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February 01, 2021

Creating brighter futures for cats with chronic kidney disease

Diagnostics and treatments have improved, artificial intelligence offers predictive diagnostic tool
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Cats with chronic kidney disease can now live longer, better lives than ever before.

“It’s been a very exciting time over the last decade or so in that we’ve really enhanced our abilities to diagnose and detect chronic kidney disease,” said Dr. Shelly L. Vaden, a professor of internal medicine at North Carolina State University College of Veterinary Medicine. “We’ve also made many improvements in medical management.”

Dr. Vaden was speaking during the New Therapeutic Approaches to Chronic Care Symposium at the AVMA Virtual Convention 2020 this past August. Another convention presentation focused on RenalTech, a new tool from Antech Diagnostics that uses artificial intelligence to predict which cats will develop chronic kidney disease in the next two years.

During an October 2020 webinar from Morris Animal Foundation, Dr. Jessica Quimby, an associate professor of small animal internal medicine at The Ohio State University College of Veterinary Medicine, spoke about trying to develop a deeper understanding of CKD in cats while still improving on practical aspects of treatment.

Tabby cat looking outward


A mosaic of treatment

Dr. Vaden said about 2%-20% of all cats and 30% of cats over the age of 10 have chronic kidney disease. The recent advances in diagnostics and medical management mean veterinarians can now be treating some cats for extended periods.

“When we look at that and we’re talking about treating some of these cats for three years or more, we really need to be very thoughtful in what we do and use an evidence-based approach to our treatment and diagnostics,” she said.

Chronic kidney disease is usually diagnosed via imaging or by finding persistent azotemia or an increase in serum symmetric dimethylarginine concentration. The next step is staging according to the system from the International Renal Interest Society.

Billy (right) and Amber (left)
RenalTech, a new predictive diagnostic tool from Antech Diagnostics based on artificial intelligence, predicted that Billy (above right), a neutered 12-year-old male cat, would develop chronic kidney disease in the next two years, and predicted that Amber (above left), a spayed 7-year-old female cat, would not. (Photos courtesy of Antech Diagnostics)
Sophie
Sophie lived to be 19 before dying of chronic kidney disease. She belonged to Dr. Jessica Quimby, an associate professor of small animal internal medicine at The Ohio State University College of Veterinary Medicine, who studies CKD in cats. (Courtesy of Dr. Quimby)

The IRIS stages, from 1-4, are based on serum creatinine and SDMA concentrations, the latter added recently. The staging system also offers substaging on the basis of severity of proteinuria and hypertension.

“The staging becomes important because it’s a way to communicate where we are diagnostically, where we are therapeutically, where the animal is in regards to expected progression and symptomatology,” Dr. Vaden said.

For a cat in stage 1 or early stage 2, it is important to identify and treat any underlying primary renal disease, if the veterinarian is able to identify a disease that is treatable. For a cat in late stage 2 or stage 3, Dr. Vaden starts evaluating and managing factors inherently associated with progression. For a cat in stage 4, Dr. Vaden characterizes and treats the many complications of chronic kidney disease.

“When I look at the management of chronic kidney disease, I look at it as a mosaic,” Dr. Vaden said. “Rather than one-size-fits-all, I try to identify which problems are present and then address those. And some of these problems are interrelated. So again, trying to look at those as a mosaic and trying to see what we need to address, what we can address to make an animal feel better.”

Dr. Vaden offered recommendations for controlling aspects of nutrition, proteinuria, hypertension, anemia, metabolic acidosis, renal secondary mineral disorders, hypokalemia, and gastrointestinal signs (see sidebar).

Risk factors, predictive diagnostics

A Feb. 1, 2014, JAVMA scientific article examined “Risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals.” The retrospective case-control study looked at feline patients examined at Banfield Pet Hospitals in 2010.

According to the abstract: “Risk factors for CKD in cats included thin body condition, prior periodontal disease or cystitis, anesthesia or documented dehydration in the preceding year, being a neutered male (vs spayed female), and living anywhere in the United States other than the northeast. The probability of CKD decreased with increasing body weight in nondehydrated cats, domestic shorthair breed, and prior diagnosis of diabetes mellitus and increased when vomiting, polyuria or polydipsia, appetite or energy loss, or halitosis was present at the time of diagnosis or control group inclusion but not when those signs were reported 6 to 12 months earlier. Median weight loss during the preceding 6 to 12 months was 10.8% and 2.1% in cats with and without CKD, respectively.”

Dr. Jennifer Ogeer, Antech vice president of medical affairs and commercial marketing, spoke at the AVMA Virtual Convention 2020 on “Taking the Surprise out of Chronic Kidney Disease With Artificial Intelligence.”

In October 2019, Antech announced RenalTech, a predictive diagnostic tool for chronic kidney disease in cats based on machine learning, which is a type of artificial intelligence that uses algorithms to identify patterns in data. Antech and Banfield are owned by Mars PetCare, and RenalTech was developed on the basis of data from feline patients examined over a period of 20 years at Banfield Pet Hospitals.

Details about a version of the model using four measurements—creatinine concentration, blood urea nitrogen concentration, urine specific gravity, and age—were published in the November/December 2019 issue of the Journal of Veterinary Internal Medicine. The model was able to predict CKD in cats two years before clinical diagnosis. Dr. Ogeer said co-morbidities identified as significantly associated with an increased likelihood of CKD versus no CKD were hyperthyroidism, diabetes mellitus, hepatopathy, and being underweight.

