Kopecny L, Palm CA, Skorupski KA, Delgado M, Rebhun RB. Risk factors associated with progressive increases in serum creatinine concentrations in cats with cancer receiving doxorubicin. J Vet Intern Med [Internet]. 2020.
Doxorubicin is one of the more commonly used chemotherapeutic drugs in veterinary medicine. It is used to treat a multitude of cancers, both alone and in combination. One of the major adverse effects of doxorubicin in cats is cumulative renal damage- ie, the propensity for cats to develop kidney disease with large total doses of medication. However, not all cats seem equally susceptible, and kidney damage may occur at different total doses in different animals.
The purpose of this study was to determine patient factors associated with the development of kidney damage in cats receiving doxorubicin chemotherapy. It was designed as a retrospective observational study of cats receiving doxorubicin therapy at a veterinary teaching hospital over a 10 year period.
Cats were included in the study if they received doxorubicin therapy and had a creatinine measured before and after therapy. Cats with renal lymphoma were excluded, as were cats with other identified causes of acute kidney injury (AKI), and cats whose creatinine increased prior to starting therapy. AKI was defined as a sustained increase in creatinine of greater than 0.3mg/dL (26.5mmol/L).
Records from 124 cats were reviewed, and 70 met enrollment criteria. The median age was 10.9 years, 56% female spayed, 43% male neutered, and 1% male intact. Cancer diagnoses included lymphoma, sarcoma, and carcinoma.
Chronic kidney disease (CKD) was diagnosed in 41% of cats prior to the initiation of therapy with doxorubicin. Of the 70 cats enrolled, 34% experienced an increase in creatinine >0.3mg/dL from baseline. In 14% of cats, this increase was >50%. In cats where creatinine increased, the mean time to increase was 119 days (Mean of 2.8 doses of doxorubicin).
Several factors were identified that were associated with an increased risk of renal toxicity during doxorubicin therapy. These included neutropenia (odds ratio 12.4), anemia (OR 4.2), and number of radiation treatments (OR 1.2). Chemotherapy protocols were also associated with the risk of renal toxicity, with animals receiving single-agent doxorubicin more likely than those receiving CHOP (OR 20.0). This may be due to the higher number of doxorubicin doses received by cats on single agent therapy.
The authors conclude that the above factors increase the risk of kidney damage in cats undergoing doxorubicin therapy. While these are god points to identify, most of them are not controllable by clinicians. As such, while they may be useful for identification and prognostication, they may not allow better targeting of therapy.
There are several limitations present to this study. Those include the fairly small sample size and retrospective nature of the study, as well as the single-center nature. Having larger numbers of cats enrolled prospectively across different geographic locations would give more relevant, generalizable data. (MRK)
Reiman RA, Mauldin GE, Mauldin GN. A comparison of toxicity of two dosing schemes for doxorubicin in the cat. J Feline Med Surg. 2008;10:324-331.