Cats that suffer from chronic kidney disease (CKD) oftentimes may also have poor appetite. Over time, this may cause poor body condition and contribute to their death. A medication called mirtazapine may help change this prognosis.
Thanks to the dedication of Jessica Quimby, DVM, PhD, DACVIM, associate professor at The Ohio State University and an affiliate professor at Colorado State University, mirtazapine is helping cats with CKD gain weight and stay healthy despite their disease. Her work over the past 10 years has paved the way for approval of a transdermal mirtazapine ointment for cats by the Food and Drug Administration that is expected in late 2017.
Although Dr. Quimby did not develop the ointment for FDA approval, she has conducted four clinical trials showing the effectiveness of mirtazapine as a tablet and transdermal gel to increase appetite in both healthy and CKD cats. “In our studies, we saw a significant increase in appetite and activity level in CKD cats that took mirtazapine compared to those that were given a placebo,” Dr. Quimby says.
“Weight gain occurred in 91 percent of cats, plus there was a statistically significant decrease in vomiting. Body condition score improved in 45 percent of cats receiving mirtazapine. Our studies showed that mirtazapine is an effective appetite stimulant and antinausea medication for cats with CKD when it is used as an adjunct to nutritional management.”
Explaining the need for the medication, Dr. Quimby says, “I was in a feline veterinary practice before moving to the university. I saw a lot of elderly cats with chronic kidney disease. The question that bothered me was, ‘What can I do to help these cats?’”
The answer came in the mirtazapine research. Dr. Quimby showed that weight gain can occur in as little as 21 days. The transdermal mirtazapine gel, an alternative to tablets, provides early intervention to offset the negative effects of CKD.
“As the kidneys begin to fail, they no longer remove toxins from the bloodstream as they should,” Dr. Quimby explains. “These toxins build up and contribute to inappetence and nausea. This limits the ability to feed these cats the therapeutic renal diets they need and to maintain adequate caloric intake. It also is challenging to maintain muscle mass and body weight in these patients.”
The latest focus of Dr. Quimby’s research is evaluating the dosing protocol for the transdermal application of the medication to the inner ear of cats with CKD. The research is funded by the Winn Feline Foundation, a nonprofit organization that funds and supports studies focusing on feline health and medical problems.
The advantage of the transdermal application is that it provides a less-stressful alternative for cats that resist taking tablet medications and may already be taking several medications due to their illness. The tablet form of mirtazapine is available in 7.5 and 15 milligrams, neither of which are user-friendly, as the recommended dose is less than 2 milligrams.
Understanding Feline CKD
CKD is a disease that affects from 30 to 80 percent of cats 10 years of age and older. It causes progressive, irreversible deterioration of kidney function. Poor body condition often relates to decreased survival.
“Any cat over age 10 is likely to develop kidney disease,” says Dr. Quimby. “The early stages of kidney disease are likely very much underdiagnosed.”
To identify cats early, she recommends biannual checkups for senior cats that include blood and urine tests. She also advises owners to have annual veterinary exams and testing for cats over 7 years of age.
Undetected kidney disease occurs partly because the signs are similar to many feline illnesses. Weight loss, lack of appetite, increased thirst and urination, lethargy, and vomiting are common signs. Because the kidneys can function adequately when one or both are impaired, cats frequently do not show signs of illness until CKD has advanced to a severe condition.
It is not known what causes CKD and many factors may contribute to its development. Concurrent conditions that exacerbate CKD include hypertension, hyperthyroidism, anemia, low potassium, and high phosphate levels.
Veterinarians diagnose CKD by testing for increased blood urea nitrogen (BUN) and creatinine concentrations and decreased urine concentration, and by palpating the kidneys, which become smaller when diseased. Urine tests can be used to learn a cat’s ability to concentrate urine, called dilute urine specific gravity, and whether the urine contains excess protein, known as proteinuria.
Early diagnosis may be possible using a new blood chemistry test that measures a marker of kidney dysfunction, symmetric dimethyarginine (SDMA). Increased SDMA molecules are detected in the blood of cats when there is a 40 percent loss of kidney function. Comparatively, creatinine, a muscle metabolism chemical waste molecule, does not accumulate in the blood until 75 percent of kidney function is gone.