RenalTech uses additional parameters—white blood cell count, urine protein concentration, and urine pH. Dr. Ogeer said the tool predicts whether a cat will develop CKD in the next two years with more than 95% accuracy. After the tool made about 300,000 predictions for cats in the United States and Canada, Antech found the median age was 15 years for cats predicted to develop CKD within two years, while the median age was 9 years for cats predicted not to develop CKD within two years.

To make a prediction for an individual cat, RenalTech requires measurements from two visits within 24 months and more than 60 days apart. All the parameters are available from a complete blood cell count, chemistry profile, and complete urinalysis.

“RenalTech provides actionable information that enables veterinarians to formulate targeted, personalized care plans for their feline patients,” Dr. Ogeer said.

Feline Chronic Kidney Disease - Source: Dr. Shelly L. Vaden, “Feline Chronic Kidney Disease,” in Proceedings of the AVMA Virtual Convention 2020 (©2019 Boehringer Ingelheim Animal Health USA Inc., Duluth, GA. All rights reserved. US-PET-0486-2019)


Studying disease, supporting cats

The October 2020 webinar from Morris Animal Foundation was an overview of what pet owners need to know about chronic kidney disease in cats. Dr. Quimby provided commentary on future directions.

“Even though it’s a very common disease, there is actually a lot about the pathophysiology, or the disease process, that we don’t really understand for cats,” she said.

Researchers are trying to learn more about the disease process in cats, including why it starts in the first place. Dr. Quimby has been looking at the aging kidney and how it starts to malfunction.

Another thing that Dr. Quimby focuses on is nutrition: picking the best nutrition for cats with CKD and making sure the cats are actually eating the food. She and her colleagues are studying aspects of diet and of the microbiome of the intestine.

On the clinical side, Dr. Quimby emphasized the importance of getting cats with CKD to feel better. She said, “If we can’t fix the kidney disease, we want to be able to support them as much as possible.”

Dr. Quimby said appetite stimulants have been one of the most influential developments in the treatment of CKD in cats. When she worked in a feline-only practice for a couple of years, the practice started using mirtazapine as an appetite stimulant for cats with CKD. Dr. Quimby went on to lead research on how to use mirtazapine better, discovering information that supported the development of transdermal administration.

Veterinarians also are more free or encouraged now to give anti-nausea medications. Dr. Quimby said some practitioners don’t think anti-nausea medications are necessary in kidney disease, but she noted that toxins are building up in the blood and must make cats feel very ill.

A big hurdle is just getting the cat to the veterinarian. Many people have been concentrating recently on creating feline-friendly practices, implementing stress-free handling, and thinking about things from the cat’s perspective.

Giving gabapentin to cats to relieve the stress of veterinary visits has become popular, for example. Cats with CKD do need a reduced dose, which Dr. Quimby and colleagues are currently studying. Dr. Quimby said gabapentin was very helpful in the last years of the life of her own cat that had CKD.

 

The mosaic of treatment for CKD in cats

Dr. Shelly L. Vaden, a professor of internal medicine at North Carolina State University College of Veterinary Medicine, offered the following recommendations for controlling various aspects of chronic kidney disease in cats, during a session at the AVMA Virtual Convention 2020.

Nutrition: A renal diet is a cornerstone of managing CKD and can improve quality of life and prolong patient survival. Enhance the ratio of omega-3 fatty acids to omega-6 fatty acids; restrict protein, phosphorus, and sodium contents; and increase potassium, vitamin, and fiber contents and caloric density.

Proteinuria: Persistent proteinuria is associated with a greater frequency of morbidity and mortality associated with CKD. Manage with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Hypertension: Control of blood pressure is essential for CKD management, in that hypertension can cause a more rapid decline in renal function. Because amlodipine can activate the renin-angiotensin-aldosterone system, an ACEi or ARB needs to be given concurrently to block this activation. Telmisartan, an ARB, lowers blood pressure and can be used as a single agent to control hypertension in cats with CKD.

Anemia: Moderate to severe nonregenerative anemia in cats with CKD may lead to weakness, lethargy, anorexia, and cold intolerance. Eliminate ongoing blood loss, and reduce concurrent infections. When packed cell volume is less than 25%, consider iron supplementation with or without an erythropoiesis-stimulating agent.

Metabolic acidosis: Cats with CKD and metabolic acidosis will not feel well and may be anorexic. Renal diets help address acidosis. However, alkalinizing agents—sodium bicarbonate or potassium citrate—may be needed.

Renal secondary mineral disorders: Alterations in vitamin, mineral, and hormonal balances are associated with reduced survival time. Diet alone may control phosphate concentrations. Persistent hyperphosphatemia requires intestinal phosphate binders.

Hypokalemia: Low potassium causes vasoconstriction, disrupts cell functions, impairs protein synthesis, inhibits anti-diuretic hormone, and can dramatically worsen renal function. Use potassium gluconate for hypokalemia in isolation, and use potassium citrate for hypokalemia combined with metabolic acidosis.

Gastrointestinal signs: Cats with CKD have been shown to have gastric mineralization and gastric gland hypertrophy. Renal diets will help alleviate gastrointestinal signs in some cats, while others will need anti-nausea agents.