Promising new biomarkers to diagnose feline chronic kidney disease

Chronic kidney disease (CKD) is common in cats but often goes undiagnosed until it’s at a late stage. Thanks to a recent study in ACS’ Journal of Proteome Research, researchers have new leads to determine how feline CKD develops. The paper reports collections of potential protein biomarkers in urine that could help veterinarians detect different stages of the disease and develop more targeted and effective treatments for this irreversible ailment.

“The search for more precise biomarkers is not unique to feline CKD. This is a common problem in biomarker discovery across other chronic diseases.” – Katelyn Brusach

Feline CKD is an umbrella term for disorders that cause kidney damage and dysfunction, making it difficult to diagnose and treat. And because CKD is common in older cats, it can be challenging to distinguish between disease and natural decline. In some cases, definitive diagnoses may require biopsies and extensive lab workups that are invasive, time consuming, and cost prohibitive. Although blood-based biomarkers exist, they often don’t help vets uncover the root cause of the kidney dysfunction or they detect only mid- to late-stage feline CKD, leaving earlier stages undiagnosed. “The search for more precise biomarkers is not unique to feline CKD. This is a common problem in biomarker discovery across other chronic diseases,” says Katelyn Brusach, lead researcher of the study. Here, Brusach and colleagues wanted to use urine as a noninvasive sample to further characterize CKD.

The study, conducted in Jessica Quimby’s feline CKD research program at The Ohio State University College of Veterinary Medicine, analyzed urine from 30 healthy cats and 34 cats with CKD. The team identified a collection of more than 2,000 proteins in feline urine. Of those, one protein called MMP-7 showed promise as a biomarker for early-stage CKD. Its levels were higher in early-stage patients than in healthy controls.

But one biomarker doesn’t always tell the full story. “Chronic diseases are often heterogeneous, which makes them challenging to encapsulate with one protein,” says Brusach. “Therefore, we sought to utilize urinary protein profiles to measure how protein groups trend across disease.”

When they looked at groups of proteins, the researchers found three subgroups that stood out in the urine samples from cats with late-stage CKD. These subgroups could be used to help classify different types of the disease and inform treatment plans:

• One cluster was linked to cats with a stage of CKD that might be stable and not progressing.
• Another cluster included younger males with advanced proteinuric disease.
• The third cluster may indicate a more unstable late-stage disease state.

The study provides a good start toward developing new clinical biomarkers for feline CKD diagnosis and treatment. “By leveraging a deeply profiled urinary proteome, we were able to use protein profiles to measure disease differences that individual protein markers could miss,” says Brusach.

The authors acknowledge funding from Zoetis, Inc.

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