Therapeutic renal diets, containing reduced amounts of high-quality protein and restricted phosphorus as well as fatty acid and antioxidant supplements, are prescribed to help manage CKD. In addition, veterinarians advise owners to try to increase their cats’ fluid intake to reduce dehydration and help the kidneys concentrate urine. Veterinarians also may need to treat anemia, hypertension, high phosphorus, urinary tract infections, and other illnesses when present.
“There’s a lot we can do to manage kidney disease,” says Dr. Quimby. “But, if a cat can’t tolerate medical treatments, its prognosis is likely much worse.”
Depending on the stage of disease when diagnosed, it’s not unusual for cats to live several years with proper monitoring of their health status and using therapies including special diets and subcutaneous fluids, as needed. Elderly cats may require treatment for other illnesses at the same time.
“Managing appetite and caloric intake is even more challenging when there are concurrent diseases,” Dr. Quimby says. “This causes us to struggle with giving multiple medications to manage several disease states, hence why the transdermal mirtazapine gel is appealing.”
The Best Dosing Protocol
At the American College of Veterinary Internal Medicine Forum, held last June in Maryland, Dr. Quimby presented highlights of the first phase of her research related to mirtazapine dosing. She reported that cats with CKD were given 3.75 milligrams of mirtazapine transdermally every other day for three weeks, showing statistically significant gains in weight, appetite, and food consumption. However, some cats experienced excessive meowing while getting the mirtazapine gel, so a lower dose is likely more appropriate.
As the second phase of this research begins, Dr. Quimby is testing the effectiveness of giving cats with CKD a transdermal dosage of 1.87 milligrams. “The idea is to find the lowest, most-effective dose and eliminate undesirable side effects,” she explains.
A Purina Veterinary Resident Research Grant funded Dr. Quimby’s first study looking at dosing protocol. The findings, published in The Veterinary Journal in September 2013, showed that cats with stable CKD given 1.88 milligrams of oral mirtazapine for three weeks had a median weight gain of 6.4 ounces.
“We had to start from square one with this research,” Dr. Quimby says. “Our earlier investigations showed us that mirtazapine was an effective appetite stimulant for cats. The goal of this study was to provide data to help direct the most effective use of the medication with the least side effects.”
The success of the medication in treating cats with CKD made Dr. Quimby a believer. “In my opinion, mirtazapine is beneficial for any chronic disease in which appetite and weight loss are a concern,” she says.
Only a few medications are effective in cats when given transdermally, thus Dr. Quimby continues to study this method of delivery. “A drug has to have specific properties so it can get across the skin barrier and be absorbed,” she says. “In addition, a transdermal drug often requires a higher dosage than the same drug given orally, though mirtazapine appears to be effective even at lower doses.”
Getting this far to improve supportive care for CKD cats took a decade. “We’ve learned a lot about CKD, but there’s a lot more to learn,” says Dr. Quimby. “Of course, I’d like to discover the cause of CKD and cure it, but we’ll have to chip away at it slowly. Everything we learn opens the door to more questions. Every study is a building block for the next study.”
Purina appreciates the support of the Winn Feline Foundation, and particularly Vicki L. Thayer, DVM, DABVP (feline), executive director, in helping to identify this topic for the Purina Pro Plan Cat Update newsletter.
Signs of Feline Chronic Kidney Disease
- Weight loss
- Lack of appetite
- Increased thirst and urination
Owners of Cats with CKD Can Help Advance Mirtazapine Research
Cats with chronic kidney disease (CKD) may be eligible to participate in a clinical trial underway at The Ohio State University and Colorado State University. The purpose of the trial is to learn more about the effectiveness of mirtazapine transdermal gel applied to the inner skin of the ear to stimulate appetite.
Participation involves bringing cats to the schools’ veterinary hospitals for three visits and administering a gel to the ear over six weeks. During the trial, cats will receive treatments with mirtazapine transdermal gel as well as a placebo gel.