Anemia and CKD

The decision to address anemia in the CKD patient is typically based on the degree of anemia, the likelihood of it correcting on its own, and the extent to which the patient is clinically affected. Although variable from patient to patient, the typical cutoff for strongly considering therapy is PCV <20%. Clinical signs such as weakness, lethargy and inappetence would be supportive of a need to address anemia.

Options for treating anemia of CKD include correcting underlying factors contributing to anemia, blood transfusion and administration of erythrocyte-stimulating agents (ESAs). Gastrointestinal hemorrhage, infection, or chronic inflammation are common underlying conditions contributing to anemia and should be addressed when possible. Identification and treatment of systemic infections may help improve anemia; urinary tract infections are particularly relevant in CKD patients and urine should be screened accordingly. Chronic gastrointestinal hemorrhage is suspected when melena, elevated BUN, iron deficiency or anemia disproportionate to the level of azotemia are noted. Empirical treatment with acid suppressants and sucralfate with a subsequent increase in hematocrit supports the diagnosis.

ESAs are commonly used to supplement the deficient erythropoietin hormone. Available ESAs include recombinant human erythropoietin Darbepoetin alpha (Aranesp) or Epoetin alpha (Epogen, Procrit). Darbepoetin is a longer-acting form of erythropoietin and is thought to have less association with anti-erythropoietin antibodies and pure red cell aplasia than the previously used Epogen.¹ Darbepoetin is currently the product of choice, but expense can limit its use for some owners (Walmart Specialty Pharmacy 877-453-4566, one ml vial [25 mg/ml] ∼$190). Therapy with Darbepoetin consists of an induction phase and a maintenance phase. The recommended starting dose is 1 mcg/kg SQ once weekly until the low end of the normal PCV range is reached, typically occurring within 3–4 weeks. Injections are then decreased to once every 2–3 weeks as needed to maintain PCV.²

Stimulating erythropoiesis is associated with a high iron demand and due to the functional iron deficiency associated with CKD, iron supplementation is recommended when therapy is initiated, as well as every few months through the course of therapy. Iron injections (iron dextran 50 mg/cat IM, typically well tolerated) are considered more ideal than oral iron supplementation as the latter tends to be bitter and likely to exacerbate an already poor appetite, as well as being poorly absorbed from the GI tract.² B vitamins are necessary for RBC synthesis and the degree to which they are deficient in CKD patients and an active contributor to anemia is poorly understood. Given their benign nature, supplementation is unlikely to be harmful but no information about efficacy currently exists. B vitamins are not considered effective as sole therapy for anemia.²

Blood pressure, as well as PCV, should be checked weekly during the initiation period; hypertension associated with too quick of an increase in PCV is the main side effect. Other reported side effects include pure red cell aplasia, arthralgia, fever, seizures, polycythemia and iron deficiency.² Previous estimates of treatment success in cats have been 60–65%.² Treatment failure may stem from a variety of causes including inadequate dose, owner compliance, GI bleeding, iron deficiency, B vitamin deficiency, concurrent infection or inflammation, aluminum toxicity, inhibition of erythropoiesis by ACE inhibitors, bone marrow dysfunction. Typical troubleshooting steps include increasing the dose, stopping ACEI and aluminum-based therapies (aluminum hydroxide, sucralfate), treating for GI bleeding or infection, and additional supplementation of iron and B vitamins.

Calcitriol

Calcitriol, the active form of Vitamin D, is produced in the kidney. Production is decreased in CKD and hyperphosphatemia further inhibits its synthesis. Calcitriol is an important inhibitor of parathyroid hormone and low levels lead to renal secondary hyperparathyroidism which has multiple deleterious consequences. In early CKD, controlling phosphorus levels may be sufficient to maintain levels. As kidney disease progresses, supplementation of calcitriol may be necessary. In dogs and people, supplementation of calcitriol has been shown to be beneficial, resulting in slower progression of disease; however, current evidence in cats is not supportive of supplementation.³ If used, calcitriol therapy is initiated at a dosage of 2.0–2.5 ng/kg daily and should not exceed 5 ng/kg/day. It should be given on an empty stomach as administration with food increases calcium absorption and the risk of hypercalcemia. Cost may be a concern for many owners as the drug and required monitoring are costly; careful monitoring of ionized calcium, phosphorus and PTH levels is required as hypercalcemia can result from over-supplementation.⁴ If hypercalcemia results, the daily dose can be doubled and given every other day to decrease intestinal absorption of calcium.⁴

References

1.  Chalhoub S, Langston CE, Farrelly J. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases. J Vet Intern Med. 2012;26:363–369.

2.  Chalhoub S, Langston C, Eatroff A. Anemia of renal disease: what it is, what to do and what's new. J Feline Med Surg. 2011;13:629–640.

3.  Sparkes AH, Caney SM, Chalhoub S, et al. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease. J Feline Med Surg. 2016;18:219–239.

4.  Polzin DJ. Chronic kidney disease in small animals. Vet Clin North Am Small Anim Pract. 2011;41:15–30.