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Basics ⬇

Basics

Definition

Progressive decreases in PCV, RBC count, and hemoglobin and hypoplasia of erythroid elements of the bone marrow are predictable features of progressive CKD. Anemia is normocytic, normochromic, nonregenerative, and proportional to the stage of CKD. The underlying cause of the anemia of CKD is multifactorial. Although factors such as gastrointestinal blood loss, reduced red blood cell survival, deficiencies in iron and/or folate, cytokines and inflammatory mediators may be involved, the primary contributing factor to anemia of CKD is an inadequate production of erythropoietin (EPO) by the kidneys. Erythropoietin is a glycoprotein hormone that regulates red blood cell generation at the level of the bone marrow. Erythropoietin is produced in the peritubular interstitial cells of the kidney in response to decrease in tissue oxygen.

Signalment

Middle-aged to old dogs and cats mostly affected; seen in young animals with heritable, congenital, or acquired CKD.

Signs

  • Anemia contributes to development of anorexia, weight loss, fatigue, lethargy, depression, weakness, apathy, cold intolerance, and behavior and personality changes characterizing CKD.
  • Pallor of the mucous membranes.
  • Tachypnea.
  • Tachycardia.
  • Systolic murmur.
  • Syncope and seizures (rare).

Causes & Risk Factors

  • All inherited, congenital, and acquired forms of CKD (e.g., pyelonephritis, glomerulonephritis, amyloidosis, polycystic kidney disease, and lymphoma).
  • Exacerbated by iron deficiency, inflammatory or neoplastic disease, gastrointestinal blood loss, hemolysis, and myeloproliferative disorders.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Anemia of chronic infectious, inflammatory, or neoplastic disease; myeloproliferative disease; chronic blood loss; aplastic anemia; endocrine disease; drug reaction; and chronic immune-mediated, toxic, viral, rickettsial, or parasitic anemia; hemodilution.
  • Regenerative anemia excludes diagnosis of anemia of CKD.
  • Generally masked until advanced CKD.

CBC/Biochemistry/Urinalysis

  • Normocytic, normochromic, hypoproliferative anemia (progressive; anemia may be masked by dehydration).
  • Reticulocytes-low corrected indices and absolute counts ( 10,000/µL).
  • Moderate to advanced CKD-elevated BUN, creatinine, and phosphorus; variably high calcium; variably low bicarbonate and potassium.
  • High BUN:creatinine ratio may predict concurrent” gastrointestinal blood loss.
  • Impaired urine-concentrating ability, possible proteinuria, and variably active sediment.

Other Laboratory Tests

  • Serum iron-normal or variably low.
  • Transferrin saturation-normal or variably low (<20%).
  • FeLV and FIV and/or haemobartonella testing (cats) or rickettsial titers or PCR (dogs) to exclude agent-induced myelodyscrasia.
  • Serum erythropoietin-normal (inappropriately) or low.

Imaging

  • Small, irregular kidneys with loss or disruption of renal architecture detected by radiography or ultrasonography.
  • Enlarged, polycystic, hydronephrotic, infiltrative.

Diagnostic Procedures

Cytologic examination of bone marrow-erythroid hypoplasia; myeloid:erythroid ratio normal or high; stainable iron normal or variably low.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s) and Fluids

Blood Transfusion

  • Short-term, rapid correction if hypoxic distress (typically PCV 15%)-give compatible whole blood or packed RBCs.
  • Target PCV is 25–30%.
  • May be given intermittently for prolonged management, although compatibility issues are likely to occur long term.
  • EPO support for progressive or symptomatic anemia (dogs, PCV 25%; cats, PCV 23%).

