Veterinary professionals gain a better understanding of the condition’s pathogenesis and new treatment strategies
This article was updated October 19, 2023.
Up to 50% of cats will be diagnosed with chronic kidney disease (CKD) in their lifetime, and for 17% of geriatric cats, this will be the cause of death.1,2 A common comorbidity seen in 65% of these patients is anemia,3 which becomes more severe as CKD progresses and can have a significant impact on quality of life. Shelly Vaden, DVM, PhD, DACVIM, a founding member of the American College of Veterinary Nephrology-Urology, reviewed the current understanding of the pathogenesis of this anemia and available treatment options, during a session sponsored by Elanco at the 2023 Fetch Coastal conference in Atlantic City, New Jersey.4
Anemia of CKD affects patient survival and quality of life
The presence of anemia in cats with chronic kidney disease is associated with lower quality of life, more rapid progression of CKD, and shorter survival times. Clinical signs of cats with anemia of CKD include lethargy and social isolation (hiding and decreased owner interaction). Vaden has seen cats who receive treatment for their anemia have increased energy, owner interaction, and overall quality of life.4
According to Vaden, historically, “we [have delayed] treatment for a disorder that makes animals feel better once treated.” In a retrospective study of 211 cats with chronic kidney disease (serum creatinine >2.3 mg/dL) median survival from the time of diagnosis was 771 days.5 However, those cats with a packed cell volume (PCV) less than 25% had a median survival of 100 days, and for the 42 cats that received treatment for their anemia, median survival was only 25 days.5 Vaden concluded that “we are intervening late [with anemia of CKD]. Probably because we haven’t had great drug [options].”
Pathophysiology: More complex than a lack of erythropoietin
The pathophysiology of anemia of CKD is multifactorial and more complex than once thought. Traditionally, the lack of erythropoietin (EPO) production by the kidneys was assumed to be the primary mechanism. Although this is a contributing factor, proposed additional mechanisms include4:
“We can’t talk about anemia without talking about iron,” said Vaden. The iron deficiency that occurs in CKD is often thought to be a functional deficiency, meaning that iron is present in the body but is not accessible for use. Iron has many functions in the body, including red blood cell production. Iron levels are tightly regulated. One major regulator is hepcidin, a protein, which inhibits iron absorption and transport and promotes sequestration of iron in storage.4
Another consideration in the pathophysiology is worsening anemia through the use of other medications used for CKD, in particular aluminum hydroxide as a phosphate binder. “Once you get to the point of an anemic patient, I’m not sure [aluminum hydroxide] is the best choice,” said Vaden. Aluminum and iron both bind to transferrin for transport, so increased aluminum in the body can block iron transport, further exacerbating functional iron deficiency and anemia. Vaden suggested the use of ferric citrate, which serves as both a source of iron supplementation and phosphate binder, as an alternative therapy.4
Treatment with erythropoietin stimulating agents
Historically, erythropoietin stimulating agents (ESA) have been used to manage anemia of CKD. Cats treated with recombinant human EPO have shown increases in hematocrit and improved quality of life, including better appetite, energy, body condition, strength, and activity levels.6
However, Vaden noted that the risk of antibody formation and subsequent anemia is high and, therefore, using human EPO is not recommended.
Darbepoetin, a second-generation ESA, has been the preferred treatment because of its longer half-life and decreased risk of pure red cell aplasia. However, not all patients will respond, and nonresponders are more likely to have concurrent diseases.7 Adverse events in cats include vomiting, fever, and exacerbation of hypertension.7 Some seizures in cats can be caused by this hypertension. Pure red cell aplasia is rarely seen with darbepoetin use.
Vaden mentioned that a recombinant feline EPO product was being studied but is unlikely to become commercially available. New research into an adeno-associated virus vector containing the gene for feline EPO is currently under investigation and may offer a one-time treatment option.8 However, it too is associated with hypertension exacerbation and seizures.
A new medication for treating anemia of CKD in cats
A new class of drugs, hypoxia-inducible factor-prolyl hydrolase (HIF-PH) inhibitors, may offer better outcomes for anemia of CKD in cats. HIF stimulates endogenous EPO production and mobilizes iron by blocking hepcidin and increasing transferrin, a protein necessary for iron transport. The drug prevents the degradation of HIF, prolonging its effects in the body.4
Molidustat oral suspension (Varenzin-CA1; Elanco) has received conditional approval from the FDA for control of nonregenerative anemia associated with CKD in cats. It is administered by mouth once daily for up to 28 days followed by a 7-day treatment break to avoid development of polycythemia. Weekly monitoring of PCV is recommended starting 14 days after the beginning of treatment. Because the drug is conditionally approved, it may not be used off-label. The most common adverse effect is vomiting. Additionally, changes in serum potassium and exacerbation of hypertension can be seen.4
Vaden recommends iron supplementation for any patients who are being treated for anemia. While it is likely that most cats have a functional iron deficiency, this could become an absolute deficiency once iron is mobilized and utilized with treatment for anemia. It is currently difficult to accurately measure iron levels with available laboratory testing. “Right now, we treat them as if they are iron deficient,” said Vaden. Supplementation can be provided parentally or orally.4
Take home points
Anemia of chronic kidney disease is multifactorial. While treatment with erythropoietin stimulating agents has historically been used, newer medications are now available. Molidustat oral suspension is conditionally approved to control nonregenerative anemia associated with CKD in cats. Its novel mechanism promotes stimulation of endogenous erythropoietin and mobilizes iron from storage sites in the body. Regardless of how anemia of CKD is treated, Vaden encouraged veterinarians to discuss treatment with their clients as cats who are treated for their anemia have a better quality of life. Iron supplementation is encouraged as part of the treatment plan to prevent iron deficiencies from developing.4
Kate Boatright, a 2013 graduate of the University of Pennsylvania, is a practicing veterinarian and freelance speaker and author in western Pennsylvania. She is passionate about mentorship, education, and addressing common sources of stress for veterinary teams and recent graduates. Outside of clinical practice, Boatright is actively involved in organized veterinary medicine at the local, state, and national levels.