# Evaluation of Urinary Tubular Biomarkers in Dogs with Myxomatous Mitral Valve Disease Across ACVIM Stages

## TL;DR

This study shows that urine tests can detect early kidney damage in dogs with heart disease before blood tests show changes.

## Contribution

The study identifies urinary alkaline phosphatase and gamma-glutamyl transferase as early biomarkers for kidney injury in dogs with myxomatous mitral valve disease.

## Key findings

- Urinary alkaline phosphatase and gamma-glutamyl transferase increase in early, asymptomatic stages of heart disease in dogs.
- Urinary N-acetyl-β-D-glucosaminidase rises in dogs with heart enlargement.
- Urine biomarkers detect kidney changes before serum markers change.

## Abstract

Myxomatous mitral valve disease is the most common heart disease in dogs. Since it is a chronic cardiac disease, it can also affect the kidneys, causing cardiovascular–renal axis disorders. We evaluated whether urine tests could detect early kidney tubular injury in dogs with this disease, for which only a tubular biomarker has been described, urinary neutrophil gelatinase-associated lipocalin. We studied 84 dogs, including 20 healthy controls and 64 dogs with myxomatous mitral valve disease, across different disease stages. We measured four urine tubular biomarkers and compared them with standard serum kidney tests. Urinary alkaline phosphatase and urinary gamma-glutamyl transferase were increased even in early, asymptomatic dogs, urinary N-acetyl-β-D-glucosaminidase was higher in dogs with heart enlargement, and urinary cystatin C and serum kidney biomarkers increased mainly in clinical stages, suggesting that kidney tubular alterations can appear before changes are detected in blood biomarkers. These urine biomarkers were not associated with the diuretic treatment, which could have been a potential cause. Overall, readily available urine tests may help veterinarians detect and monitor early kidney involvement in dogs with myxomatous mitral valve disease within the cardiovascular–renal axis disorders.

Myxomatous mitral valve disease (MMVD) is the most common acquired heart valve disease in dogs and it may contribute to cardiovascular–renal axis disorders (CvRD) in dogs. Sensitive and early biomarkers of renal involvement are needed. In this prospective and observational study, 84 dogs were enrolled (20 healthy dogs and 64 dogs with MMVD), categorised using the American College of Veterinary Internal Medicine guidelines. Serum and urinary parameters were analysed, including tubular biomarkers expressed as creatinine-ratios: urinary alkaline phosphatase (uALPc), gamma-glutamyl transferase (uGGTc), N-acetyl-β-D-glucosaminidase (uNAGc), and cystatin C (uCystc). uALPc, uGGTc, and uNAGc were higher in MMVD than in controls; uALPc and uGGTc were increased from stage B1, uNAGc was higher in stages with cardiomegaly (B2 and C+D), and uCystc increased mainly in clinical stages (C+D). Serum renal markers increased only in clinical stages. ROC analysis showed good discrimination for MMVD with uALPc (AUC 0.87) and uGGTc (0.86); for cardiomegaly with uALPc (0.77) and uNAGc (0.75); and for congestive heart failure with SDMA (0.85) and uCystc (0.75). No urinary biomarker was associated with daily furosemide dose. Urinary tubular biomarkers, particularly uALPc and uGGTc, detect early CvRD in dogs with MMVD and complement traditional serum markers.