# Urinary cell cycle arrest biomarkers TIMP-2 and IGFBP7 for the assessment of acute kidney injury in dogs with pyometra

## TL;DR

This study shows that TIMP-2 and IGFBP7 in dog urine can detect early kidney damage before traditional blood tests show signs, in dogs with pyometra and inflammation.

## Contribution

The study introduces urinary TIMP-2 and IGFBP7 as potential early biomarkers for acute kidney injury in dogs with pyometra and systemic inflammation.

## Key findings

- Urinary TIMP-2 and IGFBP7 correlated with increasing severity of renal injury in non-azotemic dogs.
- Conventional biomarkers like serum creatinine failed to detect early kidney injury.
- Principal component analysis confirmed the association between TIMP-2/IGFBP7 and renal lesion severity.

## Abstract

Acute kidney injury (AKI) is associated with increased morbidity and mortality and may develop secondary to systemic inflammatory conditions. Conventional biomarkers, such as serum creatinine and urinary gamma-glutamyl transferase (GGT), often fail to detect early renal injury. Cell cycle arrest biomarkers, including tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), have shown potential for early AKI detection in critically ill human patients; however, evidence in veterinary medicine remains limited. This prospective cross-sectional blinded study evaluated whether urinary TIMP-2 and IGFBP7 reflect histopathological renal injury severity in 27 clinically non-azotemic female dogs with pyometra and systemic inflammatory response syndrome (SIRS). Renal tissue samples were collected during ovariohysterectomy and graded according to tubular, glomerular and interstitial lesions. Animals were categorized as having discrete, moderate or severe injury based on cumulative lesion scores. Urinary TIMP-2 and IGFBP7, either alone or normalized to urinary creatinine, were compared with serum creatinine, symmetric dimethylarginine (SDMA) and protein-to-creatinine ratio (UPC). All dogs were non-azotemic at presentation. Tubular injury was the most prevalent histopathological finding. Conventional biomarkers did not differentiate lesion severity, whereas urinary TIMP-2 and IGFBP7 showed a significant association with increasing renal injury grade. Principal component analysis supported these findings. These results suggest that urinary TIMP-2 and IGFBP7 can detect renal lesions before azotemia and may serve as promising biomarkers for the identification of pre-azotemic renal injury in dogs with pyometra.