropoietin production by the kidneys. These treatments, which are the focus of this review, have 83% similarity in amino acid sequence to the feline hormone. On average, the target packed cell volume (>25%) is reached within 3-4 weeks of ESA therapy.

Clinical challenges: The use of ESAs has been associated with a number of complications, such as iron deficiency, hypertension, arthralgia, fever, seizures, polycythemia and pure red cell aplasia (PRCA). Darbepoetin has a prolonged half-life compared with epoetin and thus can be given only once a week, instead of three times a week. The incidence of PRCA appears to be decreased with darbepoetin use when compared with epoetin use in cats.

Evidence base: There is limited published evidence to date to underpin the use of ESAs in cats. This review draws on the relevant publications that currently exist, and the authors' personal experience of using these therapies for over 5 years.

FIG 1

The anemia of CKD is typically normocytic, normochromic and non-regenerative. In this blood smear from a cat with longstanding anemia of CKD, acute gastrointestinal hemorrhage and iron deficiency, the RBCs demonstrate anisocytosis (variable sizes), polychromasia (younger RBCs have more grayish-blue color) and central pallor. Hypochromia is not commonly seen in cats compared with dogs with iron deficiency anemia. Wright-Giemsa, ×100. Courtesy of Andrea Siegel, ALX Laboratory

FIG 1

In the absence of oxygen, HIF-1α increases transcription of the erythropoeitin (EPO) gene, creating more EPO. EPO binds to its receptor on colony-forming unit-erythron (CFU-E) cells in the bone marrow and prevents apoptosis, enhancing proliferation and maturation to RBCs, which increase oxygen-carrying capacity. When oxygen is present, prolyl hydroxylase is stabilized and increases degradation of HIF-1α, preventing EPO production. HIF-1 = hypoxia-inducible factor 1, EPO R = erythropoeitin receptor

FIG 2

Colony-forming unit-erythron (CFU-E) cells have the highest number of erythropoietin (EPO) receptors. Blast-forming unit-erythron (BFU-E) cells and prorubricytes are also capable of responding to EPO

FIG 3

Ingested iron is absorbed from the duodenal lumen into the enterocyte through the divalent metal transporter (DMT-1) on the luminal side. In the absence of hepcidin, iron leaves the enterocyte on the basolateral side via ferroportin (cell A). Apotransferrin bound to iron is called transferrin, and is the main method of transporting iron in the circulation. Hepcidin binds to ferroportin, causing rapid internalization and degradation of ferroportin (cell B). Without ferroportin, iron efflux from the cell is prevented (cell C)

FIG 4

The PCV should be monitored weekly at the start of ESA therapy. Frequency of monitoring can be decreased once the PCV is stable and ESA dose adjustments are no longer needed

FIG 5

Because hypertension is a reported side effect of ESA therapy, blood pressure should be monitored at each visit, especially during the initial phases of treatment when the PCV is rising

FIG 6

Transfusion of whole blood or packed RBCs is the most rapid way to correct anemia of CKD and may be indicated if clinical signs of anemia need urgent treatment or if aggressive intravenous fluid therapy is anticipated and congestive heart failure is a concern

New methylene blue stained blood smear from a cat receiving darbepoetin showing multiple reticulocytes (RBCs with speckled blue stain uptake). Detection of reticulocytosis may be affected by sample timing. A decrease in reticulocyte count in conjunction with a decrease in PCV may portend development of PRCA. ×100. Courtesy of Andrea Siegel, ALX Laboratory

Bobby's pale mucous membranes are a classic sign of anemia