Erythropoietin Replacement

  • Epoetin alfa (r-HuEPO)-original synthetic erythropoiesis stimulating protein, replica of human erythropoietin (Epogen and Procrit); provides consistent, rapid, and long-term correction of anemia in dogs and cats with CKD; potential for anti-r-HuEPO antibody production and pure red cell aplasia.
  • Darbepoetin alfa (Aranesp), a new hyperglycolylated analogue of r-HuEPO with prolonged half-life and sustained effects; very effective with significantly less tendency for antibody induction; should be used preferentially to epoetin alfa.
  • Target PCV-dogs, 30–35%; cats, 30%.
  • Initial dosage: darbepoetin alfa-0.5– 2.0 µg/kg SC/IV once weekly until PCV reaches low end of target, then decrease to q2–4 weeks as needed to maintain target. Recommend PCV prior to EVERY injection to avoid overtreatment.
  • Epoetin alfa-50–100 U/kg SC thrice weekly until low end of target, then decrease to once to twice weekly.
  • If converting from epoetin alfa to darbepoetin-divide weekly units by 400 to establish µg to give once weekly.
  • Individualize to each patient; life-long treatment required.
  • If PCV exceeds target, discontinue until upper target range is achieved, then increase dosage interval.
  • Serum iron and transferrin saturation should be normalized before initiating and during treatment. Injectable iron (10 mg/kg IM) should be administered when indicated on iron panel. Injectable iron is preferable and better tolerated than oral preparations.
  • Species-specific erythropoietins for dogs and cats are not currently commercially available.
  • Alternative erythropoietin-stimulating treatments are under development.

Anabolic Steroids

Little or no efficacy or indication for use.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • PCV-weekly to semi-monthly for 3 months, then monthly to bimonthly.
  • Blood pressure-semi-monthly to monthly.
  • Iron and transferrin saturation-at 1, 3, and 6 months, then semiannually.
  • Discontinue erythropoietin if patient develops evidence of erythrocythemia, local or systemic sensitivity, anti-r-HuEPO antibody formation, pure red cell aplasia, or refractory hypertension.

Possible Complications

Erythropoietin-Related

  • Development of erythrocythemia, seizures, hypertension, iron depletion, injection pain, and mucocutaneous reactions.
  • Development of a pure red cell aplasia during the course of epoetin alfa treatment suggests formation of anti-r-HuEPO antibodies, which neutralize r-HuEPO and native erythropoietin, causing severe anemia in 20–30% of animals; often reversible with cessation of treatment.
  • Development of anti-r-HuEPO antibodies occurs in less than 5% of patients with darbepoetin alfa therapy.
  • Signs associated with production of anti-r-HuEPO antibodies while the patient is receiving epoetin alfa include decreasing PCV, erythroid hypoplasia, absolute reticulocyte counts approaching zero, and myeloid:erythroid ratio 8.
  • Erythropoietin replacements should be used cautiously or withheld if hypertension or iron deficiency develop; treatment can be reinstituted once hypertension and iron deficiency are corrected.

Transfusion-Related

  • Incompatibility reaction
  • Circulatory or iron overload
  • Systemic hypertension
  • Transmissible infection

Expected Course and Prognosis

  • Correction of anemia increases appetite, activity, grooming, affection and playfulness, weight gain, and cold tolerance, and decreases sleeping.
  • Use of erythropoietin replacement agents in dogs and cats requires careful assessment of the risks and benefits for individual patients.
  • Short-term prognosis depends on the severity of the renal failure.
  • Long-term prognosis is guarded to poor because of the underlying chronic renal failure.

Miscellaneous ⬆

Miscellaneous

Abbreviations

  • CKD = chronic kidney disease
  • FeLV = feline leukemia virus
  • FIV = feline immunodeficiency virus
  • PCR = polymerase chain reaction
  • PCV = packed cell volume
  • RBC = red blood cell
  • r-HuEPO = recombinant human erythropoietin

Suggested Reading

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.

Cowgill LD, James KM, Lew JK, et al. Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure. J Am Vet Med Assoc 1998, 212:521–528.

Authors Sheri Ross and Ilaria Lippi

Consulting Editor Carl A. Osborne

Acknowledgment The author and editors acknowledge the prior contribution of Larry D. Cowgill.