Urine ammonia ratio emerges as a prognostic biomarker for canine chronic kidney disease

Dogs with chronic kidney disease (CKD) that present with a low urine ammonia–creatinine ratio (UACR) face faster disease progression and higher case fatality than dogs with higher ratios, according to a prospective study published on May 28, 2026, in the Journal of Veterinary Internal Medicine.¹ The findings, from a team led by North Carolina State University (NC State), point to UACR as a potentially useful, noninvasive prognostic marker in naturally occurring canine CKD.²

Metabolic acidosis is a well-recognized complication of CKD, reported in up to 71% of affected dogs, and the kidney’s ability to excrete ammonia is central to maintaining acid-base balance. In human medicine, reduced urinary ammonia excretion has been linked to accelerated CKD progression and increased case fatality, but the prognostic relevance of ammonia excretion in dogs had remained unclear.¹

“In people, there’s a clear link between reduced ammonia excretion over a 24-hour period and accelerated kidney disease,” Autumn Harris, DVM, ACVIM, associate professor of nephrology-urology at NC State College of Veterinary Medicine and first author of the study, said in a news release.² “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.”²

Study design

The prospective, observational longitudinal study enrolled 50 client-owned dogs (22 female, 28 male) with International Renal Interest Society (IRIS) stage II to IV CKD that were being managed or monitored at the University of Florida and NC State. All dogs had been eating a therapeutic renal diet for at least 28 days and were classified as having stable azotemia. Most were IRIS stage II.¹

Dogs underwent baseline blood and urine sampling and were reevaluated with a serum biochemistry panel every 3 months for up to 12 months or until death. The UACR was calculated from a single baseline urine sample using a commercially available enzymatic ammonia assay and the modified Jaffe method for creatinine. Investigators stratified dogs by a UACR cutoff of less than 2.0 vs 2.0 or greater, derived from receiver operating characteristic analysis, and assessed associations with survival and progression using Cox proportional hazards and Kaplan-Meier methods. Progressive CKD was defined as a greater than 25% increase in serum creatinine from baseline.¹

Key findings

By the end of the study, 30 of the 50 dogs had died, including 17 from renal disease. Dogs with a UACR below 2.0 at enrollment had a significantly greater risk of death and a shorter median survival time of 189 days compared with 445 days for dogs with a UACR of 2.0 or greater.¹

A low UACR was also associated with faster disease progression. Dogs below the 2.0 threshold reached CKD progression at a median of 132 days vs 445 days for dogs at or above it. In the multivariable model, a UACR below 2.0 was the only variable independently associated with increased risk of death, whereas a urine protein–creatinine ratio (UPCR) below 1.0 emerged as protective.¹

Notably, only 28% of dogs met the criteria for overt metabolic acidosis at baseline, yet the UACR still predicted outcomes. The authors suggested that impaired ammonia excretion may precede measurable declines in serum bicarbonate, positioning the UACR as an earlier indicator of acid-base dysregulation than some conventional blood work.¹

“These findings indicate that UACR might serve as a clinically useful and noninvasive biomarker to identify dogs at risk of progression of their kidney disease who might benefit from early, targeted alkaline therapeutic intervention,” Harris said in the news release. “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.”²

Clinical implications

The investigators proposed that the UACR could complement UPCR and IRIS staging to guide therapeutic decision-making, potentially flagging dogs whose renal ammoniagenesis is already impaired and who might benefit from early alkali therapy, dietary modification to reduce net acid load, or more intensive monitoring. Their UPCR findings also reinforced the prognostic weight of proteinuria, with a UPCR of 1.0 or greater associated with markedly shorter survival.¹

The authors cautioned that the UACR cutoff was derived within this single cohort and should be considered exploratory and hypothesis-generating until validated in independent populations. Other limitations included a single baseline UACR measurement, clinician-dependent case management, and a relatively small number of dogs with IRIS stage IV kidney disease. The study was supported by the American Kennel Club Canine Health Foundation.¹

References

1. Harris AN, Cooper A, Castro RA, Specht AJ, Vaden SL, Cooke KL. Association of impaired ammonia excretion with survival in dogs with stable chronic kidney disease. J Vet Intern Med. 2026;40(3):aalag100. doi:10.1093/jvimsj/aalag100

2. Ammonia levels in urine could serve as marker for chronic kidney disease in dogs. News release. North Carolina State University. May 28, 2026. Accessed May 29, 2026. https://www.eurekalert.org/news-releases/1130052