Dogs with lower urine ammonia-to-creatinine ratios (UACR) may suffer from faster progression of kidney disease and higher fatality rates, according to new research from North Carolina State University. The work suggests that UACR levels may be a useful marker for identifying dogs that may benefit from certain kidney disease therapies.

To avoid confusion, it is important to clarify that UACR refers to the ratio of ammonia to creatinine in veterinary medicine, whereas in human medicine a similar term, uACR, refers to the ratio of albumin to creatinine.

In humans with chronic kidney disease, the inability to excrete acids like ammonia via urine leads to metabolic acidosis – or a build-up of acid in the body. Metabolic acidosis can be life threatening and generally leads to poorer health outcomes for patients.

“In people, there’s a clear link between reduced ammonia excretion over a 24-hour period and accelerated kidney disease,” says Autumn Harris, associate professor of nephrology-urology at NC State and first author of a study describing the research.

“However, as there isn’t a lot of information about this relationship in dogs with chronic kidney disease, we designed this study to see if UACR levels might be associated with disease progression and outcomes.” Harris began the study while an assistant professor at the University of Florida.

The research team enrolled 50 dogs (22 female, 28 male) who were being seen for management or monitoring of International Renal Interest Society (IRIS) stage 2-4 chronic kidney disease, and who had been managed with a therapeutic diet for kidney disease. The IRIS stages are based on levels of creatinine in blood serum.

The dogs underwent initial blood and urine sampling to establish baselines, then were seen four more times over a 12-month period, with samples being collected at each visit. Demographic, biochemical and outcome data were also included in the statistical analysis.

They found that dogs with a UACR below 2.0 at enrollment were three times as likely to die of renal failure, had more rapid disease progression and experienced shorter survival times overall than dogs with higher UACR values.

The researchers also found that UACR may represent an earlier marker of acid dysregulation than some traditional bloodwork markers for kidney disease, such as serum bicarbonate concentrations. In the study, most of the dogs had normal serum bicarbonate concentrations but abnormalities in UACR levels, suggesting that altered urinary ammonia excretion may occur before more obvious changes are detectable through blood tests.

“These findings indicate that UACR might serve as a clinically useful and non-invasive biomarker to identify dogs at risk of progression of their kidney disease who might benefit from early, targeted alkaline therapeutic intervention,” Harris says. “Additionally, UACR could be used to help determine the prognosis for dogs with chronic kidney disease, allowing for interventions that could improve quality of life in these animals.”

The work appears in the Journal of Veterinary Internal Medicine and was supported by the American Kennel Club Canine Health Foundation (grant #03030). Additional NC State collaborators include Rebeca Castro and Shelly Vaden. Alexis Copper, Andrew Specht and Kirsten Cooke from the University of Florida also contributed to the work.

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